CA2473814A1 - Method and markers for the diagnosis of renal diseases - Google Patents

Abstract

The present invention relates to means and methods for the diagnosis of a renal disease, particularly to differential diagnosis. Renal diseases of particular interest in the context of the invention are IgA-nephropathy, membranous glomerulonephritis (MGN), minimal-change-disease (MCD), focal segemental glomerulosclerosis (FSGS), and diabetic nephropathy. Particularly, the method comprises (a) measuring the presence or the absence of a polypeptide marker in a urine sample, wherein the polypeptide marker is selected from the group of polypeptide markers shown in tables 1 to 22, and (b) comparing the probability of the presence of this marker in a disease patient to the probability of the presence of this marker in a control patient, wherein the individual probabilities are as indicated in the tables, and wherein (c1) if the probability of the presence of this marker in a disease patient is higher than the probability of the presence of this marker in a control patient, the presence of this marker is indicative for a higher probability of having the disease, or (c2) if the probability of the presence of this marker in a disease patient is lower than the probability of the presence of this marker in a control patient, the absence of the marker is indicative for a higher probability of having the disease.

Description

mosaiques diagnostics and therapeutics AG July ~, 2004 M62 704CA BO/mei Method and markers for the diagnosis of renal diseases The present invention relates to the diagnosis, particularly differential diagnosis, of renal diseases.
IO
The number of patients presenting with renal diseases has been increasing in the recent years. Thus, renal diseases present an increasing problem to the health system. Many renal diseases are irreversible, therefore an early diagnosis and/or a differential diagnosis of renal diseases is important. Early diagnosis and a therapy precisely tailored to each particular disease could reduce the number of patients requiring dialysis and could also reduce the high cardiovascular risk of the patients.
Currently, precise diagnosis and/or differential diagnosis relies mostly on kidney biopsies.
Although biopsies serve as the current "gold standard" in renal diagnostics, biopsies have 2o the disadvantage of being invasive and therefore being conducted only on selected patients.
Urine analysis is a different approach to diagnose renal diseases. However, currently only few parameters of urine are routinely measured, for example creatinin, urea, albumin, blood cells (such as leukocytes and erythrocytes), bacteria, sugar, urobilinogen, bilirubin and pH value. The diagnostic value of these analyses is limited, as they lack sufficient sensitivity and/or selectivity, particularly for differential diagnosis.
Several attempts have been made to analyze the proteins contained in urine.
V. Thongboonkerd et al. have used two-dimensional polyacrylarnide gel electrophoresis (2D-PAGE) in combination with matrix-assisted laser desorption ionization-time-of flight (MALDI-TOF) mass spectrometry followed by mass fingerprinting to investigate normal human urinary proteins. A total of 67 protein forms of 47 unique proteins was . identified (V. Thongboonkerd et al. (2001). Proteomic analysis of normal human urinary proteins isolated by acetone precipitation or ultracentrifugation. Kidney International, vol. 62, p.
1461- I 469).
C.S. Spahr et al. have digested the proteins contained in urine samples with trypsin and identified 751 peptides from 124 proteins by means of liquid chromatography-tandem mass spectrometry (C.S. Spahr et al. (2001). Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest. Proteomics vol. 1, p. 93-107).
1o These studies relate only to healthy individuals. The studies have not addressed the question whether alterations in presence of urinary polypeptides can bewsed for diagnosis or differential diagnosis of renal diseases.
It has been proposed to use the presence or absence of polypeptides in urine for the diagnosis of membranous glomerulonephritis (MGN) (von Neuhoff et al. (2004).
Mass Spectrometry for the Detection of Differentially Expressed Proteins: A
Comparison of Surface-Enhanced Laser Desorption/Ionization and Capillary Electrophoresis/Mass Spectrometry. Rapid Communications in Mass Spectrometry, vol. 18: 149-156).
However, samples of only 8 patients were used in the study, which was mainly concerned with the 2o comparison of different analysis methods. The actual diagnostic value of the markers has remained unclear.
Consequently, there is need for a fast and simple methods and means for diagnosis, particularly differential diagnosis, of renal diseases.
Accordingly, the object the present invention is to provide methods and means fox the diagnosis of renal diseases, particularly for differential diagnosis of renal diseases. It is an particular object of the present invention to provide methods and means for the diagnosis and/or differential diagnosis of IgA-nephropathy, which is the most common 3o glomerulopathy.
According to a first aspect of the present invention, the problem is solved by the use of the presence of at least one polypeptide marker in a urine sample for the diagnosis, preferably the differential diagnosis, of a renal disease, wherein the polypeptide marker is selected from the group of polypeptide markers as shown in table 1 to 22.

In the context of the present invention, it has been found that with the help of the polypeptide markers as shown in table 1 to 22 it is possible to reliably diagnose or differentially diagnose, respectively, different renal diseases.
The present invention has numerous advantages compared to the state of the art. First, the presence of the polypeptide markers according to the invention can be determined in urine samples. Therefore, there is no need to take biopsies. Thus, the present invention allows a simplified and fast diagnosis of renal diseases, allowing to screen patients regularly for the presence of renal diseases and to diagnose renal diseases at early stages.
Furthermore, the 1 o polypeptide markers according to the invention can be used for differential diagnosis between different renal diseases. The high number of markers identified according to the present invention allows to increase both specificity and sensitivity of diagnosis as compared to the use of only a single or a small number of markers. Also, the present invention provides methods which allow to measure said polypeptide markes without the use of specific ligands such as antibodies or aptamers.
The polypeptide markers as shown in the tables have been identified by a method, named capillary electrophoresis-mass spectrometry (CE-MS), which will be described further below. Furthermore, the method has been described in detail in von Neuhoff et al. (2004) 2o (Mass Spectrometry for the Detection of Differentially Expressed Proteins:
A Comparison of Surface-Enhanced Laser Desorption/Ionization and Capillary Electrophoresis/Mass Spectrometry. Rapid Communications in Mass Spectrometry, vol. 18: 149-156).
Starting from the parameters defining the polypeptide markers, it is possible by methods known in the art to identify the sequence of the corresponding polypeptides and then to synthesize or produce the corresponding polypeptides, e.g. with the help of protein synthesis or expression of the corresponding gene in appropriate cells.
The markers are defined by there mass and their migration time in capillary electrophoresis (CE), particularly mass and their migration time obtained according to Example 1. It is 3o known that CE migration times can vary, typically in the range of 5 min, more typically in the range of 3 minutes. However, the sequence of markers being eluted is typically the same or very similar for each CE system applied. The system can be calibrated by use of polypeptides which are present in almost any urine sample, e.g. by the polypeptides given in tables 23 or 24. Furthermore, the polypeptides given in SEQ IZ? NO: 1 to SEQ ID NO: 5 can serve for calibration.

Variation of the masses between measurements or between different mass spectrometers is relatively small, typically it is in the range of plus or minus 0.05%.
In table l, polypeptide markers are listed which are preferred for the discrimination between healthy individuals and individuals suffering from a renal disease, particularly from a glomerulonephritis or glomerulopathy.
In table 2, polypeptide markers are listed, which are preferred for a discrimination between FSGS and the healthy condition.
io In table 3, polypeptide markers are listed, which can be used for differential diagnosis between FSGS and MCD.
In table 4, polypeptide markers are listed, which are preferred for a differential diagnosis of FSGS and MGN.
In table 5, polypeptide markers are listed, which are preferred for a differential diagnosis between FSGS on the one hand, and MCD or MGN on the other hand.
In table 6, polypeptide markers are listed, which are preferred for diagnosis of MCD as compared to the healthy condition.
In table 7, polypeptide markers are listed, which are preferred for differential diagnosis between MCD and MGN.
In table 8, polypeptide markers are listed, which are preferred for differential diagnosis between MCD on the one hand, and FSGS or MGN on the other hand.
In table 9, polypeptide markers are listed, which are preferred for diagnosis of MGN as 3o compared to the healthy condition.
In table 10, polypeptide markers are listed, which are preferred for differential diagnosis between MGN on the one hand, and FSGS or MCD on the other hand.
In table 1l, polypeptide markers are listed, which are preferred for diagnosis of IgA-nephropathy or MGN on the one hand as compared to the healthy condition.

- S -In table 12, polypeptide markers are listed, which are preferred for diagnosis of IgA-nephropathy as compared to the healthy condition.
In table 13, polypeptide markers are listed, which are preferred for differential diagnosis between IgA-nephropathy and MGN.
In table 14, polypeptides are fisted with their respective frequency in healthy, FSGS, MCD, and MGN patients.
1o In table 1 S, polypeptides are listed which have been used for differential diagnosis between healthy individuals and renal patients using support vector machines according to Example 1.
In table 16, polypeptides are listed which have been used for differential diagnosis between healthy, FSGS, MCD, and MGN patients using random forest analysis according to Example 1.
In table 17, polypeptides are listed which have been used for differential diagnosis between MCD and MGN patients using using support vector machines according to Example 1:
In table 18, polypeptides are listed which have been used for differential diagnosis between MCD and FSGS patients using using support vector machines according to Example I .
In table I9, polypeptides are listed which have been used for differential diagnosis between MGN and FSGS patients using using support vector machines according to Example 1.
In table 20 and 21, polypeptides are listed which have been identified in von Neuhoff et al.
(2004), which has been cited above. .
3o In table 22, polypeptides are listed which can be used for diagnosis of diabetes and/or diabetic nephropathy.
In table 23, polypeptides are listed, which are preferred as internal standards to standardize the CE-time.

In table 24, polypeptides are listed, which are preferred as internal standards to standardize the CE-time if the pressure method (0.3 to 1 psi) according to Example 1 is used. These standards are e.g. preferred as internal standards in diagnosis of IgA-nephropathy.
In table 2S, clinical data of renal patients are listed whose samples were used for identification of polypeptide markers according to Example 1. Abbreviations:
CsA, .
Cyclosporin A; PS , prednisolone; +, frequent relapse; -, currently no immunosuppression;
~, clinically unclear whether MCD or FSGS.
to The polypeptide maxkers used according to the present invention can be identified and their presence can be measured in urine samples. Urine samples can be taken as known in the state of the art. Preferably, midstream urine is used in the context of the present invention.
The polypeptide markers used according to the present invention can be gene expression products such as proteins, peptides, and fragments or other degradation products . of proteins or peptides. They carp be modified by posttranslational modifications, e.g. by glycosylation, phoshorylation, alkylation or disulfide bond. It is known that fragments and degradation products can have a different diagnostic value and/or physiological role than 2o the protein or peptide they have been derived from. For example, in different diseases, different proteolytic degradation products or fragments can be found. It is also considered to be within the scope of the present invention if the urine sample is pretreated to chemically modify the polypeptide markers contained in the urine and to measure these chemically modified polypeptide markers. The polypeptide markers according to the present invention have a molecular mass between 400 and 20 000 Da, particularly between 700 and 14000 Da, more particularly between 800 and 11000 Da.
Preferred polypeptide markers according to the present invention are listed in tables 1 to .
22, particularly in tables 1 to 21, more particularly in tables 1 to 13.
3o Preferred polypeptides for use as internal standards are listed in tables 23 to 24.
Preferred are also polypeptide markers which are listed in table 1, but not in table 14 and/or 15 and/or 16 and/or 17 andlor 18 and/or 19 and/or 20 andlor 21 and/or 22.
Preferred are also polypeptide markers which axe listed in table 2, but not in table 14 and/or 15 andlor 16 and/or 18.
Preferred are also polypeptide markers which are listed in table 3, but not in table 14 and/or 16 and/or 18.

_ 7 -Preferred are also polypeptide markers which are listed in table 4, but not in table 14 and/or 16 and/or 19.
Preferred are also polypeptide markers which are listed in table 5, but not in table 14 and/or 16 and/or 18 and/or 19.
Preferred . are also polypeptide markers which are listed in table 6, but not in table 14 and/or 16.
Preferred are also polypeptide markers which are listed in table 7, but not in table 14 and/or 16 and/or 17.
Preferred are also polypeptide markers which are listed in table 8, but not in table 14 l o and/or 16.
Preferred are also polypeptide markers which are Listed in table 9, but not in table 14 and/or 16 and/or 20 andlor 2I .
Preferred are also polypeptide markers which are listed in table 10, but not in table 14 and/or 16.
Preferred are also polypeptide markers which are listed in table 11, but not in table 14 andlor 16.
Renal disease according to the present invention relates to any kind of renal disease or kidney dysfunction known to the person skilled in the art, for example IgA-nephropathy, 2o MGN (membranous glomerulonephritis), MCD (minimal-change disease), FSGS
(focal-segmental glomerulosclerosis), or diabetic nephropathy. Particularly, renal disease relates to a glomerulopathy such as IgA-nephropathy, MGN, MCD, or FSGS. Even more particularly renal disease relates to IgA-nephropathy, MCD, or FSGS. Most particularly, renal disease relates tn IgA-nephropathy The glomerulopathies are a subgroup of renal diseases. Glomerulopathies comprise a several diseases of different etiology. Glomerulopathies are characterized by pathomorphological changes in rnalpighian corpuscles, glomerulus, and Bowman's _ capsule. As a consequence of these changes, further pathomorphological changes may 3o appear in other parts of the nephron and interstice.
IgA-nephropathy is also known as Berger-Nephritis. IgA-nephropathy is the most common glomerulopathy. It may be a specif c, kidney-limited, form of purpura Schoenlein-Henoch (also known as anaphylactoid purpura) with increased plasma concentration of IgA. The 3s histopathology includes all forms of glomerular lesions and deposits of IgA
in the mesangium. Clinically, IgA nephropathy presents as micro- and macro-hematouria.
Therapy may be attempted with ACE inhibitors and omega-3 fatty acids.
Progression of , _ $ _ the disease occurs over the course of several years and includes transition into progressive renal insufficiency.
MGN is characterized by thickening of the basal membrane and granular subepithelial IgG
s deposits. MGN becomes frequently manifest in the between the age of 40 and 50. It is frequently caused by medicaments, e.g. gold, D-penicillamine, or ACE
inhibitors. Therapy of MGN may be attempted with glucocorticoids or cyclophosphamide. MGN is a nephrotic syndrome, a transition into progressive renal insufficiency may take several years.
1o MCD is also known as lipoid nephrosis. MCD is the most common cause of a nephrotic syndrome in children. The etiology of the disease is unknown. Histologically, no or only very discrete changes can be found. Therapy of MCD may include treatment with glucocorticoids, , cyclosporin A, or cyclophosphamide. In children, the disease spontaneously heals in 90% of the cases, in adults in 50% of the cases. A
transition into 15 FSGS is possible.
FSGS is also known as IgM-nephropathy. FSGS is typically characterized by deposits of IgM and C3 in the mesangium. Clinically, it becomes manifest as a nephrotic syndrome.
Therapy of FSGS may include treatment with glucocorticoids, cyclosporin A; or 2o cyclophosphamide._ Prognosis is poor and includes transition into progressive renal insufficiency.
Diabetic nephropathy is also known as diabetic glomerulosclerosis. Diabetic nephropathy is the most common cause for requirement of dialysis treatment.
In summary, it is evident that renal diseases include a variety of diseases which may show quite similar histology. However, etiology, treatment, and prognosis can be quite different for each disease. For example, IgA-nephropathy requires different treatment from any other glomerulopathy described above: In IgA-nephropathy, treatment with ACE
inhibitors 3o may be attempted, which would not be recommendable in the case of MGN.
Therefore, fast and reliable diagnosis is of great importance for treatment.
In the context of the present invention, diagnosing or diagnosis means that, for an individual patient, the probability of having the.respective disease is determined.
Diagnosis may also include confirming a preliminary diagnosis, particularly a preliminary diagnosis established by a different method.

Furthermore, in a preferred embodiment, diagnosis according to the present invention particularly relates to "differential diagnosis". The term "differential diagnosis" relates to distinguishing between two different diseases, i.e. to determining for an individual patient the probability of having a certain first disease as compared to having a certain second disease. More particularly, differential diagnosis according to the present invention relates to distinguishing between at least two renal diseases chosen from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.
In another embodiment; the present invention relates to a method for the differential diagnosis of a renal disease, the method comprising:
a) measuring the presence or the absence of a polypeptide marker in a urine sample, wherein the polypeptide marker is selected from the group of polypeptide markers shown in table 1 to 22, and b) comparing the probability of the presence of this marker in a disease patient to the probability of the presence of this marker in a control patient, wherein 2o cl) if the probability of the presence of this marker in a disease patient is higher than the probability of the presence of this marker in a contral patient, the presence of this marker is indicative for a higher probability of having the disease rather than the control condition, or c2) if the probability of tlae presence of this marker in a disease patient is lower than the probability of the presence of this marker in a control patient, the absence of the marker is indicative for a higher probability of having the disease rather than the control condition.
3o Preferably, the individual probabilities according to step b) are as indicated in the tables.
The term '°measuring" according to the present invention relates to determining the presence of a polypeptide or other substance of interest.
The decision whether a polypeptide marker is present or absent may depend on definition of a suitable threshold value. The threshold value can either be defined through the sensitivity of the method of measurement, or it can be defined at will. The threshold in the context of the present invention is 25 finol/~.l in a sample which has been injected into a mass spectrometer according to Example 1. However, this threshold may be the same when other methods are used. This threshold coincides with the detection threshold of a typical mass spectrometer. This threshold corresponds approximately to a concentration of the polypeptide marker in the urine sample of 50-5000 pmol/l. If different thresholds are to be used (e.g. when using another detection method), the corresponding probabilities may differ, but can easily be established by the person skilled in the art.
The "disease patient" according to the present invention is suffering from a renal disease.
to Particularly, the disease is at least one from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.
The "control patient" can either be healthy or suffering from a disease different from the one the disease patient is suffering from, i.e. the control patient can either represent the healthy condition or a disease or group of diseases. Particularly, the represented disease is at least one from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.
Tables 1 to 14, 16, 20, 21, and 22 list the probability (also designated as "frequency") of a 2o given polypeptide marker being present in a urine sample of a healthy control patient or a control patient suffering from a certain disease. The discrimination factor indicates the difference between the probability of presence in the disease as compared to a given control condition. The discrimination factor can easily be calculated from the respective probabilities. The higher the discrimination factor, the better is the potential of the given marker to distinguish between the disease and the control condition. An absolute value of the discrimination factor of 0.40 or higher is preferred.
The person skilled in the art is able to establish similar tables for the polypeptide. markers by himself and/or to refine the data contained in the tables, e.g. based on further patient 3o data and/or according to different thresholds for the presence of the polypeptide marker.
For diagnosis, the probability of the presence of the polypeptide marker in a disease patient is compared to the probability of the presence of this marker in a control patient, wherein the individual probabilities are as indicated in the tables. If the probability of the presence of this marker in a clisease patient is higher than the probability of the presence of this marker in a control patient, then the presence of this marker in the sample is indicative that the patient from whom the sample originates has a higher probability of having the disease rather than the control condition. If the probability of the presence of this marker in a disease patient is lower than the probability of the presence of this marker in a control patient, then the absence of this marker in the sample is indicative that the patient from whom the sample originates has a higher probability of having the disease rather than the control condition.
For example, a given marker may have a probability of 73% of being present in a control representing IgA-nephropathy but a probability of 0% of being present in a control representing the healthy condition. If this marker is present in the sample, then the individual is diagnosed as having a 73% probability of suffering from IgA-nephropathy as compared to being healthy. If this marker is not present in the sample, then the individual is diagnosed as having a 73% probability of being healthy instead of suffering from IgA-nephropathy.
is Thus, diagnosis can be established according to statistical methods familiar to the 'person skilled in the art.
The invention can be carried out using only one of the polypeptide markers or using a plurality of the polypeptide markers. Preferably, presence of a plurality of polypeptide 2o markers is measured. Preferably at least 3 of the markers, more preferably at least 10 of the markers, even more preferably at least 20, most preferred at least 50 of the markers according to the present invention are measured.
An advantage of the present invention is that it provides a multitude of suitable markers.
25 Measuring a plurality of marker can increase both sensitivity and selectivity of diagnosis.
Therefore, also markers which show low discrimination factors between the disease and control can be used for diagnosis if they are combined with other markers.
If a plurality of polypeptide markers is used, a "pattern" is be generated which contains the 3o information about the presence for each marker measured. This pattern can then be compared to the pattern of probabilities of presence of the polypeptide markers in a disease or control patient. Each table represents a pattern of probabilities of finding given polypeptide markers in certain disease and control patients.
35 Therefore, in a preferred embodiment, the present invention relates to a method for the differential diagnosis of a renal disease, the method comprising:

a) establishing a pattern of presence or absence for a plurality of palypeptide markers in a urine sample, wherein at least one polypeptide marker is selected from the group of polypeptide markers shown in table 1 to 22, and b) comparing the probability of finding this pattern in a disease patient to the probability of finding this pattern in a control patient, wherein cl) if the probability of finding the pattern in a disease patient is higher than the probability of the finding the pattern in a control patient, finding this pattern is indicative for a higher probability of having the disease rather than the control condition, or c2) if the prabability of finding the pattern in a disease patient is lower than the probability of the finding the pattern in a control patient, finding this pattern is indicative for a lower probability of having the disease rather than the control condition, or -Preferably, the individual probability for the at least one polypeptide marker according to step b) is as indicated in the tables.
Comparison of the found pattern with the probability of finding the pattern in a disease or control patient can be performed according to statistical mefhods known in the art.
Preferably, automated methods are employed, e.g. CART-analysis, random forest analysis, and support vector machines (SVM, see e.g. Xiong. M., et al. (2001). Biomarker identification by feature wrappers. CJenome Research vol. 11, p. 1878-1887).
Comparison can also be performed simultaneously for several different patterns and the probability of finding them.
Thus, the measured pattern is typically compared to the probability of finding the pattern in at least two different conditions. An example for diagnosis and differential diagnosis of renal diseases according to this method is shown in Fig. 3.
If necessary, the urine samples may be pre-treated before measurement of the palypeptide marker. Particularly, lipids, nucleic acids or polypeptides may be purified from the sample according to methods known in the art, including filtration, centrifugation, or extraction methods such as chloroform/phenol extraction.

Measuring the presence of a polypeptide marker can be done by any method known in the art.
Preferred methods include gas phase ion spectrometry, such as laser desorption/ionization mass spectrometry, surface enhanced laser desorption/ionization time-of flight mass spectrometry (SELDI-TOF MS) and CE-MS. These spectrometry methods allow to measure the polypeptide markers without the need for ligands such as antibodies or aptamers.
to Urine sample generally are highly complex, i.e. they contain numerous polypeptides. In case of high complexity, a spectrometric analysis becomes difficult. To reduce the complexity of the sample, the polypeptides contained in the sample may be separated by any suitable means, e.g. by electrophoretic separation, affinity-based separation, or separation based on ion exchange chromatography. Particular examples include gel electrophoresis, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), capillary electrophoresis, metal-affinity chromatography, immobilized metal-affinity chromatography (IMAC), affinity chromatography based on lectins, liquid chromatography, high pressure liquid chromatography (HPh,C), and reversed-phase HPLC, cation exchange chromatography, and selectively binding surfaces (such as the surfaces used in SELDI-TOF, see below).
2D-PAGE is commonly used for polypeptide separation aaad can be combined with mass spectrometry (MS) yielding identification of individual polypeptides. Over 1000 protein spots can be discerned with 2D-PAGE. However, each single spot must be analysed separately by MS/MS for identification.
SELDI (surface enhanced laser desorption/ionization) time-of flight mass spectrometry is currently applied in many fields of biomedical sciences.
3o In the SELDI system, the ProteinChip Arrays are the most important component. They are narrow metal strips carrying 8 or 16 spots in a row on the surface. Samples to be analyzed are directly applied to the spots, either as a standing drop or in volumes up to 500 ~1, by using sample holders called "bioprocessors" as supporting units. They are placed onto the arrays during incubation and washing steps and removed again afterwards. The different types of arrays belong to two main series: chromatographic arrays, presenting hydrophobic, hydrophilic, canon-exchanging, anion- exchanging or immobilized metal ion affinity-surfaces, and preactivated arrays with chemical groups to allow the covalent coupling of proteins. Preferably, a chip with ration-exchange surfaces is used. As the ProteinChip Arrays do not only support the sample but specifically interact with the biomolecules, the composition of the analyte depends on the array type used and the washing conditions applied. This explains why the SELDI-process can be defined as a further development of the traditional MALDI (matrix assisted laser desorption /
ionization)-technique. In the SELDI-process, only on those polypeptides are measured that actually bind to the chip surface.
1o After binding of sample proteins, the energy absorbing matrix is applied to each spot. The matrix rapidly crystallizes and the analysis can start immediately.
The ProteinChip Arrays are placed into the ProteinChip Reader for analysis.
The reader is a TOF (time-of flight) mass spectrometer in which the proteins are desorbed and ionized with the help of a laser beam. As the crystallized proteins are equally distributed on the spot surface, the ionizing laser beam always hits a representative average of the molecules in the analyte, allowing quantitative calculations. After ionization, the proteins are accelerated by an electric field to fly down the flight tube, before reaching the detector.
The flight time between the laser striking the array surface and the molecules reaching the 2o detector at the end of the flight tube enables the system to accurately determine the mass of the protein species present in the sample (for more detailed information on the method see the following review: Merchant: M and Weinberger SR (2000). Recent advancements in surface-enhanced laser desorption / ionization - time of flight mass spectrometry.
Electrophoresis vol. 212, p. 1164-1177).
However, the most preferred method is CE-MS, in which capillary electrophoresis (CE) is coupled to mass spectrometry (.MS). CE-MS has been described in detail elsewhere (see e.g. German patent application DE 100 21 737, and Kaiser, T., et al., Capillary Electrophoresis coupled mass spectrometry to establish polypeptide patterns in dialysis 3o fluids. J Chromatogr A, vol. 1013, p. 157-171(2003)).

CE is known to the person skilled in the art. In brief, the sample is loaded onto an electrophoresis capillary and a voltage of up to 50 kV, typically up to 30 kV, is applied.
Typical capillaries are fused silica capillaries, i.e. glas capillaries comprising an outer sheath as mechanical support and to improve mechanical flexibility, e.g. a sheath made of thermoplastic material. Typically, the capillary is untreated, i.e. it shows hydroxy-groups on its inside. However, the capillary may also be coated on the inside. E.g., hydrophobic coating can be used to improve discriminatory power. In addition to the voltage, also pressure may be applied, which is typically in the range of 0 to 1 psi. The pressure can also be applied or increased during the run.
to To improve discriminatory power, also a stacking protocol can be applied when loading the sample: Before loading of the sample, a base is loaded, then the sample is loaded, then an acid. The principle is to capture the analyte ions between a base and an acid. If voltage is applied, the positively charges analyte ions move towards the base. There, they get negatively charged and move into the opposite direction towards the acid, where they get positively charged. This stacking repeats itself until acid and base are neutralized. Then, the separation starts from a well concentrated sample.
The sample is contained in an appropriate buffer in which polypeptides are soluble, e.g.
2o phosphate buffer. For CE-MS coupling, it is preferred to use volatile solvents and to work under mostly salt-free conditions to avoid contamination of the =MS. Examples comprise acetonitrile, isopropanol, methanol, and the like. The solvents can also be combined with water and a weak acid (e.g. 0.1% formic acid), the latter to protonate the analyte. The polypeptides in the sample are separated according to size and charge, which determine the run-time in the capillary. CE is characterized by high separating power and short time of analysis.
For subsequent MS analysis, either fractions collected from the CE can be analyzed as separate batches or, preferably, the CE system can be coupled via a suitable interface to the 3o mass spectrometer to allow continous flow analysis. Alternatively, the flow from the CE
may be used to generate continuous "separation tracks", which can be analyzed separately.

In the mass spectrometer, ions generated from the sample are analyzed according to the mass/charge (m/z) quotient. Using mass spectrometry, it is possible to routinely analyze 10 finol (i.e. 0.1. ng of a 10 kDa polypeptide) with a precision of ~ 0.01%.
Experimentally, it is possible to analyze even less than 0.1 finol.
Any type of mass spectrometer can be used. In mass spectrometers, an ion-generating device is coupled with an suitable analyzer. For example, the electrospray ionization (ESI) interfaces are most commonly used to produce ions from liquid samples, whereas MALDI
is most commonly used to produce ions from individually processed samples.
Different 1o kinds of analyzers are available, e.g. ion trap analyzers or time-of flight (TOF) analyzers.
Both ESI and MALDI can be combined with essentially all types of mass spectrometers, although ESI has usually been combined with ion traps, whereas MALDI has usually been combined with TOF.
A preferred CE-MS method according to the present invention includes capillary electrophoresis coupled online via ESI to a TOF analyzer.
The CE-MS technique permits to measure the presence of several hundred polypeptide markers simultaneously in a short time in a small volume with high sensitivity. Once the 2o presence of the polypeptide markers has been measured, a pattern of the measured polypeptide markers is generated and can be compared to a disease pattern by any of the methods described further above. However, in many cases it will be sufficient for diagnosis to measure only one or a limited number of the markers.
~ The polypeptide sequences can be determined according to methods well-known to the person skilled in the art (see e.g. C.S. Spahr et al. (2001). Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest. Proteomics vol. l, p. 93-107).
3o Depending on the type of polypeptide marker, it is possible to measure its presence or absence by further means. For example, if the polypeptide is biologically active, its presence may be determined by cellular or enzymatic assays.

f Presence of a polypeptide earl also be determined by ose of ligands binding to the polypeptide of interest. Binding according to the present invention includes both covalent and non-covalent binding.
s A ligand according to the present invention can be any peptide, polypeptide, nucleic acid, or other substance binding to the polypeptide of interest. It is well known that polypeptides, if obtained or purified from the human or animal body, can be modified, e.g.
by glycosylation. A suitable ligand according to the present invention may bind the polypeptide also via such sites.
1o Preferred ligands include antibodies; nucleic acids, peptides or polypeptides, and aptamers, e.g. nucleic acid or peptide aptamers. For many polypeptides, suitable ligands are commercially available. Furthermore, methods to generate suitable ligands are well-known in the art. For example, identification and production of suitable antibodies or aptamers is 15 also offered by commercial suppliers.
The term "antibody" as used herein includes both polyclonal and monoclonal antibodies, as well as fragments thereof, such as Fv, Fab and F(ab)2 fragments that are capable of binding antigen or hapten.
Preferably, the ligand should bind specifically to the polypeptide to be measured. "Specific binding" according to the present invention means that the ligand should not bind substantially to ("cross-react" with) another polypeptide or substance present in the sample investigated. Preferably, the specifically bound protein or isoform should be bound with at least 3 times higher, more preferably at least 10 times higher and even more preferably at least 50 times higher affinity than any other relevant polypeptide.
Non-specific binding may be tolerable, particularly if' the investigated peptide or polype;ptide can still be distinguished and measured unequivocally, e.g.
according to its 3o size on a Western Blot, or by its relatively higher abundance; in the sample.
A method for measuring the presence of a polypeptide of interest may comprise the steps of (a) contacting a polypeptide with a specifically binding ligand, (b) (optionally) removing non-bound ligand, (c) measuring the presence or amount of bound ligand.

- 1g -Binding of the ligand can be measured by any method known in the art: First, binding of a ligand may be measured directly, e.g. by NMR or surface plasmon resonance.
Second, the ligand also serves as a substrate of an enzymatic activity o~f the peptide or polypeptide of interest, an enzymatic reaction product may be measured (e.g. the presence of a protease can be measured by measuring the amount of cleaved substrate, e.g. by Western Blot).
Third, the ligand may be coupled covalently or non-covalently to a label allowing detection and measurement of the ligand.
1 o Labeling may be done by direct or indirect methods. Direct labeling involves coupling of the label directly (covalently or non-covalently) to the ligand. Indirect labeling involves binding (covalently or non-covalently) of a secondary ligand to the first ligand. The secondary ligand should specifically bind to the first ligand. Said secondary ligand may be coupled with a suitable label and/or be the target (receptor) of tertiary ligand binding to the secondary ligand. The use of secondary, tertiary or even higher order ligands is often used to increase the signal. Suitable secondary and higher order ligands may include antibodies, secondary antibodies, and the well-known streptavidin-biotin system (Vector Laboratories, Inc.) 2o The ligand or substrate may also be "tagged" with one or more tags as known in the art.
Such tags may then be targets for higher order ligands. Suitable tags include biotin, digoxygenin, His-Tag, Glutathion-S-Transferase, FLAG, GFP, myc-tag, influenza A virus haemagglutinin (HA), maltose binding protein, and the like. In the case of a peptide or polypeptide, the tag is preferably at the N-terminus and/or C-terminus.
' Suitable labels are any labels detectable by an appropriate detection method.
Typical labels include gold particles, latex heads, acridan ester, luminol, ruthenium, enzymatically active labels, radioactive labels, magnetic labels ("e.g. magnetic beads", including paramagnetic and superparamagnetic labels), and fluorescent labels.
Enzymatieally active labels include e.g. horseradish peroxidase, alkaline phosphatase, beta-Galactosidase, Luciferase, and derivatives thereof. Suitable substrates for detection ° -19-include di-amino-benzidine (DAB), 3,3'-5,5°-tetramethylbenzidine, NBT-BCIP (4-vitro blue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl-phosphate, available as ready-made stock solution from Roche Diagnostics), CDP-StarTM (Amersham Biosciences), ECFTM (Amersham Biosciences). A suitable enzyme-substrate combination may result in a colored reaction product, fluorescence or chemoluminescence, which can be measured according to methods known in the art.
Typical' fluorescent labels include fluorescent proteins (such as GFP and its derivatives), Cy3, CyS, Texas Red, Fluorescein, the Alexa dyes (e.g. Alexa 568), and quantum dots.
to Typical radioactive labels include 355 l2sh 3zP~ 33P~ and the like.
Thus, suitable measurement methods according the present invention also include precipitation (particularly immunoprecipitation), electrochemiluminescence (electro-generated chemiluminescence), RIA (radioimmunoassay), ELISA (enzyme-linked immunosorbent assay), sandwich enzyme immune tests, electrochemiluminescence sandwich immunoassays (ECLL~), dissociation-enhanced lanthanide fluoro immuno assay (DELFIA), scintillation proximity assay (SPA), turbidimetry, nephelometry, latex-enhanced turbidimetry or nephelometry, or solid phase i~:nmune tests. Further methods 2o known in the art (such as gel electrophoresis, 2D gel electrophoresis, SDS
polyacrylamide gel electrophoresis (SDS-PAGE), Western Blotting), can be used alone or in combination with labeling or other detection methods as described above.
The ligand may also be present on an array. Said array contains at least one additional ligand, which may be directed 'against a peptide, polypeptide or a nucleic acid of interest.
Said additional ligand may also be directed against a peptide, polypeptide or a nucleic acid of no particular interest in the context of the present invention. Preferably, ligands for at least five, more preferably at least 10, even more preferably at least 20 polypeptide markers according to the present invention are contained on the array.
According to the present invention, the term "array" refers to a solid-phase or gel-like carrier upon which at least two compounds are attached or bound in one-, two-or three-dimensional arrangement. Such arrays (including "gene chips", "protein chips", antibody arrays and the like) are generally known to the person skilled in the art and typically generated on glass microscope slides, specially coated glass slides such as polycation-, nitrocellulose- or biotin-coated slides, cover slips, and membranes such as, for example, membranes based on nitrocellulose or nylon.
The array may include a bound ligand or at least two cells expressing each at least one ligand.
1o It is also contemplated to use "suspension arrays" as arrays according to the present invention (Nolan JP, Sklar LA. (2002). Suspension array technology: evolution of the flat-array paradigm. Trends Biotechnol. vol. 20(1), p: 9-12). In such suspension arrays, the carrier, e.g. a microbead or microsphere, is present in suspension. The array consists of different microbeads or microspheres, possibly labeled, carrying different ligands.
The invention further relates to a method of producing arrays as defined above, wherein at least one ligand is bound to the carrier material in addition to other ligands.
Methods of producing such arrays, for example based on solid-phase chemistry and photo-labile protective groups, are generally known (US 5,744,305). Such arrays can also be brought into contact with substances or substance libraries and tested for interaction, for example for binding or change of conformation. Therefore, arrays comprising a polypeptide marker according to the present invention may be used for identifying ligands binding specifically to said peptides or polypeptides.
To determine the sequence of .a polypeptide, it should be purified to the highest level achievable. However, the polypeptide does not need to be completely isolated.
For example, it is enough to have the polypeptide detectable as a coomassie-stained band in a polyacrylamide gel. The corresponding gel piece can then be cut out and used for the next 3o identification steps. After purification of the polypeptide, it can be;
enzymatically digested with trypsin and the molecular weights of the resulting fragments determined using any suitable method, for example mass spectrometry. Using mass spectrometry, each polypeptide displays a characteristic "fingerprint" of fragments allowing its identification by database searches. In case that the polypeptide to be identified is not present in the database or if the researcher wants to have a closer characterization for any reasons, the polypeptide fragments can also be sequenced according to methods known in the art.
CE-MS allows particularly easy determination of the polypeptide sequences. The capillary electrophoresis elution time for each marker is listed in the tables. Thus, it is possible to collect the fraction containing the polypeptide at relatively high purity. If a single fraction contains insufficient material, fractions of more than one experiment may be pooled.
1o Sequences of some of the polypeptide markers are listed as SEQ ID NO: 1 to 5. Their masses as measured by CE-MS and their respective sequences are as follows:
SEQ mass sequence description ID NO: [Da]

1 8765,9 FTFHADICTLSEKERQIKKQTALVEL fragment of human albumin, C-terminus VKHKPKATKEQLKAVMDDFAAFV amino acids 531-609.

EKCCKADDKETCFAEEGKKLVAAS

QAALGL

2 10046,3 TYVPKEFNAETFTFHADICTLSEKER ft'agment of human albumin, C-terminus, QIKKQTALVELVKHKPKATKEQL:KA wino acids 520 to VMDDFAAFVEKCCKADDKETCFAE 609.

EGKKLVAASQAALGL

3 950.0 GGRPSRPPQ fragment of Salivary proline-rich protein 4 1292.5 GFRHRHPDEAA fragment of alpha fibrinogen 5 1448.8 GLITLIGINPSLHT fragment of olfactory receptor 8B4 Figure legends:
Fig. 1 Depiction of the information from a crude CE-~MS analysis (A) as a three dimensional contour plot (left side). Here a contour plot of urine from a healthy volunteer is shown, mass per charge on the Y-axis a gainst the retention time in min (X-axis), signal intensity colour coded. Next, the signal to noise is calculated and 2o the noise removed, thus leaving only actual signals (B). The software calculates the actual mass (C) based on both isotopic distribution and conjugated masses.
This results in a table of up to 1500 polypeptides defined via their mass and retention time. As an example, bottom right shows 17 polypel9tides found in the sample.
CE-t, CE-time (migration time) ; int., intensity; m.p.c., mass per charge, cal.
m., calculated mass.
Fig. 2 Contour plots of polypeptides (actual masses) for healthy subj ects (NC) and for patients with focal-segmental glomerulosclerosis (FSGS), minimal-change disease (MCD) and membranous glomerulonephritis (MGT are shown. The upper mass limit for each plot (i.e. the maximum value along thc; X-axis) is indicated on the top to left of each plot. As evident, the contour plots differ significantly between the healthy subjects and the 1-enal disease groups.
Fig. 3 Flow sheet for diagnosis and differential diagnosis of renal diseases (example).
Samp., sample; MS-dat., MS-data; Disea., disease; Y, yes; N, no; n.d., no disease;
d.n., diabetic nephropathy, FSGS, FSGS; MGN, MGN; MCD, MCD; IgA, IgA-nephropathy, diff., differential diagnosis The invention is further illustrated by the following examples:
Example 1 Participants:
After local Ethics Committee approval, informed consent was obtained from all participants. We examined a group of 57 healthy individuals with normal renal function in order to establish normal urinary protein patterns with CE-MS. In addition, we studied 44 patients with biopsy-proven minimal-change disease (n: _. 16; MCD), membranous glomerulonephritis (n = 18; MGN), and focal-segmental glomerulosclerosis (n =
10;
FSGS) (Table 1).
CE-MS Analysis:
Spot urine samples were collected from all participants in the morning after voiding the first urine. Samples were prepared as described in detail elsewhere (Wittke S, Fliser D, Haubitz M, et aI: Determination of peptides and proteins in human urine with CE-MS -suitable tool for the establishment of new diagnostic markers. J Chroryccetogr A 1013:173-181, 2003). The CE-MS analysis was established as described previously (Kaiser T, Hermann A, Kielstein JT, et al: Capillary Electrophoresis coupled mass spectrometry to establish polypeptide patterns in dialysis fluids. J Chromatogr A 1013: 157-171, 2003), using a Beckman Coulter PACE system coupled to a Mariner TOF mass spectrometer (ABI). CE capillaries were from Beckman, ID/OD 751360 ~m and 90 cm in length.
The mobile phase used contained 30% methanol and 0.5% formic acid in water. The same liquid was used for the sheath flow, which was applied at 2 ul/min. Sample injection was performed with pressure: 1 psi for 20 sec. Under these conditions about 100 nl of sample could be injected. For sample stacking, the following protocol was applied:
injection of 1M
l0 NH3 for 7 sec., injection of sample, injection of 2M formic acid for 5 sec.
The subsequent CE-MS run was performed at +30 kV with the sequence of the following pressures: 40 min at 0 psi, 2 min at 0.1 psi, 2 min at 0.2 psi, 2 min at 0.3 psi, 2 min at 0.4 psi, 80 min at 0.5 psi. For diagnosis of IgA-nephropathy, the following pressure sequence was used: 40 min at 0.3 psi, 2 min at 0.4 psi, 2 min at 0.6 psi, 2 min at 0.8 psi, 80 min at 1 psi. After each run, the CE capillary was rinsed for 5 min with 0.1 M NaOH, followed by 5 min with water and 5 min with running buffer.
Statistical analysis:
2o For discrimination between healthy subjects and different groups of patients with renal diseases we used the method of Random Forests and the corresponding S-Plus program version 6/2002 Breiman L: Random Forests.
(http://oz.berkeley.edu/users/bre~man/randomforest2001.pdf). In this procedure, a series of PP subsets of fixed size is selected randomly from all candidate PP. For each subset, a classification tree as described in the Classification and Regression Tree (CART) analysis is generated (Steinberg D, Colla P: CART - Classification and Regression trees. San Diego, CA, Salford Systems 1997), resulting in a classification rule. The forest prediction is the unweight plurality of class votes of the series of classification rules. Over-fitting is not generated due to Iarge numbers of subset selections. The estimated generalisation error is unbiased due to the method of "out of bag" (oob) estimation: each tree is grown on a bootstrap sample of cases of the learning sample and the validation is estimated on the basis of those cases not selected in the bootstrap sample.
Further, discrimination between groups was also performed using support vector machines.
This tool has the advantage of discriminating data in high dimensional parameter space. Its fast and stable algorithms showed good performance in the evaluation of clinical markers (Dieterle F, Muller-Hagedorn S, Liebich HM, Gauglitz G: Urinary nucleosides as potential 't tumor markers evaluated by learning vector quantization. Artif Intell.Med 28:265-279, 2003) and different areas of biological analyses like DNA arrays (Brown MP, Grundy WN, Lin D, et al: Knowledge-based analysis of microarray gene expression data by using support vector machines. Proc hTatl Acad Sci USA 97:262-267, 2000).
Normal urinary polypeptide pattern analysed with CE-MS:
A graphical depiction (contour plot) of a typical sample is presented in Fig.
1 (raw data).1n one individual sample, between 900 and 2500 PP with molecular weights from 800 up to l0 30.000 Dalton were detected. Under the conditions used for CE polypeptides with higher molecular weights tend to precipitate. Thus larger proteins in general cannot be detected, although some (e.g. albumin) can be visualised. A list of polypeptides present with high probability that were chosen as internal standards to assure sample comparability is shown in table 23. For analysis of protein-rich samples, such as samples from suspected IgA-nephropathy patients, higher pressure was applied and the polypeptides according to table 24 were preferred as internal standards. Repeated analyses of identical samples did not reveal any significant differences under identical conditions of the CE-MS run for an individual sample.
2o The subsequent electronic data manipulation for one example is summarised in Fig. 1.
Each run results in the crude spectrum depicted in the upper part of Fig. 1 and is composed of single spectra (blow up Fig. I) generated every 3 seconds. CE-MS peaks were identified in the first data analysis run (Fig. lA). Next, the charge of each peak was ascertained utilising both isotopic distribution and conjugated peaks (Fig. 1B). As a result, conjugated peaks were summarised in one single peak and the real mass was calculated, as shown in Fig. 1 C. Initially, the samples were spiked with external standards of known mass. This allowed subsequent definition of internal standards of PP present with high probability in the urine samples. Thus the CE-time could be normalized to the internal standards. By applying this technique on an average urine sample, roughly 1000 PP can be detected and 3o described/identified by the two parameters mass and CE-migration time.
The examination of urine obtained from healthy subjects led to the establishment of peaks defined by actual mass and CE-time of the PP detected, so-called peak lists, and contour plots for each individual. The individual peak lists were deposited in an MS-Access database and the probability of each of the PP to appear in a single sample was calculated.
One-hundred seventy-three PP were present in over 90% of the control samples examined.
In addition, 156 PP were present in more than 75% of the samples, while additional 361 PP

were found in over 50% of samples from the healthy individuals. These 690 PP
were found in more than 50% of all samples obtained from healthy subjects and were used to establish a "normal PP pattern".
Urine from patients with renal diseases analysed with CE-1V~S:
Data from the individual runs of 44 patients were sub-grouped in the three disease groups and analysed. The values from these databases, representing typical PP
patterns, were subsequently compared. Significant homology of the protein patterns present in urine to samples from each patient group was found within the groups. Typical examples of urinary PP patterns from patients with MCD, FSGS, and MGN acre shown in Fig. 2. Each disease presents a typical protein contour plot, revealing more than 500 PP.
Subsequently, the data from the three groups were compared with those obtained in healthy subjects.
Table 16 shows 124 PP found in the urine of more than 95% of healthy subjects and reveals the differences to patients with MCD, FSGS, and MGN.
Statistical analysis for discrimination of healthy individuals and patients with renal disease using CE-MS data was applied. A list of 800 PP, present with more than 50%
probability in either disease group was chosen for Random Forest analysis. The correct classification 2o rate for the discrimination between healthy subjects and renal patients was 96.5 %, as shown in the following list:
Class Healthy Renal Classification subjects error patients (n 57) (n=44) [%

classified 2 3 as 5 healthy 56 .

classified as 42 2 patients .

After cross-validation a sensitivity of 81.3% and a specificity of 94.3% could be obtained.
Discrimination of the disease groups was achieved in the learning sample.
However, most likely due to the small number of FSGS patients, these could not be discriminated from MCD when applying cross-validation. Hence, FSGS and MCD were combined into one group. For the discrimination between healthy subjects, MCD/FSGS and MGN, four PP
were selected by CART from the list to build a classification tree with five terminal nodes (table 15).The correct classification rate in the learning sample is 94.1%.
After cross-validation it reduces to 84.3% (93.8% for healthy controls, 71.4% for MCD/FSGS
and 92.9% for MGN).
Alternatively, statistical analysis was performed using support vector machines on the same data; table 16 shows PP that were employed in this analysis. Using these PP, the correct classification was 98.0% after complete cross-validation. Table 17 depicts PP that were used to discriminate between MCD and MGN. Here the correct classification was 94.1 % after complete cross-validation. Further, it was possible to separate patients with MCD and FSGS and patients with MGN and FSGS with (cross-validated) classification.
rates of 92.3 % and 89.3%, respectively (tables 18 and 19). These results can be valued as a first approach using support vector machines to classify a limited number of patients.
With increasing patients data the classification will further improve and become more stable. The results also indicate that for stable classification the number of applicable;
variables (polypeptides) depends on the number of cases (patients), hence an increase in patients will allow to use even more PP for classification.

SEQUENCE LISTING
(1) GENERAL INFORMATION:
(i) APPLICANT: MISCHAK, Harald KAISER, Thorsten WITTKE, Stephen WALDEN, Michael (ii) TITLE OF INVENTION: METHOD AND MARKERS FOR THE DIAGNOSIS OF
RENAL DISEASES
(iii) NUMBER OF SEQUENCES: 5 (iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: GOUDREAU GAGE DUBUC
(B) STREET: 800 PLACE-VICTORIA, P.O.BOX 242,#3400, Stock Exchange Tower (C) CITY: Montreal (D) STATE: Quebec (E) COUNTRY: Canada (F) ZIP: H4Z lE9 (v) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS
(D) SOFTWARE: PatentIn Release #1.0, Version #1.30 (vi) CURRENT APPLICATION DATA:
(A) APPLICATION NUMBER: CA 2,473,814 (B) FILING DATE: 13-JUL-2004 (C) CLASSIFICATION:
(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: LECLERC, Alain M.
(C) REFERENCE/DOCKET NUMBER: AML/14151.1 (ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: 514-397-7675 (B) TELEFAX: 514-397-4382 (2) INFORMATION FOR SEQ ID N0:1:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 81 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo Sapiens (xi) SEQUENCE DESCRIPTION: SEQ ID N0:1:
Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly Leu His Met (2) INFORMATION FOR SEQ ID N0:2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 89 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo Sapiens (xi)SEQUENCE DESCRIPTION:
SEQ
ID
N0:2:

ThrTyr ValProLys GluPheAsn AlaGluThr PheThrPhe HisAla AspIle CysThrLeu SerGluLys GluArgGln IleLysLys GlnThr AlaLeu ValGluLeu ValLysHis LysProLys AlaThrLys GluGln LeuLys AlaValMet AspAspPhe AlaAlaPhe ValGluLys CysCys LysAla AspAspLys GluThrCys PheAlaGlu GluGlyLys LysLeu ValAla AlaSerGln AlaAlaLeu Gly (2) INFORMATION FOR SEQ ID N0:3:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo sapiens (xi) SEQUENCE DESCRIPTION: SEQ ID N0:3:
Gly Gly Arg Pro Ser Arg Pro Pro Gln (2) INFORMATION FOR SEQ ID N0:4:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo sapiens (xi) SEQUENCE DESCRIPTION: SEQ ID N0:4:
Gly Phe Arg His Arg His Pro Asp Glu Ala Ala (2) INFORMATION FOR SEQ ID N0:5:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 14 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo sapiens (xi) SEQUENCE DESCRIPTION: SEQ ID N0:5:
Gly Leu Ile Thr Leu Ile Gly Ile Asn Pro Ser Leu His Thr Table 1:
molecular migration discrimination weight time [min)factor fre uenc [~a) glomerulo-healthy nephritis 830,5 25,3 0,42 55 12 836,5 35 0,64 80 16 862,4 48,7 0,45 57 12 866,4 37,9 0,62 77 16 870,4 33,9 0,45 52 7 874,5 29,7 0,46 75 29 876,4 48,9 -0,41 57 98 882,6 36,5 -0,4 55 95 903,4 46,8 -0,42 14 55 909,4 40,3 0,67 70 3 925,4 50,7 0,63 77 14 926,5 36,1 -0,44 32 76 943,5 30 0,52 80 28 946,5 _46,8 -0,44 41 84 950,5 36 0,61 66 5 952,5 32 0,52 64 12 956,4 49,5 -0,54 7 60 978,5 35 0,53 55 2 980,6 34,6 -0,45 43 88 982,5 31,9 0,53 64 10 983,5 35,1 0,41 55 __ 988,6 49,9 -0,48 9 57 990,6 32 0,42 61 19 991,4 37,7 0,41 55 14 994,5 33,3 0,51 75 24 995,6 36,4 0,46 68 22 1000,5 34 -0,58 36 95 1006,4 35,7 -0,48 30 78 1008,5 34,4 -0,5 43 93 1010,6 30,6 -0,58 25 83 1013,4 39,3 -0,43 9 52 1015,6 38,2 0,47 52 5 1028,6 37,8 -0,55 43 98 1033,6 39,1 0,62 70 9 1038,6 34,4 0,43 57 14 1046,6 38,6 -0,76 20 97 1047,6 30,4 -0,44 41 84 1073,6 34,7 0,59 75 16 1075,6 29 -0,43 20 64 1102,6 32,9 0,4 52 12 1108,6 29,8 0,47 86 40 1110,4 46,9 -0,5 20 71 1121,6 42,3 -0,46 16 62 1122,5 50,2 -0,41 25 66 - Z
1135,6 42,7 -0,61 5 66 1138,6 39,3 0,55 73 17 1139,6 32,2 0,52 59 7 1141,6 38 -0,6 7 67 1157,6 28,5 0,5 80 29 1159,6 39 -0,65 16 81 1163,7 38,1 0,47 50 3 1171,6 32,8 0,64 66 2 1182,6 47,2 -0,45 20 66 1191,6 50,5 -0,41 50 91 1191,8 18,3 0,56 66 10 1198,8 29,2 0,44 75 31 1203,7 24,7 -0,52 5 57 1209,6 50,5 -0,42 48 90 1211,6 31,3 0,5 66 16 1212,7 30,6 0,57 66 9 1219,6 37,3 0,57 77 21 1220,6 30,2 0,42 75 33 1223,5 51,6 -0,6 30 90 1224,7 33,6 -0,41 59 100 1225,7 41,3 0,45 50 5 1235,6 41,4 -0,41 59 100 1237,7 41,6 -0,49 18 67 1246,7 30,5 -0,47 18 66 1256,6 53,4 0,41 55 14 1264,7 26,7 0,44 52 9 1268,6 53,7 -0,47 5 52 1269,7 39,8 0,45 64 19 1270,5 52,5 -0,51 5 55 1279,7 38,3 0,48 64 16 1280,6 51,9 -0,53 9 62 1286 30,7 0,41 84 43 1292,5 53 -0,59 27 86 1297,6 38,7 0,45 86 41 1302,7 31,8 0,54 86 33 1303,6 40,7 -0,44 11 55 1311,8 31,5 0,58 77 19 1319,9 34,8 0,4 59 19 1324,2 40,5 0,5 59 9 1325,5 35,2 0,54 80 26 1333,8 38,8 0,65 82 17 1335,7 39,2 0,57 80 22 1338,7 29,6 0,46 57 10 1338,7 47,2 0,8 82 2 1350,7 50,3 -0,48 2 50 1353,7 39,3 -0,44 45 90 1354,8 45,6 0,55 93 38 1371,7 39,9 0,6 64 3 1371,8 19,3 0,63 89 26 1389,8 19,5 0,5 84 34 1390,7 41,1 0,45 64 19 1398,9 30,5 0,59 73 14 1401,8 46,2 -0,53 9 62 1405,9 17,3 0,49 59 10 1408,9 26,8 0,42 52 10 1414,6 38,1 0,62 86 _ 1415,7 33,3 0,45 50 5 1419,8 39,7 0,48 77 29 1424,9 35,4 -0,46 25 71 1442,8 33,3 0,63 84 21 1444,6 37,8 0,53 82 29 1448,8 30,3 0,42 75 33 1465,9 28,8 0,59 66 7 1472,1 31,2 0,57 70 14 1474,9 16,9 0,65 77 12 1482 30,4 0,57 84 28 1484 30,4 0,58 89 31 1486,5 30,6 0,45 66 21 1498,7 34,9 0,52 66 14 1499,9 30,6 0,56 91 34 1502,8 28,8 0,44 75 31 1502,9 16,8 0,66 68 2 1508,9 16,8 0,48 57 9 1511,7 38,4 0,55 80 24 1518 26,8 0,45 93 48 1520,7 27,9 0,45 64 19 1527,9 34,7 0,43 73 29 1529,7 54,1 -0,48 36 84 1535 28,3 0,61 73 12 1537,9 31,5 0,43 70 28 1540,7 29,8 0,5 66 16 1542,5 27,2 0,4 52 12 1548,3 31,1 0,46 89 43 1556,8 33,7 0,59 89 29 1567 31,9 0,45 86 41 1567,6 53,9 -0,53 2 55 1568,6 34,3 0,41 70 29 1573,8 4_0,4 0,44 89 45 1574,8 33,9 0,41 61 21 1582,9 27,8 0,51 61 10 1588,4 47,9 -0,61 11 72 1596,9 34 0,64 86 22 1604,3 21,6 0,5 64 14 1604,7 38,1 0,42 73 31 1605,7 __53,3 -0,4 34 74 1611,7 53,2 -0,48 36 84 1612,8 36,8 0,58 91 33 1622 19,2 0,51 91 40 1633,8 24,6 0,42 75 33 1644 18,8 0,46 55 9 1652,3 28,6 0,44 84 40 1669,9 33,4 0,54 75 21 1676 25,3 0,52 _ 12 1681,6 40 0,51 82 31 1686,8 38,2 0,67 91 24 1690,8 25,5 0,44 75 31 1692,5 44,2 -0,41 39 79 1699,1 41,9 0,62 86 24 1711 43,3 -0,45 20 66 1718,5 22,6 0,57 66 9 1726 36,3 0,62 70 9 1729,2 26 0,57 70 14 1732 51,6 -0,41 36 78 1739,8 35,7 0,45 86 41 1746,2 46,2 -0,59 25 84 1747,7 50,8 -0,52 5 57 1752,9 39,9 0,46 68 22 1763 24,4 0,57 80 22 1770,4 45,4 0,4 89 48 1777,6 28,6 0,53 70 17 1793,6 28,3 0,49 55 5 1804,7 34 0,45 100 55 1808,1 45,6 0,49 55 _ 5 1810,1 31,8 0,45 64 19 1811,3 31,3 0,55 93 38 1813,4 54,7 -0,47 7 53 1815,2 27,7 0,5 66 16 1819,9 24,1 0,5 64 14 1820,1 31,8 0,48 91 43 1821,2 18,2 0,52 57 5 1822,9 40,7 -0,6 23 83 1824,3 37 -0,52 27 79 1826,1 21,8 0,45 59 14 1831,9 41,5 0,5 59 9 1847,8 57 -0,66 27 93 1851,2 31,6 0,48 86 38 1853 31,2 0,59 82 22 1853,6 46,7 0,47 50 3 1854,2 28,8 0,45 52 7 1856,8 56,3 -0,51 18 69 1857,1 39 0,46 75 29 1864,6 28,6 0,65 82 17 1867 31,8 0,6 91 31 188_3 29,1 -0,49 32 81 1885,7 57,5 -0,4 55 95 1889,2 30,1 0,41 55 14 1889,8 46,4 -0,58 39 97 1891,6 32,3 0,55 77 22 1894,9 22 0,67 86 19 1896,8 53,3 -0,44 11 55 1898,7 26,5 0,45 59 14 1904 27,5 0,48 50 2 1913,4 30,1 0,44 55 10 1916,8 44,7 -0,52 14 66 1920,7 30,6 0,46 91 45 1933,9 32,8 -0,55 36 91 1934,2 16,1 0,71 73 2 1936,5 46,6 -0,42 25 67 1936,7 32,8 0,5 80 29 1944,2 47 -0,68 18 86 1951,1 53 -0,48 16 64 1966,3 25,1 0,71 82 10 1973,7 57,1 -0,5 9 59 1977,4 42,9 -0,47 41 88 1982,9 32,2 0,58 82 24 1989,3 43,7 0,69 84 16 1990,8 47,3 -0,71 11 83 2011,5 42 0,41 70 29 2022,6 34,6 0,46 68 22 2025 24,2 0,41 50 9 2028,4 29,9 0,55 80 24 2030,4 31,7 -0,49 32 81 2030,8 46,5 -0,61 25 86 2033,5 27,5 0,46 55 2042 26,4 0,47 95 48 2042,5 40,7 0,5 70 21 2045,9 25,3 0,43 84 41 2047 45,4 -0,46 52 98 2050,8 38,2 0,47 82 34 2065,3 20,9 0,49 52 3 2092 26,7 0,52 66 14 2092,5 41,3 0,59 75 16 2099,2 36,9 0,58 84 26 2103,6 26,7 0,46 89 43 2105,4 32,5 0,52 66 14 2109,3 27,9 0,47 68 21 2117,1 57,1 -0,57 20 78 2127,2 39,6 0,46 75 29 2129,5 35,1 -0,58 39 97 2140,1 26,8 0,52 64 12 2144,3 22 0,47 75 28 2146,3 25,8 0,74 77 3 2147,2 38,4 0,43 64 21 2152,7 29,5 0,51 70 19 2157,2 24,4 0,41 50 9 2174,4 24,6 0,46 68 22 2178,5 21,4 0,48 57 9 2182,5 27,6 0,55 80 24 2207,2 41,9 0,41 61 21 2210,7 25,7 0,64 86 22 2217,7 41,9 0,5 84 34 2221,1 40,7 -0,5 14 64 2223,5 22,6 0,6 68 9 2228,1 25,9 0,51 91 40 2233 31,1 -0,4 55 95 2241,1 22,7 0,49 80 31 2290,7 36,2 0,47 52 5 2291,1 21,9 0,45 50 5 2308,9 26,2 0,41 61 21 2312,5 22,9 0,45 57 12 2322,5 47,1 0,47 52 5 2356,3 24 0,41 57 16 2364,4 38,9 0,49 73 24 2370,7 27,3 0,4 52 12 2391,2 24,3 0,58 70 12I

2406,4 31,8 0,43 84 41 2409,1 41,9 0,43 84 41 2421 28,7 0,41 70 29 2423,1 27,4 0,41 68 28 2426,5 38,5 0,58 89 31 2427,4 24 0,53 84 31 2432,2 38,3 0,66 80 14 2464 47,2 -0,55 7 62 2465 22,8 0,7 75 5 2473,4 41,9 0,44 52 _ 9 2490,7 26,7 0,43 70 28 2493,6 24,6 0,63 77 14 2522,9 24,4 0,47 68 21 2529,2 41,4 -0,47 14 60 2535 37,7 0,42 82 40 2540,5 25,5 0,65 75 10 2548,2 35,1 -0,46 36 83 2566,4 22,2 0,5 57 7 256_8,9 26,9 0,41 70 29 2573,7 16,3 0,57 66 9 2584 43,8 -0,56 41 97 2593,4 25 0,41 57 16 __2614,1 22,5 0,42 59 17-2619,7 22,9 0,47 50 3 2621,4 25,8 0,56 68 _ 2644,1 32,5 -0,48 45 93 2660,8 27,1 0,4 59 19 2665,3 39,4 0,46 57 10 2677,6 23,6 0,58 68 10 2698,4 32,1 -0,47 _ 79 2713,2 41,3 -0,51 11 62 2719,9 20,2 0,49 55 5 2752,8 25,3 0,56 82 26 2780,4 28,3 0,52 66 14 2790,3 26,8 0,46 61 16 2793,7 36,3 0,64 80 16 2809,1 37,2 -0,48 30 78 2812,5 32,8 0,46 61 16 2830,9 33;2 0,49 68 19 2937,1 26,6 0,46 55 9 2973,7 34,9 -0,58 30 88 2978 26,3 -0,49 34 83 2990,4 33,6 -0,47 20 67 3007,5 30,5 -0,45 23 67 3017,7 46,8 -0,42 18 60 3057,1 56,4 -0,41 43 84 3058,8 35,5 -0,41 45 86 3121,4 42,5 -0,43 57 100 3137 37 -0,42 41 83 3139,4 43,7 -0,53 25 ___ 3152,6 38,2 -0,45 55 100 3177,4 22,3 -0,45 27 72 3187,7 48,6 -0,4 41 81 3209,2 34,3 -0,47 50 97 3219,5 20,2 0,48 61 14 3255,8 42,9 -0,48 36 84 3262 31,5 -0,52 34 86 ~

3281 36,8 -0,66 32 98 3282 49,4 -0,4 55 95 3290,9 36,9 -0,57 36 93 3295,8 38,4 -0,55 43 98 3303,2 38,6 -0,57 27 84 3308,6 21,3 0,53 57 3 3309,7 43,6 -0,41 32 72 3319,3 46,2 -0,45 50 95 3333,4 23,3 -0,56 32 88 3334,6 41,7 -0,54 32 86 3337,4 36,2 -0,45 43 88 3343,8 43,8 -0,46 45 91 3405,7 37,8 -0,6 39 98 3422,5 38,7 -0,58 32 90 3436 26,4 -0,5 20 71 3479,3 48,5 -0,5 50 100 3503,3 23,2 -0,43 16 59 3530,9 36,8 -0,54 27 81 3583,3 25,2 -0,67 23 90 3589,5 39,1 -0,65 25 90 3617,4 44,8 -0,4 18 59 3631,2 33,1 -0,55 16 71 3634,9 42,6 -0,41 39 79 3682,4 42,8 -0,47 27 74 3686,1 32,6 -0,71 11 83 3697,4 38,8 -0,42 11 53 3701,8 43,4 -0,63 9 72 3707 31,9 -0,69 7 76 371_9,6 44,7 -0,42 41 83 3723_,3 32,5 -0,65 32 97 3735,8 43,9 -0,5 30 79 3760,8 25,9 -0,51 18 69 3802,7 46,2 -0,43 14 57 3816,7 32,2 -0,52 14 66 3852,2 36,9 -0,45 36 81 3871,7 42,9 -0,41 23 64 3946,9 33,1 -0,54 39 93 3969,6 31,3 -0,52 34 86 3987 30,5 -0,42 55 97 4026,2 30,5 -0,42 11 53 4044,7 31,2 -0,57 30 86 4055,2 24,1 0,41 57 16 4154,2 23,7 0,63 77 14 4170,6 46,1 -0,45 7 52 4183,7 26,6 0,42 52 10 4241,2 24,4 0,75 89 14 4283,1 24,3 0,55 64 9 4290,8 41,1 -0,45 43 _ 4654,8 38,8 -0,4 11 52 4713,7 26,9 0,63 68 5 4748,5 25,4 -0,56 39 95 4772,1 28,9 -0,43 9T 52 _ 8 -4801,2 37,5 -0,49 39 88 4827,1 27,3 051 52 .-_ 2 4863,7 39,2 -0,53 18 71 5213,8 36,8 -0,43 7 50 5229,1 39,9 -0,43 9 52 5575,8 35,7 -0,48 14 62 6171,5 39,6 -0,5 43 93 6212,4 30,6 -0,5 9 59 6400,9 23,4 0,51 52 2 7409,9 26,2 0,49 61 12 7556,6 26,2 0,59 75 16 7572,8 25,7 0,42 55 12 8054,8 16,7 0,63 82 19 8341,2 16,6 0,59 66 7 8653,1 17,2 0,4 52 12 8765,9 17,6 0,56 89 33 9060,7 23 0,46 57 10 9076 23 0,58 68 10 9182 17,1 0,55 64 9 9223,1 22,8 0,64 70 7 9335,5 17,5 0,47 50 3 9868,8 29,5 -0,57 20 78 9933,5 18,4 0,47 50 3 10046,3 18,1 0,7 89 19 10390,1 20,2 0, 58 70 12 10518,8 20,9 0,56 75 19 Table 2:
molecular migration discriminationfreouencv f%1 weiaht fDa1time ~min1 factor FSGS healthy 803.4 35 2 0,44 60 16 807.3 35 4 0,41 50 9 809.3 25.2 0,5 50 0 817.2 25.6 0.47 50 3 830.5 25,3 0.68 80 12 836.5 35 0,54 70 16 866.4 37.9 0,64 80 16 870.4 33.9 0.43 50 7 874,4 49.~T 0,57 60 3 907.4 27,5 0.57 60 3 909.4 40,3 0,57 60 3 915,4 35 0.48 50 2 925,4 50.7 0,56 70 14 926.5 36,1 -0.46 30 76 939.6 33,1 0,61 70 9 943.5 30 0.42 70 28 946.5 46,8 -0,54 30 84 950,5 36 0.75 80 5 952.5 32 0.58 70 12 953.6 34,5 -0,52 20 72 956,4 49.5 -0,5 10 60 _ 9 ..
974,5 27,6 0,41 60 19 978,5 35 0,48 50 2 980.6 34,6 -0.58 30 88 981,6 37,4 -0,47 50 97 982.5 31,9 0.7 80 10 988,6 49.9 -0.47 10 57 990.6 32 0,41 60 19 994,5 33.3 0.46 70 24 995.6 36.4 0.48 70 22 1000,5 34 -0.55 40 95 1002.6 38,5 0.53 60 7 1005,5 35 0,54 70 16 1006.4 35.7 -0,58 20 78 1008.5 34.4 -0.63 30 93 1010.6 30.6 -0.53 30 83 1010,6 50.8 -0.64 0 64 1013,4 39,3 -0.52 0 52 1015,6 38,2 0.55 60 5 1021,5 32,1 0,45 50 5 1028.6 37,8 -0.58 40 98 1033.6 39.1 0.71 80 9 1041.5 51,6 -0.4 20 60 1046.6 38.6 -0.77 20 97 1049.5 39,9 0,45 50 5 1055.6 36.4 0.51 60 9 1071,5 38.7 0.48 50 2 1073,6 34.7 0,64 80 16 1075.6 29 -0,44 20 64 1090,5 36,2 0.42 70 _ 28 1106.6 19.6 0,41 50 9 1108,6 29,8 0,4 80 40 1110.4 46,9 -0.41 30 71 1121.6 42.3 -0.62 0 62 1126.5 42,7 0,51 60 9 1135,6 42,7 -0,66 0 66 1138,6 39.3 0.63 80 17 1139,6 32.2 0,53 60 7 1141.6 38 -0.57 10 67 1157,6 28.5 0,51 80 29 1157.6 16.9 0,5 50 0 1159,6 39 -0,61 20 81 1164.6 38.7 0,46 60 14 1171.6 32,8 0,48 50 2 1182,6 47.2 -0,66 0 66 1186.6 32 0,47 80 33 1191,6 50,5 -0,71 20 91 1191.8 18.3 0.5 60 10 1192.6 40,9 0.46 70 24 1203.7 24.7 -0.47 10 57 1209.6 __ -0,5 40 90 50,5 1211.6 31,3 0.64 80 16 1212,7 30.6 0.61 70 9 1219.6 37.3 0.59 80 21 1224,7 33,6 -0.5 50 100 1225,7 41,3 0,55 60 5 1235.6 41,4 -0,4 60 100 1236,7 34,8 0.44 70 26 1237,7 41,6 -0,47 20 67 1246,7 30,5 -0,46 20 66 1258,7 20,9 0.5 60 10 1263,7 38.6 0.65 70 5 1268,6 53,7 -0,52 0 52 1269,7 39.8 0.51 70 19 1270,5 52,5 -0.55 0 55 1270,6 25,7 0,55 60 5 1274,6 38 0.56 70 14 1279.7 38,3 0.44 60 16 1280.6 51,9 -0.52 10 62 1288,6 46.1 -0,44 40 84 1292.5 53 -0,66 20 86 1294,6 54.4 0.56 70 14 1302,7 31,8 0,57 90 33 1303,6 40.7 -0.45 10 _ 55 1304,8 24.6 0,5 50 0 1305,9 33.4 0.6 70 10 1308,6 53.6 -0,54 30 84 1309,8 38,9 0,41 50 9 1310,7 52,5 0,5 50 0 1311,8 31,5 0,51 70 19 1325,5 35,2 0,44 70 26 1333,8 38.8 0.63 80 17 1335,7 39,2 0,68 90 22 1338,7 47,2 0,78 80 2 1338,7 29.6 0,7 80 10 1350,7 50.3 -0,5 0 50 1353.7 39,3 -0,5 40 90 1354.8 45.6 0,52 90 38 1367,7 26,2 0,41 50 9 1371,7 39.9 0,67 70 3 1371,8 19.3 0.64 90 ~ 26 1377.7 25,4 0.67 70 3 1383.7 52.7 -0,53 0 53 1386 24.4 0,41 50 9 1389.8 19,5 0,56 90 34 1390,7 41,1 0.71 90 19 1394.3 48,1 0,48 60 12 1398,9 30.5 0,56 70 14 1401,8 46.2 -0,62 0 62 1403.8 34,4 0.57 60 3 1405.9 17.3 0.6 70 10 1408,9 26,8 0,5 60 10 1411,2 45,4 i 0,41 70 29 1414,6 38.1 ~ 0,76 100 24 1414,7 26,6 0.48 50 2 1419,8 39.7 0.41 70 29 1424,9 35.4 -0.61 10 71 1434,8 41.2 0.48 50 _ 2 1442,8 33,3 0.69 90 _ 21 1444.6 37,8 0.61 90 29 1465.9 28,8 0.53 60 7 1472 ~ 31'2 _0.46 fio- 14 _ -.

1474,9 16,9 0,58 70 12 1482 30.4 0.42 70 28 1484 30,4 0.49 80 31 1487.7 41,4 -0.41 50 91 1490.9 53,4 -0.41 30 71 1493.7 33,7 0.41 70 29 1498,7 34.9 0,46 60 14 1499.9 30.6 0,56 90 34 1501,1 29,5 0.45 50 5 1502.9 16,8 0,68 70 2 1508.9 16,8 0,51 60 9 1511.7 38,4 0,56 80 24 1517.6 54,8 0,48 60 12 1518 26,8 0,52 100 48 1518,9 42,5 0,48 60 12 1520.7 27,9 ~ 0,41 60 19 1527,9 34,7 ; 0.41 70 29 1529.7 54,1 -0.44 40 84 1535 28,3 t 0.68 80 12 1536,6 35 ~ 0.46 60 14 1537.9 31.5 0.52 80 28 1540,7 29,8 0,44 60 16 1547 38.3 0,5 90 40 1548.3 31,1 0.47 90 43 1553.2 54,4 0,48 60 12 1556.8 33.7 0,51 80 29 1567 31.9 0,49 90 41 1567,6 53,9 -0,55 0 55 1588.4 47,9 -0,62 10 72 1589,7 54.3 -0.44 40 84 1591,6 32.6 0,53 60 7 1596.9 34 0,58 80 22 1598,7 28,5 0,48 60 12 1604,3 21,6 0,56 70 14 1604.7 38,1 0,49 80 31 1605.7 53,3 -0,44 30 74 1607.7 41 0.48 60 12 16_11,7 53,2 -0.54 30 84 1612,8 36.8 0,47 80 33 1619,7_ 53.9 -0.52 10 62 1622 19.2 0,6 100 40 1644 18,8 0,41 50 9 1669.9 33,4 0.59 80 21 1671,3_ 25.4 0.42 80 38 1681,6 40 0,59 90 31 1686.8 38.2 0.66 90 24 1692.5 44,2 -0.59 20 79 1695,1 23.6 0,48 60 12 1711 43.3 -0,46 20 66 1713.4 24.6 0,41 60 _ 1718.5 22.6 0,41 50 9 1723,3 26,5 0,43 60 17 1726 36,3 0,61 70 9 1729.1 37,7 0,41 50 9 1729.2 26 0,66 80 14 1732 51,6 -0.48 30 78 1739.8 35,7 0.49 90 41 1746.2 46,2 ~ -0,54 30 84 1747.7 50,8 -0,47 10 57 1751,4 40,8 ! 0,42 80 38 1752.9 39,9 ~ 0,48 70 22 1763 24,4 ~ 0,68 90 22 1770,4 45.4 0,52 100 48 1_772.6 28,5 ~ 0.44 _ 16 _ -- - 60 - ~ ~ -1776.1 43.6 # 40 83 _0 43 1777,6 28.6 ! 0,73 90 17 1783.4 29,2 ' 0.51 70 19 1784,9 31,4 ~ 0.47 50 3 1786,9 35,9 0,53 70 17 1788,6 31 0,49 90 41 1792,4 42,3 0,59 80 21 1794,9 40.4 0.4 80 40 1804.7 34 0.45 100 55 1808.1 45.6 0.55 60 5 1810.1 31.8 0,41 60 19 1811.3 31,3 0,52 90 38 1813,4 54.7 -0.43 10 53 1815.1 39,3 0.41 60 19 1815.2 27,7 0,44 60 16 1820.1 31,8 0,57 100 43 1821.2 18.2 0,45 50 5 1821,5 42,1 0.46 70 24 1822.9 40.7 -0.73 10 83 1824,3 37 -0.59 20 79 1831.7 25.2 0.43 50 7 1831.9 41,5 0,61 70 9 1844,2 34.6 0.62 90 28 1847,8 57 -0.73 20 93 1849,6 37,2 -0.41 40 81 _1851,2 31,6 0,52 90 38 1853 31.2 0.58 80 22 1853.4 18.3 0,5 50 0 1853,6 46.7 0.57 60 3 1854.2 28.8 0,43 50 7 1856,8 56.3 -0,59 10 69 1857.1 39 0,51 80 29 1864.6 28,6 0,43 60 17 1867 31,8 0,49 80 31 __1870,5 16.1 0,45 50 5 1_871,7 43,2 0,65 70 5 1881,4 34,3 0.47 80 33 - l~ -1889,8 _4_6_.4_ -0,67____ 30 97 1891.6 32.3 0.58 80 22 1894,9 22 0,71 90 19 1894,9 56 -0,46 20 66 1898,7 26.5 0,46 60 14 1900,7 30,4 -0.63 20 83 1902,8 33.1 0.53 70 17 1904 27,5 0,48 50 2 1904.3 43,2 0,41 50 9 1916.8 44,7 -0,46 20 66 1920.5 46,1 0.44 60 16 1920,7 30.6 0,45 90 45 1925,3 52,5 0,57 90 33 1928.4 33,2 0,48 70 22 1933,9 32,8 -0,41 50 91 1934,2 16,1 0,78 80 2 19_36.5 46_._6_ -0._47_ 20 67 - - -1936,7 32.8 x.51 80 29 1944.2 47 -0.66 20 86 1950,9 34.5 0.59 90 31 1951,1 53 -0,54 10 64 1966,3 25,1 0,6 70 10 1973.7 57,1 -0.49 10 59 1977,4 42.9 -0.48 40 88 1982.9 32,2 0.46 70 24 1989,3 43,7 0,54 70 16 1990,8 47.3 -0,83 0 83 1999,4 35,6 0.4 80 40 2005,3 39,6 0,49 80 31 2013,8 45,3 -0,47 20 67 2022,6 34,6 0,48 70 ~ 22 2028.4 29.9 0.66 90 24 2030.8 46.5 -0,56 30 86 2033,5 27,5 0,51 60 9 2042 26.4 0,52 100 48 2042,5 40.7 0,49 70 21 2047 45.4 -0,48 50 98 2048,2 33,1 -0,6 40 100 2057,2 36.3 0,43 100 57 2063 24.3 0,6 60 0 2065,3 20,9 0,57 60 3 2077,3 35.8 ~ -0.42 10 52 2092,5 41,3 0.44 60 16 2099.2 36.9 0,54 80 26 2105.4 32,5 0,56 70 14 2114.9 42 0,48 70 22 _2117.1 57.1 -0.68 10 78 2121 26.9 0,61 80 19 2127,2 39,6 0,61 90 29 2140.1 26,8 0.48 60 12 2144,3 22 0.42 70 28 2146,3 25.8 0,57 60 3 2147,2 38,4 0.69 90 21 2163.4 27.6 0,6 70 10 2174.,4 24.6 0,58 80 22 2178,5 21,4 0.41 50 9 2178,7 47.5 -0,4 20 60 2182,5 27.6 0.46 70 24 2200.3 47 0,5 50 0 -2210,7 2~:7 0.58 80 22 2212,9 46,3 -0,44 40 _ 84 2221,1 40,7 -0,44 20 ' 64 2223,5 22,6 0,41 50 9 2228,1 25.9 0.5 90 40 2233 31,1 -0,65 30 95 2257.2 46.6 -0,4 60 100 2258.9 33,6 0,62 100 38 2290.7 36,2 0.45 50 _ 5 2291,1 __21,9_ 0,45 50 5 2322.5 47,1 0.55 60 5 2334,2 41,2 0.45 50 5 2338.2 40,4 0.53 60 7 2367,7 43,2 -0,43 40 83 2375,2 36,5 0,42 80 38 2391.2 24,3 0,48 60 12 2409.1 41,9 0,49 90 41 - .

2423.1 27,4 ~ 0,42 70 28 2426.5 38,5 0,49 80 31 2427.4 24 0,59 90 31 2429,9 39.3 ' -0,46 30 76 2432,2 38.3 0,76 90 14 2435 21.6 0.48 50 2 2438.3 52.6 0,46 60 14 2443.4 31,9 -0,44 40 84 2464 47,2 -0,52 10 62 2465 22.8 0.65 70 5 2473,4 41,9 0,51 60 9 2490.5 43 0,43 60 17 2490.7 26.7 0,42 70 28 2493,6 24.6 0,66 80 14 2529,2 41.4 -0,5 10 60 2536.6 24,8 0,51 60 9 2540.5 25,5 0,5 60 10 2542,6 42,1 0.41 50 9 2568,9 26.9 0,41 70 29 2570.5 57.1 -0,58 20 78 2573.7 16,3 0,51 60 9 2584 43,8 -0,67 30 97 2591,5 37,7 -0.4 10 50 2592,5 56,6 -0.42 20 62 2593,4 25 0,44 60 16 2608,6 37.6 0,43 90 47 2614.1 22.5 0,53 70 17 2619,7 2_2_,9_ 0,47 50 3 2621.4 25.8 0,48 60 12 2627,4 44.8 -0.41 50 91 2646.7 21.9 0,53 60 7 2660,8 27,1 0.51 70 19 _26_77,6 23,6 0,5 60 10 2679,5 35 -0.5 50 100 2687,4 41,9_ -0.4 60 100 2690.3 24.8 0,45 50 5 2713,2 41,3 -0.52 10 62 2720,6 39.5 0.47 50 3 2752.8 25,3 0,44 70 26 2767,4 31,4 -0.55 40 95 2780.4 28.3 0.46 60 14 2793.7 36,3 0,64 80 16 2825,4 36,5_ ~-0,48 50 98 2830.9 33.2 0,51 70 19 __2_841,6_37,1 -0,42 30 72 2854.4 43,8 -0,47 50 97 2883,6 28,9 0,63 80 17 2892,2_ 32,1 0,51 80 29 2898_.5__ 42,3 -0.44 40 84 _2902,9 42,1 0.48 _ 12 2911.7 36.8 -0.54 30 84 2918 42.2 -0.54 20 74 2937.1 26.6 0.51 60 9 2945.1_ 22,6 0.41 50 9 2973.7 34.9 -0.58 30 88 2978 26,3 -0,53 30 83 2986.9 47,3 -0.41 40 81 2990.4 33,6 -0.57 10 67 3012,1 39,4 -0,4 60 100 3017.7 46,8 -0,5 10 60 3022,8 33.8 -0.57 40 97 3038.1 33.7 -0.51 30 81 3047.7 35.9 ~ -0,49 30 79 3057,1 56.4 -0.54 30 84 3058,8 35,5 -0.46 40 86 3080,2 31.7 -0.4 20 60 3098.8 42,6 -0.4 60 100 31_08._8_ 44,7 -0,45 50 95 3121.4 42,5 -0,5 50 100 3137 37 -0.53 30 83 3139.4 43.7 - -0,58 20 78 3152,6 38.2 -0,4 60 100 3158.8 43,3 -0,51 40 91 3166,2 41,2 -0,43 50 93 3177.4 22.3 -0.52 20 72 3187.7 48,6 -0.41 40 81 3209.2 34,3 -0,67 30 97 3255,8 42,9 -0.64 20 84 3262 31,5 -0,46 40 86 3281 36.8 -0.78 20 98 3290,9 36.9 -0,53 40 93 3293.2 54,2 -0,47 50 97 3295,8 38,4 -0,48 50 98 3308.6 21,3 0.57 60 3 3315,1 54,1 -0.61 10 71 3319.3 46,2 -0.45 50 95 3322,8 27.3 -0,48 30 78 3333,4 23,3 -0,68 20 88 3334,6 41,7 -0,56 30 86 3337,4 36,2 -0.58 30 88 3343,8 43,8 -0,61 30 91 3360,1 44,3 -0,4 60 100 3376,2 45,2 -0.47 50 97 3402,4 33,8 -0,48 50 98 3405.7 37,8 -0,58 40 98 3421,8 21,1 0.47 50 3 3422,5 38.7 -0,6 30 90 3436 26.4 -0,61 10 71 3503.3 23.2 -0.49 10 59 3530,9 36,8 -0,51 30 81 3547,3 38.5 -0,4 10 50 3583,3 25.2 -0,9 0 90 3589.5 39,1 -0.8 10 90 3631,2 33.1 -0,51 20 71 3634,9 42,6 -0.49 30 79 3682,4 42.8 -0.44 30 74 3686,1 32.6 -0.73 10 83 3697.4 38.8 -0.43 10 53 3701,8 43,4 -0.62 10 72 3707 31,9 -0,76 0 76 3719.6 44,7 -0.43 40 83 3723,3 32,5 -0.77 20 97 3760.8 25,9 -0.49 20 69 3802.7 46.2 -0.47 10 57 3816.7 32,2 -0,56 10 66 3852.2 36.9 -0,41 40 81 3871,7 42.9 -0.54 10 64 3946,9 33.1 -0,63 30 93 3955,9 23.6 0,41 50 9 3969.6 31,3 -0,46 40 86 3987 30.5 -0,47 50 97 4026,2 30,5 -0,53 0 53 4044.7 31,2 -0,56 30 86 4055.2 24,1 0,54 70 16 4154,2 23,7 0,66 80 14 4170.6 46.1 -0.42 10 52 4241.2 24,4 0,66 80 14 4283,1 24,3 0,41 50 9 4306.5 41.4 -0,4 20 60 4335,8 27.1 0.43 50 7 4527,7 26 0,48 50 2 4594,6 20.6 0,45 50 5 4654,8 38,8 -0,42 10 52 4713.7 26,9 0,65 70 5 4748,5 25.4 -0.45 50 95 4772,1 28,9 -0.42 10 52 5213.8 36.8 -0,4 10 50 5229,1 39.9 -0,52 0 52 5428,4 33.5 -0.44 30 74 5575.8 35.7 -0.52 10 62 5845;8 21,8 0,5 50 0 6171.5 39.6 -0.63 30 93 6212,4 30.6 -0.49 10 59 6238.6 30,9 -0,56 20 76 _75_56.6 26,2 0,44 60 16 7885.4 20 9 0,45 50 5 8054,8 16.7 0,61 80 19 8341,2 16.6 0.53 60 7 8765,9 17,6 0,47 80 33 9076 23 s 0.5 60 10 9223.1 22,8 's 0.53 60 7 9465.1 23,3 E 0,5 50 0 98_68.8 29.5 -0,68 10 78 9933,5 18.4 0.47 50 3 10046.3 18.1 0.61 80 19 10518,8 20.9 0,51 70 19 Table 3:
mo__lecularmi ratio_n discriminationfre uenc fre uenc FSCiS MCD

830,5 25,3 0,49 80 31 865,4 35,5 0,43 80 38 907,4 27,5 0,41 60 19 1005,5 35 0,45 70 25 1008,5 34,4 -0,45 30 75 1015,6 38,2 0,47 60 13 1026,5 33,2 -0,4 _ 50 1041,5 51,6 -0,42 20 63 1055,6 36,4 0,41 60 19 1085,6 50,8 -0,42 20 63 1088,6 37,4 0,49 80 31 1107,5 40,2 -0,45 30 75 1128,5 44,3 0,41 60 19 1138,6 22,9 -0,4 10 50 1160,6 [ 48,8 -0,44 50 94 1191,6 50,5 -0,49 20 69 1199,6 31 -0,63 0 63 1207,7 36,6 0,41 60 _ 1208,6 38,6 0,41 60 19 1211,6 31,3 0,43 80 38 1224,7 33,6 -0,44 50 94 1270,6 25,7 0,41 60 19 1274,6 50,7 -0,44 50 94 1282,7 38,4 0,43 80 38 1294,6 54,4 0,45 70 25 1304,8 __ 24,6 0,44 50 6 1305,9 33,4 0,51 70 19 1308,6 53,6 -0,45 30 75 1377,7 25,4 0,45 _ 70 25 ~

1390,7 41,1 _0,4 90 50 1404,9 29,4 0,43 80 38 1493,7 33,7 0,51 70 19 1518,9 42,5 0,41 60 19 1581 37,8 -0,44 50 94 1594,8 54,8 -0,4 60 100 1607,7 41 0,41 60 19 1650,7 25,4 -0,46 10 56 1695,7 54,7 -0,4 10 50 1766,6 44,9 -0,41 40 81 1826,9 50,8 -0,59 10 69 1880,3 57,4 -0,42 _ 20 63 1887,8 33,8 0,4 __ 90 50 1900,7 30,4 -0,61 20 81 1925,3 52,5 0,59 90 31 1950,9 34,5 0,59 90 31 1992,9 48,5 0,44 50 6 -- -..

2005,3 39 6 0,43 80 38 2011,5 42 -0,64 _ 94 2048,2 33,1 -0,41 40 81 2063 24,3 0,41 60 19 2077,3 35,8 -0,59 10 69 2121 26,9 0,43 80 38 2163,4 27,6 0,51 70 19 2174,4 24,6 0,43 80 38 2258,9 33,6 0,75 100 25 2412,3 42,7 -0,42 20 63 2453,2 49,7 -0,42 20 63 2487,9 38 0,41 60 19 2570,5 57,1 -0,42 20 63 2679,5 35 -0,44 50 94 2690,3 24,8 0,5 50 0 2819,4 32,2 0,44 50 6 2864,7 29,1 -0,49 20 69 2883,6 28,9 0,55 80 25 2889,2 20,2 0,41 60 19 2918 42,2 -0,68 20 88 2986,9 47,3 -0,41 40 81 3209,2 34,3 -0,51 30 81 3255,8 42,9 -0,42 20 63 3315,1 54,1 -0,4 10 50 3402,4 33,8 -0,44 50 94 3583,3 25,2 -0,5 0 50 4335,8 27,1 0,44 _ 6 9182 17,1 -0,42 20 63 Table 4:
molecular migration discrimination fre uenc [%]
weight [Da] time [min] factor FSGS NIGN

819,5 35,7 -0,47 20 67 909,4 40,3 -0,4 _ 60 100 939,6 33,1 0,59 70 11 978,5 23,9 -0,4 10 50 1017,4 36,6 -0,43 40 83 1081,7 29,6 0,49 60 11 1201,5 51,6 0,43 60 17 1282,7 38,4 0,47 80 33 1284,8 55,1 -0,4 10 50 1305,9 33,4 0,42 70 28 1338,7 29,6 0,41 80 39 1341,8 33,1 -0,43 40 83 1359,5 47,4 0,53 70 17 1394,3 48,1 0,43 60 17 1403,8 34,4 0,43 60 17 1423,6 22,3 -0,47 20 67 1490,7 33,7 -0,47 20 67 1493,5 57 -0,46 10 56 1497,9 26,7 -0,48 30 78 1504,4 30,5 -0,42 30 72 1517,6 54,8 ,4 60 17 1526,4 39,4 _ 30 72 _ -0,42 1529,5 32,4 0,43 60 17 1576,4 42,5 0,48 70 22 1591,7 51,2 0,44 100 56 1595,4 31 -0,48 30 78 1692,4 30,4 -0,41 20 61 1734,6 27,2 -0,48 30 78 1768,9 44,7 0,63 80 17 1790,8 38,8 0,4 90 50 1802,5 25,6 -0,42 30 72 1844,2 34,6 0,4 90 50 1883 29,1 0,44 50 6 1885,7__ 57,5 0,42 _ 28 1900,7 3pj4 _.=O'47 _. 70 _ 67.
20_ 1920,5 46,1 0,49 60 11 1925,3 52,5 0,57 90 33 1933,9 32,8 0,44 50 6 1971;5 18,9 -0,47 20 67 1986,6 35,8 -0,42 30 72 2011,5 42 -0,42 30 72 2015,1 49,6 -0,42 30 72 2079,7 21,8 -0,51 10 61 2121 26,9 0,47 80 33 2129,5 35,1 0,43 60 17 2146,3 25,8 -0,4 60 100 2274 37 -0,4 10 50 2292,4 35,3 -0,48 30 78 2299,9 34,3 -0,5 0 50 2312,5 22,9 -0,63 20 83 2338,2 40,4 0,43 60 17 2338,6 26 -0,49 40 89 2356,3 24 -0,43 40 83 2421 28,7 -0,44 50 94 2449,3 28,3 -0,53 30 83 2451,7 35,5 -0,43 40 _ 83 2453,6 32 -0,53 30 83 2469,3 32,5 -0,51 10 61 2471,7 23,8 -0,42 30 72 2525,5 35,6 0,68 90 22 2566,4 22,2 -0,42 30 72 2591,5 37,7 -0,4 10 50 2607 47,6 0,48 70 22 2639,6 45,2 -0,46 10 56 2665,3 39,4 -0,49 40 89 2712,9 22,6 -0,42 30 72 2758,5 40,9 0,42 70 28 2912,9 57,5 -0,4 10 50 3041,2 45 0,41 80 39 3107,2 26,4 -0,4 10 50 3182,9 34,3 0,44 50 6 3313,8 31,6 -0,48 30 78 3479,3 48,5 0,53 70 17 4827,1 27,3 -0,43 40 83 5829,7 20,8 -0,41 20 61 8216,9 16,8 -0,4 10 50 8371,2 15,8 -0,41 20 61 8466,3 18 -0,51 10 61 8518,7 15,7 -0,48 30 78 8578,4 17 -0,47 20 67 9182 17,1 -0,69 20 89 Table 5:
molecular migration discriminationfre uenc weight [Da] time [min]factor FSGS MCD
+ MGN

939,6 33,1 0,49 70 21 1282,7 38,4 - _0,45 $0 35 1305,9 33,4 0,46 70 24 1359,5 47,4 0,44 70 26 1493,7 33,7 0,41 70 29 1650,7 25,4 -0,4 10 50 1734,6 27,2 -0,41 30 71 1900,7 30,4 -0,54 20 74 1925,3 52,5 0,58 90 32 2011,5 42 -0,52 30 82 2121 26,9 0,45 80 35 2258,9 33,6 0,41 100 59 2312,5 22,9 -0,48 20 68 2449,3 28,3 -0,41 30 71 2525,5 35,6 0,49 90 41 2607 47,6 0,41 70 29 2690,3 24,8 0,41 50 9 2918 42,2 -0,51 20 71 9182 17,1 -0,56 20 ~ - - 76~
Table 6:
molecularMigrationdiscriminationfrequenc time [%]

weight [min] factor MCD controt [Da]

836,5 35 0,59 75 16 862,4 48,7 0,44 56 12 866,4 37,9 0,41 56 16 866,5 23,1 0,55 56 2 870,4 33,9 0,43 50 7 - _ _ 876,4 48,9 -0,61 38 98 _ -_ 881,5 25,7 0,46 75 29 882,6 36,5 -0,64 31 95 888,6 29,9 -0,47 6 53 903,4 46,8 -0,49 6 55 914,5 34,3 0,47 50 3 925,4 50,7 0;61 75 14 943,5 30 0,47 75 28 950,5 36 0,51 56 5 956,4 49,5 -0,48 13 60 958,5 32,5 0,46 69 22 974,5 37,9 0,41 50 9 988,5 33,9 0,43 50 7 990,6 32 0;44 63 19 991,4 37,7 0,42 56 14 1000,5 34 -0,51 44 95 1006,4 35,7 -0,4 38 78 1010,6 50,8 -0,45 19 64 1010,6 30,6 -0,52 31 83 1033,6 39,1 0,41 50 9 1034,5 31,4 0,47 50 3 1046,6 38,6 -0;59 38 97 1047,6 30,4 -0,47 38 84 1085,6 50,8 0,49 63 14 1102,6 32,9 0,44 56 12 1104,6 43,3 -0,45 6 52 1108,6 29,8 0,42 81 40 1110,4 46,9 -0,46 25 71 1122,5 50,2 -0,41 25 66 1135,6 42,7 -0,53 13 66 1138,6 39,3 0,7 88 17 1138,6 22,9 0,48 50 2 1139,6 32,2 0,49 56 7 1141,6 38 -0,61 6 67 1159,6 39 -0,56 25 81 1171,6 32,8 0,8 81 2 1182,6 47,2 -0,41 _ 66 1191,8 18,3 0,46 56 10 1199,6 31 0,61 63 2 1203,7 24,7 -0,51 6 57 1219,6 37,3 0,48 69 21 1223,5 51,6 -0,65 25 90 1233,7 49,6 0,45 50 5 1237,7 41,6 -0,42 25 67 1246,7 30,5 -0,41 25 66 1256,6 53,4 0,49 63 14 1264,7 26,7 0,66 75 9 1268,6 53,7 -0,45 6 52 1269,7 39,8 0,44 63 19 1270,5 52,5 -0,49 6 55 1274,6 50,7 0,49 94 45 1280,6 51,9 -0,5 13 62 1292,5 53 -0,49 38 86 1296,6 53,8 0,53 56 3 1302,7 31,8 0,55 88 33 1310,7 36,8 0,41 56 16 1311,8 31,5 0,44 63 19 1324,2 40,5 0,6 69 9 1324,5 54,3 0,45 63 17 1325,5 35,2 0,55 81 26 1333,8 38,8 0,52 69 17 1338,7 47,2 0,86 88 2 1338,7 29,6 0,52 63 10 1350,7 50,3 -0,44 6 50 1354,8 45,6 0,62 100 38 1365 22,3 0,49 63 14 1371,8 19,3 0,49 75 26 1389,8 19,5 0,41 75 34 1401,8 46,2 -0,5 13 62 1414,6 38,1 0,57 81 24 1415,7 33,3 0,51 56 5 1424,9 35,4 -0,52 19 71 1442,8 33,3 0,61 81 21 1444,6 37,8 0,46 75 29 1448,8 30,3 0,42 75 33 1472,1 31,2 0,42 56 14 1474,9 16,9 0,63 75 12 1482 30,4 0,47 75 28 1484 30,4 0,5 81 31 1486,5 30,6 0,61 81 21 1499,9 30,6 0,53 88 34 1502,8 28,8 0, 81 31 1502,9 16,8 _ 56 2 0,55 1508,9 16,8 0,54 63 9 1511,7 38,4 0,7 94 24 1535 28,3 0,57 69 12 1548,3 31,1 U,44 88 43 1556,8 33,7 0,52 81 29 1561,9 28,1 0,46 88 41 1567,6 53,9 -0,55 0 55 1573,8 40,4 0,43 88 45 1574,3 53,4 -0,41 13 53 1588,4 47,9 -0,6 13 72 1591,6 32,6 _ 56 7 0,49 1596,9 34 0,53 75 22 1604,3 21,6 0,55 69 14 1611,7 53,2 -0,41 44 84 1612,8 36,8 0, 88 33 55__ 1622 19,2 _ 81 40 _ ,42 1629,6 49,6 _ 50 3 0,47 -.

1635,2 27,8 0,41 75 34 1644 18,8 0,41 50 9 1658,4 39 0,44 88 43 1669,9 33,4 0,48 69 21 1671,3 42,6 0,42 56 14 1676 25,3 0,44 56 12 1681,6 40 0,.56 88 31 1686,8 38,2 0,63 88 24 1692,4 30,4 0,41 56 16 1699,1 41,9 0,63 88 24 1718,5 22,6 0,48 56 9 1746,2 46,2 -0,53 31 84 1747,7 50,8 -0,51 6 57 1751,4 40,8 0,43 81 38 1752,9 39,9 0,46 69 22 1766,6 44,9 0,52 81 29 1776,1 43,6 -0,45 38 83 1777,6 28,6 0,58 75 17 1804,7 34 0,45 100 55 1811,3 31,3 0,5 88 38 1813,4 54,7 -0,53 0 53 1815,2 27,7 0,41 56 16 1820,1 31,8 0,44 88 43 1821,2 18,2 0,45 50 5 1822,9 40,7 -0,52 31 83 1824,3 37 _p,42 3$ 79.

1831,9 41,5 0,54 63 9 1847,8 57 -0,62 31 93 1851,2 31,6 0,43 81 38 1853 31,2 0,4 63 22 1854,9 53,6 -0,44 6 50 1856,8 56,3 -0,44 25 69 1864,6 28;6 0,64 81 17 1867 31,8 0,56 88 31 1889,8 46,4 -0,53 44 97 1894,9 22 0,56 75 19 1896,8 53,3 -0,43 13 55 1909,7 47,9 0,49 63 14 1913,4 30,1 0,46 56 10 1916,8 44,7 -0,59 6 66 1934,2 16,1 0,48 50 2 1944,2 47 -0,61 25 86 1951,1 53 -0,45 19 64 1955,3 48,4 0,44 63 19 1966,3 25,1 0,65 . 75 10 1973,7 57,1 -0,46 13 59 1982,9 32,2 0,57 81 24 1989,3 43,7 0,66 81 16 1990,8 47,3 -0,7 13 83 2011,5 42 0,64 94 29 2017,6 33,2 0,45 81 36 2030,4 31,7 -0,44 38 81 2030,8 46,5 -0,61 25 86 _2047 45,4 -0,42 56 98 2050,8 38,2 0,47 81 34 2092,5 41,3 0,66 81 16 2098,3 52 0,5 69 19 2099,2 36,9 0,49 75 26 2103,6 26,7 0,44 88 43 2106,1 46,1 0,41 56 16 2117,1 57,1 -0,4 38 78 2129,5 35,1 -0,47 50 97 2130,3 18,4 0,42 56 14 2139,3 36,9 0,41 56 16 2146,3 25,8 0,59 63 3 2151,6 42,6 0,44 56 _12 2157,2 24,4 __0,54 63 _ 9 ~ ~

2182,5 27,6 0,51 75 24 2189,1 40,9 -0,48 19 67 2207,2 41,9 0,48 69 21 2210,7 25,7 0,59 81 22 2217,7 41,9 0,53 88 34 2223,5 22,6 0,54 63 9 2228,1 25,9 0,48 88 40 2238,4 46,3 -0,41 44 84 2281,7 45,6 -0,5 31 81 2426,5 38,5 0,56 88 31 2432,2 38,3 0,55 69 14 2464 47,2 -0,5 13 62 2465 22,8 0,51 56 5 2522,9 24,4 0,42 63 21 2529,2 41,4 -0,42 19 60 2535 37,7 0,42 81 40 2540,5 25,5 0,58 69 10 2548,2 35,1 -0,45 38 83 2566,4 22,2 0,49 56 7 2593,4 25 0'41 56 _ 1.~

2621,4 25,8 0,5 63 12 2644,1 32,5 -0,43 50 93 2698,4 32,1 -0,48 31 79 2713,2 41,3 -0,43 19 62 2752,8 25,3 0,49 75 26 2790,3 26,8 0,41 56 16 27 36,3 0,66 81 16 ,7 _ 37,2 -0,46 31 78 _ 2809,1 __ 30,4 0,43 69 26 2921,4 2933,8 39,4 -0,47 6 53 2973,7 34,9 -0,5 38 88 _3007,5 _ -0,48 19 67 30,5 30 46,8 -0,42 19 60 17,7 _ 43,7 -0,4 38 78 3139,4 3179,2 44,3 0,41 75 34 3262 31,5 -0,49 38 86 3281 36,8 -0,48 50 98 3282 49,4 -0,45 50 95 3290,9 36,9 -0,56 38 93 3295,8 38;4 -0,48 50 98 3333,4 23,3 -0,5 38 88 3334,6 41,7 -0,42 44 86 3343,8 43,8 -0,41 50 91 3433,3 44,5 -0,42 56 98 3530,9 36,8 -0,5 31 81 3589,5 39,1 -0,58 31 90 3631,2 33,1 -0,52 19 71 3686,1 32,6 -0,7 13 83 3697,4 38,8 -0,41 13 53 3701,8 43,4 -0,54 19 72 3707 31,9 -0,63 13 76 3723,3 32,5 -0,47 50 97 3760,8 25,9 -0,5 19 69 3816,7 32,2 -0,47 19 66 4154,2 23,7 0,42 56 14 4170,6 46,1 -0,45 6 52 4241,2 24,4 0,67 81 14 4283,1 24,3 ___0,54 63 9 4707,5 20,5 _0_,42 56 14 _ 4713,7 26,9 0,45 50 5 4748,5 25,4 -0,57 38 95 4772 28,9 -0,4 6 52 ,1 5 _ -- 36-8 _ 6 50 __ _~ 44 _ 5213,8 7409,9 26,2 0,44 56 12 7556,6 26,2 0,53 69 16 8054,8 16,7 0,5 _ 19 8765,9 17,6 0,48 81 33 9076 23 0,58 69 10 9182 17,1 0,54 63 9 9223,1 _22,8 0,56 63 7 9_8_68_,8_29,5 -0 25 78 ,53 10046,3 18,1 _ 81 19 0,62 10390,1 20,2 0,5 63 12 10518,8 20,9 0,62 81 19 Table 7:
molecular migration discriminationfrequency time [%]

weight [min] factor MCD MGN
[Da]

814,5 28,8 -0,46 38 83 819,5 35,7 -0,48 19 67 856,5 28,9 0,42 75 33 863,4 28,8 -0,54 13 67 864,5 37,3 -0,48 19 67 879,6 26,9 0,72 94 22 882,6 36,5 -0,41 31 72 909,4 40,3 -0,56 44 100 928,4 49,4 0,53 81 28 934,5 33,9 -0,41 31 72 935,6 36,6 0,46 63 17 946,5 46,8 0,47 69 22 952,5 32 -0,46 38 83 1005,5 35 -0,42 25 67 1008,5 34,4 0,53 75 22 1015,6 38,2 -0,71 13 83 1017,4 36,6 -0,52 31 83 1022,5 39,1 -0,52 31 83 1028,6 37,8 0,47 69 22 1073,6 34,7 -0,56 44 100 1085,6 50,8 0,51 63 11 1108,5 50,1 0,45 56 11 1113,6 33,7 -0,48 19 67 1138,6 22,9 0,44 50 6 1147,6 49,7 0,46 63 17 1152,5 40,7 -0,65 19 83 1208,6 38,6 -0,42 19 61 1211,6 31,3 -0,46 38 83 1213,6 50 -0,43 13 56 1224,7 33,6 0,6 94 33 1225,7 41,3 -0,42 25 67 1270,6 25,7 -0,48 19 67 1277,6 50 0,46 63 17 1279,7 38,3 -0,63 31 94 1283,9 28,9 -0,48 19 67 1301,7 34 -0,43 13 56 1319,9 34,8 -0,46 38 83 1329,8 37,5 -0,47 25 72 1337,6 52 0,47 69 22 1341,8 33,1 -0,58 25 83 1350,8 26,8 -0,42 19 61 1365 22,3 0,4 63 22 1381,1 32,3 -0,63 31 94 1398,9 30,5 -0,44 50 94 1404,9 29,4 -0,63 38 100 1423,6 22,3 -0,48 19 67 1426,8 38,7 -0,42 25 67 1433 33,7 -0,53 19 72 1465,9 28,8 -0,45 44 89 1482,8 36,3 -0,46 38 83 1487,7 41,4 0,54 88 33 1490,7 33,7 -0,48 19 67 1512,8 35,9 0,41 69 28 1527,9 34,7 -0,44 50 94 1543,8 34,9 -0,52 31 83 1558,1 23,4 -0,42 19 61 1560,5 39,5 -0,46 38 83 1569,8 48,3 0;5 50 0 1574,8 33,9 -0,58 31 89 1593,8 36,7 0,41 69 28 1595,4 31 -0,4 38 78 1602,8 58,1 0,51 63 11 1605,9 23,7 -0,65 13 78 1607,7 41 -0,42 19 61 1612,8 26,3 -0,43 13 56 1623,3 41,4 -0,47 31 78 1671,3 42,6 0,45 56 11 1726 36,3 -0,51 44 94 1729,2 26 -0,45 44 89 1744,1 34,3 -0,63 38 100 1768,9 44,7 0,52 69 17 1774,6 36,5 -0,47 31 78 1786,9 35,9 -0,41 31 72 1799 28,8 -0,47 25 72 1802,5 25,6 -0,53 19 72 1826,9 50,8 0,52 69 17 1839,1 35,5 -0,44 50 94 1857,1 39 -0,44 50 94 1859,4 22,8 -0,42 25 67 1863,8 57,5 0,42 81 39 1876,2 40,1 -0,51 38 89 18_7_8,7 49,9 0,47 75 28 1880,3 57,4 0,51 63 11 1883 29,1 0,44 50 6 1885,7 57,5 0,47 75 28 1887,8 33,8 -0,5 50 100 1898,7 26,5 -0,52 31 83 1924,2 32,9 -0,64 25 89 1933,9 32,8 0,57 63 6 1936,7 32,8 -0,44 56 100 1949,1 38,5 0,43 88 44 1950,9 34,5 -0,58 31 89 1971,5 18,9 -0,48 19 67 1977,4 42,9 0,4 63 22 1988,9 28,8 -0 4 38 78 ~

2005,3 39,6 -0,46 38 83 2011,3_ 29 -0,43 13 56 2033,5 27,5 -0,53 25 _ 2035,6 30,9 -0,54 13 67 2065,3 20,9 -0,47 25 72 2077,3 35,8 0,41 69 28 2109,3 27,9 -0,51 44 94 2140,1 26,8 -0;51 38 89 2152,7 29,5 -0,51 44 94 2160,4 27,9 -0;49 6 56 2163,4 27;6 -0,48 19 67 2167,3 27,8 -0,41 31 72 2174,4 24,6 -0,51 38 89 2178,5 21,4 -0,4 38 78 2189,1 40,9 -0,48 19 67 2258,9 33,6 -0,64 25 89 2274 37 -0,44 6 50 2288,8 41,4 -0,65 13 78 2291,1 21,9 -0,47 25 72 2292,4 35,3 -0,4 38 78 2308,9 26,2 -0,46 38 83 2332,4 35,4 -0,54 13 67 2341,2 26,3 -0,49 6 56 2356,3 24 -0,46 38 83 2367,7 43,2 0,58 75 17 2380 39,6 -0,51 44 94 2391,2 24,3 -0,44 50 94 2423,1 27,4 -0,45 44 89 2434,4 34,7 -0,44 6 50 2446,2 24,7 -0,42 19 61 2451,7 35,5 -0,46 38 83 2453,6 32 -0,52 31 83 2453,8 20,4 -0,49 6 56 2455,6 27,7 -0,41 31 72 2461,1 40,5 -0,47 25 72 2469,3 32,5 -0,42 19 61 2471,7 23,8 -0,41 31 72 2475,5 22,3 -0,42 19 61 2480,2 47,2 0,4 63 22 2483,8 19,6 -0,47 25 72 2493,6 24,6 -0,5 50 100 2500,3 30,4 0,53 75 22 2518,7 38,9 -0,46 38 83 2521,3 48,3 -0,49 13 61 2525,5 35,6 0,4 63 22 2527,3 40,8 -0,53 19 72 2553,7 24,7 -0;42 19 61 2573,7 16,3 -0,45 44 89 2579,5 15,2 -0,48 19 67 2608,6 57,7 0,45 56 11 2614,1 22,5 -0,47 31 78 2619,6 38,3 -0,42 19 61 2642,4 40,9 0,46 63 17 2660,8 27,1 -0,47 31 78 2665,3 39,4 -0,58 31 89 2666 23 -0,43 13 56 2677,6 23,6 -0,51 44 94 2701 34,8 0,4 63 22 2784,3 45,2 -0,59 19 78 -2~-2825,4 36,5 0,49 88 39 2830,9 33,2 -0,57 38 _ ~ 94 2864,7 29,1 0,52 69 17 2889,2 20,2 -0,42 19 61 2902,9 42,1 -0,42 25 67 2912,9 57,5 -0,44 6 50 2921,4 30,4 0,52 69 17 2940,5 40,4 -0,4 38 78 3041,2 45 0,42 81 39 3044,8 48,6 0,4 63 22 3082,3 43,1 0,42 75 33 3169 37,5 0,42 75 33 3205,8 28,3 0,53 75 22 3209,2 34,3 0,48 81 33 3255,8 42,9 0,4 63 22 3256,3 23,1 -0,48 19 67 3303,2 38,6 0,44 50 6 3308,6 21,3 -0,47 31 78 3313,8 31,6 -0,53 25 78 3325,5 43,5 0,44 50 6 3336,8 53,8 0,51 56 6 3405,7 37,8 0,46 63 17 3422,5 38,7 0,45 56 11 3479,3 48,5 0,58 75 17 3578,2 32,5 -0,53 19 72 3881,9 26,2 -0,42 19 61 3969,6 31,3 0,45 56 11 4183,7 26,6 -0,47 31 78 4290,8 41,1 0,4 63 22 _ 4527,7 26 -0,53 19 72 4565,8 __25,1 -0,44 6 50 4719,5 39,3 -0,44 6 50 4827,1 27,3 -0,58 25 83 5112,9 33,1 -0,5 0 50 5829,7 20,8 -0,49 13 61 6106,5 27 -0,56 0 56 7885,4 20,9 -0,49 13 61 8341,2 16,6 -0,57 38 94 8371,2 15,8 -0,49 13 61 8466,3 18 -0,42 19 61 8518,7 15,7 -0,53 25 78 8578,4 17 -0,48 19 67 9335,5 17,5 -0,41 31 72 9465,1 23,3 -0,49 13 61 9944,2 16,7 -0,48 19 67 10949,7 26,3 -0,56 0 56 Table 8:
molecular migration discriminationfre uenc %]
time weight [Da][min] factor MCD FSGS +
MGN

863,4 28,8 -0,45 13 57 879,6 26,9 0,58 94 36 909,4 40,3 -0,42 44 86 928,4 49,4 0,46 81 36 935,6 36,6 0,41 63 21 946,5 46,8 0,44 69 25 952,5 ~ 32 -0 41 38 79 1005,5 35 -0,43 25 68 1008,5 34,4 0,5 75 25 1015,6 38,2 -0,63 13 _ 1022,5 39,1 -0,44 31 75 1028,6 37,8 0,4 69 29 1073,6 34,7 -0,49 44 93 1085,6 50,8 0,48 63 14 1138,6 22,9 0,43 50 7 1147,6 49,7 0,41 63 21 1152,5 40,7 -0,53 19 71 1199,6 31 0,41 63 21 1208,6 38,6 -0,42 19 61 1211,6 31,3 -0,45 38 82 1224,7 33,6 0,54 94 39 1270,6 25,7 -0,46 19 64 1279_,_7 38,3 -0,51 31 82 1341,8 33,1 -0,43 25 68 1381,1 32,3 -0,54 31 86 1404,9 29,4 -0,55 38 93 1433 33,7 -0,46 19 64 1487,7 41,4 0,48 88 39 1543,8 34,9 -0,44 31 75 1560,5 39,5 -0,41 38 79 1569,8 48,3 0,43 50 7 1574,8 33,9 -0,47 31 79 160_2_,8 58,1 0,41 63 21 1605,9 23,7 -0,52 13 64 __1607,7 41 -0,42 19 61 1623,3 41,4 -0,44 31 75 _1726 36,3 -0,42 44 86 1729,2 26 -0,42 44 86 1744,1 34,3 -0,52 38 89 1786,9 35,9 -0,4 31 71 1826,9 50,8 0;54 69 14 1876,2 40,1 -0,41 38 79 1880,3 57,4 0;48 63 14 1887,8 33,8 -0,46 50 96 1898,7 26,5 -0,44 31 75 1924,2 32,9 -0,54 25 79 1933,9 32,8 0,41 63 21 1950,9 34,5 -0,58 31 89 2005,3 39,6 -0,45 38 82 2033,5 27,5 -0,46 25 71 2035,6 30,9 -0,48 13 61 2065,3 20,9 -0,43 25 68 2077,3 35,8 0,47 69 _ 2140,1 26,8 -0,41 38 79 2_15_2,7 29,5 -0,42 44 __ $6 2163,4 27,6 -0,49 19 68 2174,4 24,6 -0,48 38 86 2189,1 40,9 -0,42 19 _ 2258,9 33,6 -0,68 25 93 2288,8 41.,4 -0,55 13 68 2332,4 35,4 -0,45 13 57 2367,7 43,2 0,5 75 25 2493,6 24,6 -0,43 50 93 2500,3 30,4 0,43 75 32 2527,3 40,8 -0,42 19 61 2614,1 ~ 22,5 ~ -0 44 31 __ ~ 75 2660,8 27,1 _ -0,44 31 75 2665,3 39,4 -0,4 _ _ 2784,3 45,2 -0,46 19 __ ~ 64 2825,4 36,5 0,45 88 43 2830,9 33,2 -0,48 38 86 2864,7 29,1 0,51 69 18 2883,6 28,9 -0,43 25 68 2889,2 20,2 -0,42 19 61 2918 42,2 0,45 88 43 2921,4 30,4 0,47 69 21 _3205,8 28,3 0,43 75 32 3209,2 34,3 0,49 81 32 3255,8 42,9 0,41 63 21 3308,6 21,3 -0,4 31 71 3402,4 33,8 0,4 94 54 3578,2 32,5 -0,46 19 64 3583,3 25,2 0,43 50 7 4527,7 26 -0,46 19 64 4827,1 27,3 -0,43 25 68 7885,4 20,9 -0,45 13 57 8341,2 16,6 -0,45 38 82 9465,1 23,3 -0,45 13 57 Table 9:
molecular Migration discriminationfreauencv weight time f%1 fDal fminl factor MGN control 803.4 35.2 0.4 56 16 814.5 28.8 0.59 83 24 815.5 30.9 -0.45 17 62 819,5 35.7 0,63 67 3 830.5 25.3 0.49 61 12 836.5 35 0.73 89 16 844.5 30.9 0.61 61 0 847.5 35.9 0.44 61 17 862.4 48.7 0.55 67 12 863.4 28.8 0.67 67 0 864.5 37.3 0.65 67 2 866.4 37,9 0.79 94 16 870.4 33.9 0.49 56 7 $73.5 38.3 0.45 50 5 874.4 49.7 0.58 61 3 874.5 29.7 0,6 89 29 879:6 26.9 -0.74 22 97 881.5 25.7 0.48 78 29 903.4 46.8 -0.44 11 55 907.4 27.5 0.47 50 3 _ 909.4 40.3 0.97 100 3 925.4 50.7 0.7 83 14 926.5 36.1 -0.48 28 76 928.4 49.4 -0.57 28 84 929.5 39.9 -0.46 33 79 934.5 33.9 0.52 72 21 937.5 41.7 0.48 100 52 943.5 30 0.61 89 28 946,5 46.8 -0.62 22 84 950.5 36 0.61 67 5 952.5 32 0.71 83 12 956.4 49.5 -0,6 0 60 968.6 30.5 0.43 56 12 978.5 35 0.7 72 2 978.5 23.9 0.48 50 2 980,6 34.6 -0,43 44 88 981.6 37.4 -0.41 56 97 982.5 31.9 0.56 67 10 983.5 35.1 0.58 72 14 986.5 30.3 0.54 61 7 987,4 45.1 0.54 56 2 988.5 33.9 0.49 56 7 988.6 4_9,9 -0.57 0 57 990.6 32 0.42 61 19 991.4 37.7 0.47 61 14 994.5 33.3 0.7 94 24 995.6 __36.4 0.61 83 22 998.5 35.8 0.42 56 14 1000.5 34 -0.67 28 95 1005.5 35 0.51 67 16 1006,4 35.7 -0.5 28 78 1008.5 34.4 -0,71 22 93 1010.6 50.8 -0,58 6 64 1010.6 30.6 -0,66 17 83 1013.4 39.3 -0.52 0 52 1015.6 38.2 0.78 83 5 1017.4 36.6 0.63 83 21 1022.5 39.1 0.61 83 22 1028.6 37.8 -0.76 22 98 1033.6 39.1 0.75 83 9 1038.6 34,4 0.58 72 14 1046.6 38.6 -0.91 6 97 1047.6 30.4 -0.46 39 84 1049.5 39.9 0.56 61 5 1051.5 36.2 -0.47 17 64 1055.6 36.4 0.41 50 9 1058.6 21.5 0.56 56 0 1060.6 32 0.55 94 40 1071.5 38.7 0.54 56 2 1073.6 34.7 0.84 100 16 1075.6 29 -0.47 17 64 1081.7 29.6 -0.41 11 52 1090.5 36.2 0.56 83 28 1106,5 37.2 0.44 89 45 1108.6 29.8 0.55 94 40 1109.6 34.9 -0.54 11 66 1110.4 46.9 -0.6 11 71 1114.5 3_7.4 _ -0.48 6 53 1121.6 42.3 -0.51 11 62 1122.5 50.2 -0.43 22 66 1131.7 34.9 0.41 67 26 1132.6 36.7 -0.45 44 90 1134.7 16.9 0.48 50 2 1135.6 42.7 -0.66 0 66 1136.6 31.6 0.43 56 12 1139.6 32.2 0.54 61 7 1141.6 38 -0.62 6 67 1150.6 35.8 0.46 94 48 1152.5 40.7 0.7 83 14 1157.6 28.5 0.6 89 29 1159.6 39 -0.75 6 81 1163.7 38.1 0.58 61 3 1171.6 32.8 0.59 61 2 1181.6 37.8 0.48 89 41 1186.6 32 0.51 83 33 1191.6 50.5 -0.41 50 91 1191.8 18.3 0.67 78 10 1198.8 29.2 0.63 94 31 1199.3 49.9 -0.46 6 52 1203.7 24.7 -0.57 0 57 1211.6 31.3 0.68 83 16 1212.7 30.6_ 0.75 83 9 1219.6 37.3 0.63 83 21 1220.6 30.2 0.51 83 33 1223.5 51.6 -0.67 22 90 1224.7 33.6 -0.67 33 100 1225.7 41.3 0.61 67 5 1226.7 41.6 0.47 50 3 1235.6 41.4 -0.5 50 100 1236.7 34.8 0.41 67 26 1237.7 41.6 -0.56 11 67 1246.7 30.5 -0.54 11 66 1254.8 52.4 -0.44 33 78 1264.6 45.9 0.52 61 9 1268.6 53.7 -0.46 6 52 1269.7 39.8 0.42 61 19 1270.5 52.5 -0.5 6 55 1270.6 25.7 0.61 67 5 1273.8 24.6 0,54 61 7 1274.6 38 0.42 56 14 1277,6 50 -0.45 17 62 1279.7 38.3 0.79 94 16 1280.6 51.9 -0.57 6 62 1283.9 28.9 0.61 67 5 1286 30.7 0.57 100 43 1292.5 53 -0.64 22 86 1297.6 38.7 0.53 94 41 1302,7 31.8 0.51 83 33 1308.6 53.6 -0.4 44 84 1311.8 31.5 0.75 94 19 1319.9 34.8 0.64 83 19 1321.9 41.1 -0.5 50 100 1324.2 40.5 0.52 61 9 1325.5 35.2 0.57 83 26 1331.7 35.4 -0.48 11 59 1333.8 38.8 0.77 94 17 1335.4 53.4 -0.52 0 52 1335,7 39.2 0.72 94 22 1338.7 47.2 0.76 78 2 1341.8 33.1 0.68 83 16 1350.7 50.3 -0.5 0 50 1350,8 26.8 0.46 61 16 1353.7 39.3 -0.51 39 90 1354.8 45,6 0.51 89 38 1355.7 36.3 0.4 56 16 1367.7 26.2 0.41 50 9 1370,8 33 0.41 50 9 1371.7 39.9 0.74 78 3 1371.8 19.3 0,74 100 26 1374.8 42.1 0.43 56 12 1377.7 25,4 0.52 56 3 1378.5 45.4 -0.41 56 97 1381.1 32.3 0.58 94 36 1386 24.4 0.47 56 9 1389.8 19.5 0.54 89 34 1390.7 41.1 0.42 61 19 1395.5 25.4 0.43 50 7 1397,8 36.1 0.45 56 10 1398.9 30.5 0.81 94 14 1401.8 46.2 -0.51 11 62 1404.9 29.4 0.53 100 47 1405.9 17,3 0.62 72 10 1408.9 26.8 0.56 67 10 1414.6 38.1 0.59 83 24 1415.7 33,3 0.45 50 5 1419.8 39.7 0.6 89 2g 1423.6 22.3 0.61 67 5 1424.9 18.5 0.55 67 12 1426,8 38.7 0.58 67 9 1433 33.7 0.46 72 26 1439.6 25,4 0.41 50 9 1439.7 38.1 0.41 8g 4g 1442.8 33.3 0.63 83 21 1444.6 37.8 0.54 83 29 1448.8 30.3 0.45 78 33 1453.1 27.1 0.51 61 10 1462.7 53.6 -0.48 50 98 1465.9 28.8 0.82 89 7 1472.1 31.2 0.75 89 14 1474.9 16.9 0.71 83 12 1482 30.4 0.72 100 28 1482.8 36.3 0.47 83 36 1484 30.4 0.69 100 31 1487.7 41.4 -0.58 33 91 1493.5 57 0.56 56 0 1497.9 26.7 0.57 78 21 1498.7 34.9 0.7 83 14 1499.9 30.6 0.6 94 34 1501.1 29.5 ~ 0.5 56. 5 1502.8 28.8 0.41 72 31 1502.9 16.8 0.76 78 2 1504.4 30.5 0.41 72 31 1508.9 16.8 0.41 50 9 1510.1 39.5 0.48 89 41 1511.7 38.4 0,43 67 24 1518 26.8 0.46 94 48 1520.7 27,9 0,64 83 19 1522.5 26.4 0.42 61 19 1527.9 34.7 0.65 94 29 1529.7 54.1 -0.62 22 84 1535 28.3 0.6 72 12 1537.9 31.5 0,56 83 28 1539.4 28.7 0.49 89 40 1540.7 29.8 0.68 83 16 1542,5 27.2 0,49 61 12 1543.8 34.9 0.54 83 29 1548.3 31.1 0.46 89 43 1552.3 35.5 0.41 100 59 1556.8 33.7 0.71 100 29 1558.1 23.4 0.52 61 9 1567 31.9 0.59 100 41 1567.6 53,9 -0.5 6 55 1568.6 34.3 0.54 83 29 1573.8 40.4 0,5 94 45 1574.3 53.4 -0.42 11 53 1574.8 33.9 0.68 89 21 1576.4 42.5 -0.62 22 84 1578 52.5 -0.48 50 98 1582.9 27.8 0.67 78 10 1588.4 47,9 -0,61 11 72 1589.7 54.3 -0.46 39 84 1595.4 31 0.61 78 17 1596.9 34 0.78 100 22 1604.3 21.6 0.42 56 14 1604.7 38.1 0.41 72 31 1605.7 53.3 -0.46 28 74 1605.9 23.7 0.74 78 3 1607,7 41 0.49 61 12 1611.7 53.2 -0.51 33 84 1612.8 36.8 0.67 100 33 1613.9 36.3 -0.46 39 84 1617.9 44.8 -0.4 44 84 1619.7 53.9 -0.45 _ 62 1622 19.2 0.55 94 40 1629.5 32 0.42 61 19 1633.8 24.6 0.62 94 33 1635.2 27.8 0.43 78 34 1644 18.8 0.52 61 9 1652.3 28.6 0.6 10G 40 1665 27.5 0,45 50 5 1666.3 23.3 0.48 89 41 1669,9 33.4 0.57 78 21 1676 25.3 0.66 78 12 1681.6 40 0.41 72 31 1686.8 38.2 0.7 94 24 1690.8 25.5 0.63 94 31 1692.4 30.4 0.46 61 16 1695.1 23.6 0.43 56 12 1699.1 41.9 0.7 94 24 1702.9 24.5 0.42 56 14 1706.8 21,5 0.51 67 16 1711 43.3 -0.54 11 66 1713.4 24.6 0.42 61 1 g 1718.5 22.6 0.75 83 9 1723.3 26.5 0.49 67 17 1726 36.3 0.86 94 g 1729.2 26 0.75 89 14 1732 51.6 -0.44 33 78 1734.6 27.2 0,47 78 31 1739.8 35.7 0.48 89 41 1744,1 34.3 0.67 100 33 1746,2 46.2 -0.68 17 84 1747.7 50.8 -0.57 0 57 1752.9 39.9 0.44 67 22 1763 24.4 0.72 94 22 1768.9 44.7 -0,63 17 79 1770,4 45,4 0.46 94 48 1772.6 28.5 0.4 56 16 1774.6 36.5 0.61 78 17 1782.1 33 0.43 94 52 1786.9 35.9 0.55 72 17 1788.6 31 0,42 83 41 1791 25 0.58 67 9 1792 25.1 0.4 56 16 1793.6 28.3 0.67 72 5 1802.5 25.6 0.53 72 19 1804.7 34 0.45 100 55 1808.1 45.6 0.56 61 5 1810.1 31.8 0.64 83 19 1811.3 31.3 0.62 100 38 1813.4 54.7 0.42 11 53 1819.9 24.1 0,7 83 14 1820.1 31.8 0.46 89 43 1821.2 18.2 0,61 _ 5 1822.9 40.7 -0.61 22 83 1824.3 37 -0.57 22 79 1826.1 21.8 0.64 78 14 1831.9 41.5 0.41 50 9 1833.5 20.4 0.48 50 2 1837.6 38.2 0.41 72 31 1839.1 35.5 0.58 94 36 1847.8 57 -0.65 28 93 1849.6 37.2 -0.48 33 81 1851.2 31.6 0.51 89 38 1853 31.2 0,78 100 22 1853.6 46.7 0.47 50 3 T

1854.2 28.8 0.54 61 7 1856.8 56.3 -0.52 17 69 1857.1 39 0.65 94 29 1859.4 22.8 0,63 67 3 1860.3 25.9 0.4 56 16 1863.8 57.5 -0.54 39 93 1864.6 28.6 0.77 94 17 1867 31.8 0.69 100 31 1870.4 30.4 0.46 94 48 1870.5 16.1 0.45 50 5 1876.2 40.1 0.65 89 24 1878.7 49.9 -0.52 28 79 1878.9 30.2 0.41 72 31 1880.3 57.4 -0,44 11 55 1883 29.1 -0.75 6 81 1885.7 57.5 -0.67 28 95 1887,8 33.8 0.48 100 52 1889.8 46.4 -0.58 39 97 1891.6 32.3 0.72 94 22 1894.9 22 0.75 94 19 1894.9 56 -0.43 22 66 1896.8 53,3 -0,5 6 55 1898.7 26.5 0.7 83 14 1904 27.5 0.59 61 2 1913.4 30.1 0.51 61 10 1913.9 53.9 -0.4 39 79 1916.8 44.7 -0.49 17 66 1920.7 30.6 0.55 100 _ 1924.2 32.9 0.51 89 38 1931.4 26.6 0.43 56 12 1933.9 32.8 -0.86 6 91 ' 1934.2 16.1 0.87 8g 2 1936.5 46.6 -0.45 22 67 1936.7 32.8 0.71 100 29 1944.1 32.2 0.47 83 36 1944.2 47 -0.75 11 86 1950.9 34.5 8 31 _ 0.58 9~

1951.1 53 -0.47 _ 64 1966.3 25.1 0.84 94 10 1971.3 35,1 0.48 89 41 1971.5 18.9 0.61 67 5 1973.7 57.1 -0.53 6 59 1977 25.5__ 0.46 94 48 1977.4 42.9 -0.66 22 88 1982.9 32.2 0.65 89 24 1986.6 35.8 0.46 72 26 1988.9 28.8 0,61 78 17 1989.3 43.7 0.79 94 16 1990.8 47.3 -0.66 17 83 2005.3 39.6 0.52 83 31 2011,3 29 0.47 56 9 2011.5 42 0.43 72 29 2013.8 45.3 -0.51 17 67 2022.6 34.6 0.55 78 22 2025 24.2 0.58 67 9 2028.4 29.9 0.7 94 24 2030.4 31.7 -0.64 17 81 2030.8 46.5 -0.64 22 86 2032.1 30.6 0.42 56 14 2033.5 27.5 0.69 78 9 2035.6 30.9 0.41 67 26 2042 26,4 0.52 100 48 2042.5 40.7 0.63 83 21 2045.9 25.3 0.53 94 41 2x47 45.4 -0.48 50 98 2050.8 38.2 0.54 89 34 2052.5 38.7 0.41 67 26 2057.2 36.3 0.43 100 57 2065.3 20.9 0,69 72 3 2079.7 21.8 0.54 61 7 2092 26.7 0.75 89 14 2092.5 41,3 0.62 78 16 2093.1 25.3_ 0.47 56 9 2095.3 33.7 0.46 89 43 2099.2 36.9 0.69 94 26 2103.6 26.7 ~ 0.51 94 43 2105.4 32.5 0.64 78 14 2109.3 27.9 0.74 94 21 2116.3 20,3 0.51 67 16 2117.1 57.1 -0.66 11 78 2121,1 43.1 0.4 61 21 2127.2 39.6 0.48 78 29 2129.5 35.1 -0.8 17 97 2140.1 26,8 0,77 89 12 2144.3 22 0.67 94 28 2146.3 25.8 0.97 100 3 2152.7 29.5 0.75 94 19 L.. I I

2163.4 27.6 0.56 67 10 2167.3 27.8 0,45 72 28 2172.5 36.7 0.46 94 48 2174:4 24.6 0.66 89 22 2178.5 21.4 0.69 78 9 2182.5 27.6 0.65 . 89 24 2197.9 29 0.48 67 19 2200.2 33,6 0.47 78 31 2205.6 23 0.42 56 14 2207.2 41.9 0.46 67 21 2210.7 25.7 0.72 94 22 2212.9 46.3 -0.46 39 84 2217.7 41.9 0.6 94 34 2221.1 40.7 -0.64 0 64 2223.5 22.6 0.75 83 9 2228.1 25.9 0.55 94 40 2230.1 22.8 0.52 56 3 2241 41.1 0.47 78 31 2241.1 22.7 0.63 94 31 2246.6 39,1 0,41 94 53 2253.1 22.4 0.54 56 2 2258.8 33.6 0.51 89 38 2264.4 34.8 -0.44 17 60 2266 18.5 0,5 50 0 2273.5 22.4 0.42 56 14 2279.1 47,2 -0.5 44 95 2279.5 34.8 0.46 94 48 2288.8 41.4 0.45 78 33 2288.9 27 0.48 67 19 2290.7 36.2 0.61 67 5 2291.1 21.9 0.67 72 5 2302.9 36.7 0.52 100 48 2308.9 26.2 0.63 83 21 2312.5 22.9 0.71 83 12 2322.5 47.1 0.61 67 5 2325.5 19.5 0.5 50 0 2334.2 41.2 0.45 50 5 2352.4 24.7 0.42 61 19 2356.3 24 0,68 83 16 2364.4 38.9 0,65 89 24 2367.7 43.2 -0.66 17 83 2370.7 27.3 0.49 61 12 2380 39.6 0.62 94 33 2383.9 21,1 0.52 56 3 2389.2 34.4 0.41 8g 4g 2391.2 24.3 0.82 94 12 2396.5 34.6 0.49 61 12 2406.4 31.8 0.59 100 41 2409.1 41.9 0.48 89 41 2414,5 40.8 0.4 61 21 2421 28.7 0.65 94 29 2426.5 38,5 0.63 9 31 2427.4 24 0.63 _ 31 2429.9 39.3 -0.48 28 76 2432.2 38.3 0.7 83 14 2435 21.6 0.54 _ 2 2443.4 31.9 -0.46 39 84 2446.2 24.7 0,44 61 17 2449.3 28.3 0.45 83 38 2451.7 35.5 0.44 83 40 2453.6 32 0.7 83 14 2453.8 20.4 0.56 56 0 2455.6 27.7 0.5 72 22 2461.1 40.5 0.58 _ 14 2464 47.2 -0.62 0 62 2465 22.8 0.89 94 5 2469,3 32.5 0.49 61 12 2471.7 23.8 0.53 72 19 2473.4 41,9 0.52 61 9 2475.5 22.3 0.49 61 12 2480.2 47.2 -0.5 22 72 2483.8 19.6 0.55 72 17 2485.9 47.5 0.41 72 31 2490.7 26.7 0.56 83 28 2493.4 46 -0.48 33 81 2493,6 24.6 0.86 100 14 2500.3 30.4 -0.57 22 79 2502.9 33 0.46 61 16 2507.3 17.2 0.48 50 2 2518.7 38.9 0.59 83 24 2521.3 48.3 0.56 61 5 2522.9 24.4 0.63 83 21 2525.5 35.6 -0.64 22 86 2527.3 40.8 0.6 72 12 2529.2 41.4 -0.49 11 60 2535 37,7 0.55 94 40 2536.6 24.8 0.47 56 9 2540.5 25.5 0.79 89 10 2548.2 35.1 -0.55 28 83 2553.7 24.7 0.44 61 17 2561.3 21.6 0.48 50 2 2566.4 22.2 0.65 72 7 2568.9 26.9 0,48 78 29 2570.5 57.1 -0:44 33 78 2573,7 16.3 0.8 gg g 2576,2 25.4 0.46 67 21 2579.5 15.2 0.63 67 3 2584 43.8 -0.69 28 97 2592.5 56.6 -0.45 17 62 2593.4 25 0.4 56 16 2601.6 23.2 0.45 56 10 2607 47.6 -0.52 22 74 2614.1 22.5 0.61 78 17 2619.6 38.3 0.4 61 21 2619.7 22.9 0,63 67 3 2621.4 25.8 0.66 78 12 2627.4 44,8 -0.41 50 91 2630.6 41.7 0.53 72 19 2639.6 45.2 0.5 56 5 2642.4 40.9 -0.61 17 78 2644.1 32.5 -0.6 33 93 2646.7 21.9 0.43 50 7 2654.3 37.2 -0,54 11 66 2658.5 24.7 -0.42 44 86 2660.8 27.1 0.59 78 19 2665.3 39.4 0.79 89 10 2666 23 0.45 56 10 2677.6 23.6 0.84 94 10 2687,9 28.2 0.5 56 5 2697.3 42.4 -0.48 6 53 2698.4 32.1 -0.52 28 79 2706.7 18.5 0,48 50 2 2707.2 34.1 0.45 72 28 2712.9 22.6 0.52 72 21 2713.2 41.3 -0.57 6 62 2719.9 20,2 0.67 72 5 2733.4 34.6 -0.42 44 86 2752.8 25,3 0.69 94 26 2758.5 40.9 -0.43 _ 71 2775.5 26.3 0.43 50 7 2780.4 28.3 0,7 83 14 2784.3 45.2 0.61 78 17 2790.3 26.8 0.62 78 16 2793.7 36.3 0.62 78 16 2809.1 37.2 -0.61 17 78 2812.5 32.8 0.62 78 16 2823.3 39,9 -0.43 44 88 2825.4 36.5 -0.59 39 98 2830,9 33.2 0.75 94 19 2834.1 38.2 -0.45 28 72 2841.6 37.1 -0.45 28 72 2848,8 36.3 -0.5 44 95 2854.4 43.8 -0.41 56 97 2875.1 59.1 0.5 50 0 2883,6 28.9 0.44 61 17 2898.5 42.3 -0.4 44 84 2902.9 42.1 0.55 67 12 2908.2 49.2 -0.42 _ 64 2912.9 57.5 0.5 50 0 2937.1 26.6 0.52 61 9 2945.1 22.6 0.52 61 9 2972.2 25.6 0.48 67 19 2973.7 34.9 -0.66 22 88 - 4~ -2978.3 41.7 -0.52 28 79 2990.4 33_.6 -0.51 1 T 67 3007.5 30.5 -0.45 22 67 3041.2 45 -0.61 39~ 100 3044.8 48.6 -0.52 22 74 3057.1 56.4 -0.51 33 84 3058.8 35.5 -0.42 44 86 3061.9 30,4 0.54 89 34 3077 28.4 -0.55 28 83 3082:3 43.1 -0.46 33 79 3098.8 42.6 -0.44 56 100 3114.9 44.5 -0.53 33 86 3121.4 42.5 -0.56 44 100 3133.8 43.9 -0.45 17 62 3139.4 43,7 -0.61 17 78 3149.7 41.6 -0.48 50 98 3152.6 38.2 -0.61 39 100 3169 37,5 -0.41 33 74 3177.4 22.3 -0.5 22 72 3187.7 48.6 -0.53 28 81 3190.9 28.8 -0.42 22 64 3193.1 35.5 -0.46 6 52 3205.8 28.3 -0,64 22 86 3209.2 34.3 -0.63 33 97 3219.5 20.2 0.7 83 14 3232.5 35.7 -0.46 11 57 3255.8 42.9 -0.62 22 84 3256.3 23.1 0.65 67 2 3258.6 36.3 -0.52 17 69 3260.9 57.3 -0.48 6 53 3262 31.5 -0.58 28 86 3281 36,8 -0,76 22 98 3290.9 36.9 -0.6 33 93 3293.2 54.2 -0,47 50 97 3295.8 38.4 -0.65 33 98 3300.3 44.5 0,41 50 9 3303.2 38.6 -0.79 6 84 3308.6 21.3 0.74 78 3 3309.7 43.6 -0.56 17 72 3319.3 46.2 -0.56 39 95 3320 26.7 0.42 56 ' 14 3333.4 23.3 -0.55 33 88 3334.6 41.7 -0.64 22 86 3336.8 53.8 -0.58 6 64 3337.4 36.2 -0.49 39 88 3343.8 43.8 -0.41 50 91 3372.2 32.5 0.51 83 33 3381.9 43.9 -0.42 11 53 3398.9 44.5 -0.41 50 91 3402.4 33.8 -0.43 56 98 3405.7 37.8 -0.82 17 98 ~

3433.3 44.5 56 gg -0.43 3436 26.4 17 71 -0.54 3442.8 42.5 -0.44 56 100 3451,5 32,6 -0.43 22 66 3479.3 48.5 -0.83 _ 100 3503.3 23.2 -0.48 11 59 3530.9 36.8 -0,59 22 81 3552 38.8 -0.48 6 53 3578.2 32.5 0.58 72 14 3583.3 25.2 -0.79 11 90 3589.5 39.1 -0,62 28 90 3617.4 44.8 -0,53 6 59 3631.2 33.1 -0.6 11 71 3634.9 42.6 -0,52 28 79 3669.7 36.7 -0.47 17 64 3682.4 42.8 -0.57 17 74 3686.1 32.6 -0.72 11 83 3697.4 38.8 -0.42 11 53 3701.8 43.4 -0.72 0 72 3707 31.9 -0.7 6 76 3719.6 44.7 -0.55 28 83 3723.3 32.5 -0.74 22 g7 3735.8 43.9 -0.68 11 79 3739.7 47.7 -0.44 33 78 3760.8 25.9 -0.52 17 69 3802.7 46.2 -0.51 6 57 3816.7 32.2 -0.54 11 66 3852.2 36.9 -0.59 22 81 3871,7 42,9 -0.42 22 64 3881,9 26.2 0.51 61 10 3946.9 33.1 -0.65 28 93 3955.9 23.6 0.41 50 9 3969.6 31.3 -0.75 11 86 3987 30,5 -0.52 44 97 4006.7 45.9 -0.43 22 66 4026.2 30.5 -0.48 6 53 4044.7 31.2 -0.75 11 86 4055.2 24.1 0.46 61 16 4102.1 41.9 -0,5 0 50 4154.2 23.7 0.81 94 14 4170.6 46.1 -0.46 6 52 4183.7 26.6 0.67 78 10 4241.2 24.4 0.86 100 14 4283.1 24.3 0.64 72 4290.8 41.1 -0.66 22 88 4364.4 23,9 -0.42 11 53 4369.9 27.1 0.53 94 41 4527.7 26 0.7 72 2 4565.8 25.1 0.41 50 9 4626,4 27.2 0.61 67 5 4654.8 38.8 -0.41 11 52 -4~-4719.5 39.3 0.5 50' 0 4748.5 25.4 -0.61 33 95 4772.1 28.9 -0.41 11 52 4801.2 37.5 -0.71 17 88 4827.1 27.3 0.82 83 2 4863.7 39.2 -0.65 6 71 5112.9 33.1 0.5 50 0 5213.8 36.8 -0.44 6 50 5229.1 39.9 -0,41 11 52 5575.8 35.7 -0.57 6 62 5829.7 20.8 0.59 61 2 5845.8 21.8 0.5 50 0 6106.5 27 0,56 __ 0 _ 6171.5 39.6 -0.54 39 93 6212.4 30.6 _ -0.59 0 59 6238.6 30.9 -0.43 33 76 6400.9 23.4 0.7 72 2 7190.3 26.5 0,43 50 7 7284.9 40.7 0.5 50 0 7409.9 26.2 0.6 72 12 7556.6 26.2 0.73 89 16 7572.8 25.7 0.55 67 12 7885.4 20,g 0.56 61 5 8054.8 16.7 0.75 94 19 8216.9 16.8 0.45 50 5 8341.2 16.6 0.88 94 7 8371.2 15.8 0.61 61 0 8466.3 18 0.56 61 5 8518.7 15.7 0.76 78 2 8578.4 17 0.61 67 5 8653,1 17.2 0.55 67 12 8765.9 17.6 0.67 100 33 8803.1 16.2 0.47 _ 3 8928.6 17 0.49 56 7 9060.7 23 0.62 72 10 9076 23 0.62 72 10 9182 17.1 0.8 8g 9 9208 22.9 0.61 67 5 9223.1 22.8 0.76 83 7 9335.5 17.5 0.69 72 3 9465.1 23.3 0,61 61 0 9480.1 23.6 0.56 56 0 9621.9 19.2 0.58 67 9 9868.8 29.5 -0.55 22 78 9933.5 18,4 0.52 56 3 9944.2 16.7 0.63 67 3 10046.3 18.1 0.81 100 19 10390.1 20.2 0.77 89 12 10518.8 20.9 0.53 72 19 10949.7 26.3 0.5 56 5 Table 10:
molecular migrationdiscriminationfrequency weight time [min]factor [%]
[Da]

MGN FSGS +
MCD

814,5 28,8 0,41 83 42 819,5 35,7 0,47 67 19 863,4 28,8 0,44 67 23 864,5 37,3 0,44 67 23 879,6 26,9 -0,59 22 81 909,4 40,3 0,5 100 50 _928,4 49,4 -0,41 28 69 1015,6 38,2 0,53 83 31 1017,4 36,6 0,49 83 35 1022,5 39,1 0,41 83 42 1073,6 34,7 0,42 100 58 1152,5 40,7 0,53 83 31 1224,7 33,6 -0,44 33 77 1279,7 38,3 0,52 94 42 1283,9 28,9 0,44 67 23 1301,7 34 0,4 56 15 1319,9 34,8 0,41 83 42 1329,8 37,5 0,41 72 31 1341,8 33,1 0,53 83 31 1381,1 32,3 0,48 94 46 1404,9 29,4 0,46 100 64 1423,6 22,3 0,47 67 19 1433 33,7 0,41 72 31 1490,7 33,7 0,47 67 19 1543,8 34,9 0,41 83 42 1574,8 33,9 0,47 89 42 1595,4 31 0,43 78 35 1602,8 58,1 -0,43 11 54 1605,9 23,7 0,55 78 23 1612,8 26,3 0,4 56 15 1726 36,3 ~ 0,41 94 54 1744,1 34,3 0,5 100 50 1768,9 44,7 -0,56 17 73 1774,6 36,5 0,43 78 35 1799 28,8 0,41 72 31 1802,5 25,6 0,49 72 23 1839,1 35,5 0;41 94 54 1876,2 40,1 0,43 89 46 1883 29,1 -0,44 6 50 1885,7 57,5 -0,45 28 73 1898,7 26,5 0,41 83 42 1924,2 32,9 0,5 89 38 1933,9 32,8 -0,52 6 58 1971,5 18,9 0,47 _ 19 2011,3 29 0,4 56 15 2079,7 21,8 0,42 61 19 2109,3 27,9 0,44 94 50 2140,1 26,8 0,43 89 46 2152,7 29,5 0,41 94 54 2160,4 27,9 0,4 56 15 2274 37 0,42 50 8 _ 2288,8 41,4 _ 0,51 ( 78 _ ~ 27 2292,4 35, 0,43 78 ~ 35 2312,5 22,9 0,45 83 38 2332,4 35,4 0,44 67 23 2338,6 26 0,43 89 46 2341,2 26,3 0,44 56 12 2356,3 24 0,45 83 38 2367,7 43,2 -0,45 17 62 2380 39,6 0,44 94 50 2391,2 24,3 0,41 94 54 2421 28,7 0,41 94 54 2451,7 35,5 0,45 83 38 2453,6 32 0,53 83 31 2453,8 20,4 0,44 56 12 2461,1 40,5 0,41 72 31 2469,3 32,5 0,46 61 15 2471,7 23,8 0,41 72 31 2500,3 30,4 -0,43 22 65 2521,3 48,3 0,42 61 19 2525,5 35,6 -0,51 22 73 2527,3 40,8 0,45 72 27 2639,6 45,2 0,4 56 15 2642,4 40,9__ -0,41 17 58 2665,3 39,4 0,54 89 35 2677,6 23,6 0,44 94 50 _2784,3 45,2 0,51 78 27 2830,9 33,2 0,44 94 50 2912,9 57,5 0,42 50 8 3041,2 45 -0,42 39 81 _3_205,8 28,3 -0,43 22 65 3256;3 23,1 0,44 67 23 3313,8 31,6 0,51 78 27 3336,8 53,8 -0,44 6 50 3479,3 48,5 -0,56 17 73 3578,2 32,5 0,41 72 31 418_3,7 26,6 0,43 78 35 4527,7___26 0,41 72 31 4827,1 2_7,3 0,53 83 31 5112,9 33,1 0,42 50 8 5829,7 20,8 0,46 61 15 6106,5 27 0,48 56 8 8341,2 16,6 0,48 94 46 8371,2 15,8 0,46 61 15 8466,3 18 0,46 61 15 8518,7 15,7 0,51 78 27 8578,4 17 0,47 67 19 9182 17,1 0,43 89 46 9944,2 16,7 0;44 67 23 10949,7 26,3 0,48 56 8 Table 11:
molecularmigrationdiscriminationfrequency [%J

weight time [min]factor IgA control [Da] +
MGN

800,5 22,5 -0,41 14 55 866,5 22 0,52 52 0 874,7 19,2 0,45 52 7 879,5 15,6 -0,84 9 93 937,5 23 0,43 57 14 981,6 21,3 -0,42 34 76 995,5 21,4 0,5 54 3 1010,6 16,3 -0,57 5 62 1028,6 21,2 -0,56 13 69 1046,5 21,5 -0,74 9 83 1060,7 17,4 0,47 61 14 1134,6 20,4 -0,59 41 100 1169,5 45,7 -0,52 4 55 1194,7 22,9 -0,68 32 100 1219,7 23,7 0,43 61 17 1224,7 18,1 -0,58 11 69 1235,3 23,2 -0,59 27 86 1250,6 23 -0,52 48 100 1265,6 23 -0,77 23 100 1285,8 18 0,54 57 3 1297,6 22,1 0,61 75 14 1321,7 23,6 -0,46 20 66 1333,7 22,8 0,54 54 0 1335,5 21,1 0,45 63 17 1368,8 17 0,65 75 10 1386,9 17,2 0,75 79 3 1404,8 16 0,61 75 14 1424,4 32,1 -0,57 43 100 1438,5 23,6 -0,43 54 97 1448,6 17,5 0,57 64 7 1460,9 19,5 0,54 54 0 1482 17,7 0,65 71 7 1493,8 20 0,48 52 3 1499,9 17,6 0,77 88 10 1539,7 34,1 -0,72 25 97 1567 19,2 0,59 63 3 1579,5 22,9 -0,56 30 86 1585 18,1 0,77 91 14 1621,8 13,4 0,47 75 28 1644,4 20,8 0,63 63 0 1651,9 17,2 0,64 68 3 1698,1 18,4 0,72 96 24 1760 17,7 0,5 57 7 1805,1 19,8 0,5 50 0 1811,2 17,9 0,83 96 14 _1819,7 20,4 0,52 59 7 1829,1 18 0;5 98 48 1851,1 17,8 0,77 84 7 1863,8 37 -0,52 38 90 1867,2 18,6 0,82 86 3 1872,9 18,6 ~ 0,65 71 7 1878,5 17,3 0,52 59 7 1_880,1 37,5 -0,48 7 55 1895,1 16,2 0,63 77 14 1924,5 20,4 0,52 52 0 1943 19,5 0,79 86 7 1955 19,9 0,41 52 10 1977 12,7 -0,57 5 62 _2039,1 18,6 -0,49 27 76 2_042,1 17,7 0,68 75 7 2048 19,9 -0,54 46 100 2057,3 19,1 0,71 71 0 2133,3 21,5 0,5 64 14 2147 19,5 0,54 68 14 2174,9 27,8 -0,81 9 90 2233,1 18,1 -0,48 11 59 2246,2 22,1 0,68 68 0 2249,1 18,7 -0,42 23 66 2258,6 18,9 0,5 50 0 2279,5 22,5 0,5 54 3 2377,4 18,4 -0,67 13 79 2389,2 18,6 0,59 66 7 2405,6 17,8 0;59 59 0 2427,1 16,4 0,84 95 10 2502,2 19,2 0,5 61 10 2518,7 18,8 0,61 64 3 2540,4 16 0,68 75 7 2562,9 19,1 -0,52 38 90 2566,7 13,9 0,66 70 3 2608,3 21,8 0,54 75 21 2621,5 16,5 0,68 71 3 2649,6 28,9 -0,5 13 62 2695,4 19,7 -0,54 43 97 2742,3 23,7 -0,61 36 97 2752,4 15,5 0,83 93 10 2755,3 23,6 0,68 71 3 2790,6 16,4 0,64 64 0 2799,7 20,4 -0,45 48 93 2825 20,8 -0,63 38 100 2838,7 20,3 -0,57 36 93 2914,8 17 0,43 50 7 2936,8 16 0,7 70 0 3011,5 24,5 -0,68 32 100 3013,3 16,8 -0,42 20 62 3040,9 25,5 -0,72 25 97 3098,3 24,8 -0,51 11 62 3205,9 15,7 -0;53 9 62 3209,4 19 -0,67 16 83 3265,5 24 -0,66 23 90 3281,1 27,3 -0,56 38 93 3287,4 25,2 -0,54 39 93 3303,5 28,7 -0,49 23 72 3333,2 14,1 -0,64 5 69 3359,6 26,2 -0,72 4 76 3375,6 25,3 -0,5 9 59 3385,7 21,2 -0,61 32 93 3402,3 17,8 -0,56 13 69 3405,3 21,6 -0,75 18 93 3416,7 26,4 -0,46 9 55 3432,5 25,6 -0,69 7 76 3441,6 25,4 -0,45 55 100 3457,8 25,4 -0,45 55 100 3_502,8 14,8 -0,48 7 55 3582,9 14,2 -0,72 7 79 3969,1 18,1 -0,43 13 55 3987,1 17,3 -0,63 27 90 4044,5 18 -0,44 14 59 4054,8 15,5 0,45 59 14 4098,2 20,5 -0;56 23 79 4153,7 14,7 0,58 71 14 4240,6 14,8 0,63 84 21 4290,3 23,4 -0,65 7 72 4306,5 23,5 -0,57 2 59 4369,2 15,5 0,44 75 31 4626 15,7 0,52 55 3 4712,9 15,8 0,72 79 _ 4748 14,7 -0,67 20 86 6171,4 23 -0,7 16 86 6186,7 23,3 -0,67 20 86 8764,7 12,8 0,46 88 41 9868,4 17,2 -0,63 9 72 1_0044,3 13,1 0,65 89 24 10516,9 13,9 _ _ 0,45 52 12719 22,6 -0,44 25 69 Table 12:
molecularmigration discriminationfrequency weight time factor [%) [Da) [min) IgA
control 800,5 22,5 -0,44 12 55 852,6 19,7 0,51 51 0 862,4 27,2 0,56 56 0 866,5 22 0,58 58 0 879,5 15,6 -0,91 2 93 937,5 23 0,49 63 14 981,6 21,3 -0,48 28 76 995,5 21,4 0,55 58 3 1008,5 20 -0,44 12 55 1010,6 16,3 -0,6 2 62 1028,6 21,2 -0,57 12 69 1033,7 21,6 0,53 53 0 1046,5 21,5 -0,8 2 83 1134,6 20,4 -0,63 37 100 1144,7 25,8 0,48 51 3 1169,5 45,7 -0,51 5 55 1181,6 23,7 0,48 65 17 1194,7 22,9 -0,65 35 100 1219,7 23,7 0,55 72 17 1224_,7 18,1 -0,64 5 69 1235,3 23,2 -0,61 26 86 1250,6_ 23 -0,49 51 100 1265,6_ 23 -0,79 21 100 1297,6 22,1 0,63 77 14 1321,7 23,6 -0,52 14 66 1333,7 22,8 0,63 63 0 1335,5 21,1 0,55 72 17 1368,8 17 0,64 74 10 1386,9 17,2 0,71 74 3 1404,8_ 16 0,58 72 14 1424,4 32,1 -0,49 51 100 1448,6 17,5 0,54 60 7 1482 17,7 0,61 67 7 1493,8 20 0,55 58 3 1499,9 17,6 0,76 86 10 1539,7 34,1 -0,66 30 97 1567 19,2 0,5 53 3 1573,8 27,8 0,49 7T 28 1579,5 22,9 -0,65 21 86 1585 18,1 0;79 93 14 1621,8 13,4 0,47 74 28 1644,4 20,8 0,63 63 0 1651,9 17,2 0,62 65 3 1689,7 32,2 0,47 53 7 1698,1 18,4 _ 0,74 98 24 1811,2 17,9 0,84 98 14 1819,7 20,4 0,47 53 7 1829,1 18 0,49 98 48 1851,1 17,8 0,74 81 7 1863,8 37 -0,43 47 90 186_7,2 18,6 0,8 84 3 1872,9 18,6 0,63 70 7 1878,5__17,3 0,49 56 7 1880_,1_37,5 -0,48 7 55 1895,1 _16,2 0,58 72 14 __1924,520,4 0,51 51 0 1943 _19,5 _ 0,79 86 7 1955 19,9 0,43 53 10 1977 12,7 -0,57 5 62 2039,1 18,6 -0,53 23 76 2042,1 17,7 0,7 77 7 2048 19,9 -0,6 40 100 2057,3 19,1 0,67 67 0 2133,3 21,5 0,56 70 14 2147 19,5 0,44 58 14 2174,9 27,8 -0,8 9 90 2233_,1_18,1 -0,52 7 59 2246,2 22,1 0,79 79 0 2249,1 18,7 -0,49 16 66 2279,5 22,5 0,5 53 3 2377,4 18,4 -0,79 0 79 2389,2 18,6 0,63 70 7 2405,6 17,8 0,58 58 0 2427,1 16,4 0,83 93 10 2483,4 21,6 -0,47 12 59 2502,2 19,2 0,57 67 10 2518,7 18,8 0,52 56 3 2540,4 16 0,68 74 7 2562,9 19,1 -0,52 37 90 2566,7 13,9 0,71 74 3 2608,3 21,8 0,65 86 21 2621,5 16,5 0,69 72 3 2649,6 28,9 -0,5 12 62 2695,4 19,7 -0,59 37 97 2742,3 23,7 -0,62 35 97 2752,4_ 15,5 0,85 95 10 2755,3 23,6 0,8 84 3 2761,3 17,7 -0,4 12 52 2790,6 16,4 0,6 60 0 2799,7 20,4 -0,42 51 93 2825 20,8 -0,67 33 100 2838,7 20,3 -0,58 35 93 2936,8 16 0,67 67 0 3011,5 24,5 -0,63 37 100 3013,3 16,8 -0,48 14 62 3040,9 25,5 -0,69 28 97 3098,3 24,8 -0,57 5 62 3205,9 15,7 -0,57 5 62 3209,4 19 -0,73 9 83 3265,5 24 -0,69 21 90 32_81,1 27,3 -0,56 37 93 3287,4 25,2 -0,47 47 93 3303,5 28,7 -0,49 23 72 3333,2 14,1 -0,67 2 69 -5~-3359,6 26,2_ -0;71 5 76 3375,6 25,3 -0,54 5 59 3385,7 21,2 -0,56 37 _ 3402,3 17,8 -0,57 12 69 3405,3 21,6 -0,79 14 93 3416,7 26,4 -0,44 12 55 3432,5 25,6 -0,67 9 76 3502,8 14,8 -0,53 2 55 3582,9 14,2 -0,72 7 79 3841,4 14,9 -0,44 42 86 3969,1 18,1 _ 14 55 -0,41 3987,1 17,3 -0,62 28 90 4044,5 18 -0,42 16 59 4098,2 20,5 -0,51 28 79 4153,7 14,7 0,51 65 14 4240,6 14,8 0,61 81 21 4290,3 23,4 -0,63 9 72 .

4306,5 23,5 -0,56 2 59 4712,9 15,8 0,68 74 7 4748 14,7 -0,68 19 86 6171,4 23 -0,68 19 86 6186,7 23,3 -0,65 21 86 8764,7 12,8 0,45 86 41 9868,4 17,2 -0,63 9 72 10044,3 13,1 0,64 88 24 Table 13:
molecularmigration discriminationfrequenc weight time factor IgA
[Da] [min] MGN

816,7 16 -0,47 7 54 852,6 19,7 0,51 51 0 862,4 27,2 0,56 56 0 874,7 19,2 -0,43 42 85 943,6 17,5 -0,59 26 85 977,6 18 -0,5 12 62 994,5 18,3 -0,52 2 54 1004,6 22,4 -0,49 5 54 1040,4 19,5 -0,59 2 62 1060,7 17,4 -0,41 51 92 1099,8 17,5 -0,57 28 85 1108,6 17,3 -0,5 42 92 1143,6 30,2 0,45 60 15 1157,5 31,6 0,47 63 15 1179,6 31,6 0,49 72 23 1186,7 19,7 -0,49 5 54 1195,6 31,4 0,64 79 15 1198,8 17,7 -0,49 28 77 1203,7 19,3 0,45 60 15 1217,6 30,1 0,78 93 15 1219,7 23,7 0,49 72 23 1239,6 30,6 0,75 91 15 1252,7 20,5 -0,81 12 92 1255,6 29,4 0,49 72 23 1261,5 30,1 0,51 74 23 _1268,4 23 -0,51 26 77 1270,7 16,6 -0,47 7 54 1285,8 18 -0,46 47 92 1287,6 18,8 ~ -0,55 14 69 1311,8 17,9 -0,46 23 69 1335,5 21,1 0,41 72 31 13_40,6 16,7 -0,52 9 62 1343,1 18,5 -0,48 21 69 1350,8 19 -0,48 14 62 1365,7 21,2 -0,62 7 69 1377,8 17,1 -0,4_7 7 54 - _. _ -- 19'8 _O 7 69 1402,4 18,7 -0,52 2 54 1405,8 31,3 0,54 70 15 1424,8 14,7 -0,5 12 62 1446,7 32,7 0,44 67 23 1455,8 20,7 -0,7 7 77 1464,1 21,3 -0,55 7 62 1465,7 _19_,_4 -0,67 2 69 _ 147_0_,8 17,3 -0,47 7 54 1472 21,3 -0,53 16 69 1484,5 17,5 -0,73 12 85 1486,4 19,5 -0,58 12 69 1514,6 19,4 -0,49 5 54 1519,1 13,4 -0,5 12 62 1523,7 33 0,65 95 31 1539,6 21,8 -0,62 30 92 1545,8 33,5 0,61 84 23 1556,7 19,6 -0,85 0 85 1561,8 33,3 0,55 93 38 1561,9 19,8 -0,57 5 62 1573,8 27,8 0,61 77 15 1579,5 22,9 -0,41 21 62 1596,9 18,3 -0,6 9 69 1603 19,1 -0,55 7 62 1611,6 32,9 0,51 51 0 1627,6 19,6 -0,52 2 54 1637,8 19,3 -0,6 9 69 1651,8 34 0,59 74 15 __1707,6 19,7 -0,42 12 54 1726 20,1 -0,6 9 69 1775,9 20,8 -0,42 12 54 1782,3 18,9 -0,42 35 77 1787,7 19,3 -0,48 14 62 1791,3 19,3 -0,56 21 77 1793,1 23 -0,61 16 77 1799,3 18,7 -0,54 0 54 1845,3 20,1 -0,68 9 77 1876,8 19,2 -0,52 33 85 1887,6 21,5 -0,45 9 54 1891,2 18,7 -0,59 2 62 1936,5 21,6 -0,46 23 69 1968,5 27,3 -0,5 12 62 _1971,3 22,2 -0,5 12 62 1988,9 18,9 -0,42 12 54 2014,9 18,1 -0,69 23 92 2025,9 21,7 -0,49 5 54 2063,8 17,7 -0,49 51 100 2085,9 21 -0,45 9 54 2113 18,6 -0,42 12 54 2129,1 16,6 -0,57 5 62 2135,3 18,1 -0,68 9 77 2147 19,5 -0,42 58 100 2154,1 21,2 -0,44 33 77 2159 23,1 -0,47 37 85 2166,6 20,1 -0,48 14 62 2171,7 21,1 -0,41 21 62 2178,4 14,9 -0,52 9 62 2183,5 16,3 -0,47 7 54 2229,5 20,2 -0,7 7 77 2246,2 22,1 0,48 79 31 2290,5 20,1 -0,41 21 62 2292,2 20,6 -0,47 7 54 2309,7 16 -0,52 2 54 2325,2 18,2 -0,53 16 69 2361,6 17,3 -0,49 5 54 2377,4 18,4 -0,54 0 54 2407,5 19,3 -0,45 9 54 2421,1 16,1 -0,62 0 62 2464,4 19,8 -0,69 23 92 2466,6 17 -0,48 21 69 2475,8 18,8 -0,64 21 85 2483,4 21,6 -0,73 12 85 2493,3 14,9 -0,57 28 85 2522,4 16,3 -0,41 28 69 2547,1 17,9 -0,55 14 69 __25 17,7 -0,72 5 77 53,7_ _ 20,3 -0,45 16 62 2573,5 --2586,7 1$'5 _p,59 2 62 2599,2 21 -0,68 9 77 2608,3 21,8 0,48 86 38 2669,1 18,4 -0,52 2 54 2676 20,6 -0,55 14 69 2681,5 _20,1 -0,42 12 54 2684,2 _19_,4 _ 7 62 -0,55 2687,5 19,2 -0,59 2 62 2755,3 23,6 0,53 84 31 2807,6 17,3 -0,47 7 54 2810,5 18,1 -0,5 12 62 2_83_1,2 19 -0,43 19 62 2847,7_ 16,5 -0,5 35 85 _2914,8 17 -0,45 40 85 2959,7 16,6 -0,47 7 54 3030 16,7 -0,44 26 69 3062,1 17,9 -0,54 23 77 3441,6 25,4 0,62 70 8 3478,6 27,6 0,78 86 8 3495,5 25,8 0,71 79 8 3841,4 14,9 -0,43 42 85 4183,6 16,3 -0,45 9 54 4479,4 14,8 -0,45 9 54 4483,2 16,2 -0,47 7 54 _4527,6 16,3 -0,5 12 62 4566,6__ 16,6 -0,52 2 54 4594,4 14,2 -0,45 9 54 8053,8 12,9 -0,44 26 69 Table 14:
mass CE frequency mass CE_t frequency t [%] [%]

[Da] [min]controlFSGS MCD MGN [Da [min]controlFSGS MCD MGN

3012,0939,45100 60 94 72 1028,57.37,7998 40 69 22 1539,6750,20100 90 100 89 876,4148,8998 70 38 67 2249,1933,82100 80 83 2205,0336,9498 70 88 83 3152,5538,22100 60 39 3402,4033,83_98 50 94 56 3360,0944,33100 60 72 2377,6032,0698 80 94 83 3001,9748,35100 100 89 2175,0344,2798 80 100 100 2257,1946,60100 60 67 2385,4545,4798 80 81 94 2563,4232,22100 90 72 2046,9945,3998 50 56 50 2158,9846,70100 90 89 2409,9032,5498 100 94 94 3287,9743,92100 90 89 3433,2844,4698 70 56 56 3385,7636,60100 100 72 1545,7554,7298 90 100 89 3271,8044,05100 80 61 2736,3132,3097 100 94 89 2007,6933,06100 90 89 3723,3332,4897 20 50 22 1194,6139,46100 70 88 83 1737,7641,2997 90 88 89 1265,6240,371_00 70 94 72 1378,5445,4597 60 81 56 1435,6939,91100 90 94 89 2854,4143,8097 50 75 56 1261,5349_,63100 80 88 61 2068,5441,069T 80 81 61 1438,5637,63100 100 100 100 2663,3636,3897 80 88 83 1446,5052,53100 80 94 67 2085,5039,2197 100 94 94 3265,7742,28100 80 75 78 2682,4935,0397 90 75 89 3121,3642,46100 50 75 44 1046,5738,6397 20 38 6 1911,1437,40100 90 100 94 2994,6140,6397 90 88 72 1321,9141,10100 70 69 50 2583;9843,7597 30 62 28 2695,4935,27100 70 88 78 2129,4835,1497 60 50 17 1235,5941,42100 60 69 50 981,56 37,3997 50 81 56 2799,9437,08100 80 88 83 879,55 26,9597 60 94 22 2169,7539,56100 100 100 94 2394,2936,3297 100 100 94 1224,7433,57100 50 94 33 3986,9830,.4697 50 69 44 1451,6741,11100 100 100 83 2483,5838,7497 90 81 78 3479,3248,53100 70 75 17 1523,7354,2997 90 1 89 2649,9445,91100 90 75 78 1889,7646,3 97 _ _ 39 2687,3641,87100 60 75 61 1507,64_ 97 90 100 89 54,43 3458,5244,64100 90 94 72 3209,2234,2797 30 81 33 3442,8442,54100 80 94 56 3022,8233,8297 40 62 61 2048,1933,07100 40 81 61 1765,1735,5097 90 88 94 2679,4634,99100 50 94 67 1367,673,27 97 90 94 94 2227,3438,28100 70 62 83 2726,38_ 97 100 88 _ 40,38 100 1239,5250,23100 100 100 78 1179,5752,1797 80 100 83 3098,8042,63100 60 81 56 1651,8655,1597 90 100 78 2839,0735,41100 80 88 83 3376,2445,'1797 50 88 67 3417,1245,12100 70 81 61 3293,1554,2197 50 75 50 3426,2042,48100 70 88 72 1579,5039,4397 100 94 94 3041,1645,04100 80 81 39 3474,2743,3795 70 75 67 1508,7041,2698 90 94 61 2848,8336,3395 70 75 44 1462,6753,5898 70 88 50 3319,2846,2295 50 62 39 3280,9636,7698 20 50 22 1000,5233,9695 40 44 28 1877,3329,6298 100 100 100 3281,9749,4495 60 50 56 2742,2542,2598 90 75 89 1885,7457,4795 70 75 28 3092,7143,8698 90 81 78 3556,9234,8595 100 75 78 2196,6645,4598 80 100 89 1609,1742,6095 100 94 89 6187,5539,7898 60 94 67 2767,4131,3995 40 69 56 2825,4236,5498 __50 88 39 3108,8144,7095 50 75 56 1255,5549,8198 100 100 78 2233,0031,0695 30 69 56 2717,5634,4398 60 69 61 882,55 36,5595 60 31 72 3149,6741,6298 70 88 50 1680,1637,3295 100 94 100 1195,5351,7698 70 94 83 1673,8054,59g5 80 94 61 3496,0243,8598 90 94 61 2336,7842,4795 70 94 89 1561,6_954,1798 90 100 83 1217,6448,5495 100 94 83 1250,6341,9798 70 100 89 1489,4942,2195 90 94 72 3295,7738,3698 50 50 _33 2442,0646,8595 70 81 67 3405,6837,8498 40 62 17 2279,0647,1695 70 69 44 1578,0152,5398 70 75 50 4748,5125;3895 50 38 33 1134,5837,1198 90 94 94 1766,8435,1595 100 100 100 Table 15:
Frequency FrequencyFrequencyFrequency Mass CE-timeHealthy FSGS MCD MGN
Da min 1435,6932,7 94 86 100 7 1282,3929,3 69 29 29 0 3531,0126,9 69 0 0 0 5801,9413,3 69 0 7 7 Table 16:
health vs, renal atients _ mass Da _ .,_- _._- CE time min -909,4 40,3 1159,6 39,0 1338,7 47,2 1686,8 38,2 1847,8 57,0 1966,3 25,1 1990,8 47,3 2146,3 25,8 2432,2 38,3 2465,0 22,8 3707,0 31,g Table 17:
MGN vs. MCD
Mass CE t 879,6 26,9 - SS
1279,7 38,3 1341,8 33,1 1404,9 29,4 1569,8 48,3 1574,8 33,9 1605,9 23,7 252_7,340,8 15112,933,1 Table 18:
MCD vs.
FSGS

Mass CE t 1199,6 31,0 1826,9 50,8 2077,3 35,8 2258,9 33,6 12918,0 42,2 Table I9:
MGN
vs.
FSGS

Mass CE
t 2312,5 22,9 2453,6 32,0 2639,6 45,2 9182,0 17,1 Table 20:
mass CE time mass CE
Da ~ %health% MGN Da time %health% MGN
min [min 4098,240,1 100 0 1933,0241,5 100 12 3685,935,9 100 0 1889,8249,3 100 12 3531,342,9 100 0 1636,6946,8 _ 12 3359,748,4 100 0 1579,7647,3 100 12 3287,447,4 100 0 1438,6645,4 100 12 3265,351,6 100 0 1321,5945,8 100 12 3098,546,9 100 0 1255,5353 100 12 3041,346,5 100 0 1200,5353,4 100 12 3011,346,5 100 0 2427,4327 12 100 2742,245,8 100 0 1829,0933,8 12 100 2563,234,5 100 0 4627,0128,7 0 88 2483,544,5 100 0 2621,4229 0 88 2385,250,4 100 0 1942,5734,8 0 gg 1893,1 42,5 100 0 1867,0633,8 0 88 1639,9 47,5 100 _ 0 1759,9232,5 _ 88 1609,7 47,3 100 0 1460,8339,8 _ 88 y 0 1580,9 41,3 100 0 3013,3636,6 88 12 1508,7 46,6 100 0 2838,9 39,8 88 12 1489,6 46,2 100 0 2710,3152,8 88 12 1424,7 56 100 0 2395,0440,4 88 12 1407,6 54,6 100 0 1876,9137,2 88 12 1160,6 52,7 100 0 1863,8659,2 88 12 981,53 41 100 0 1651,8156,5 88 12 980,54 38 100 0 1561,5656,1 88 12 876,4 52,2 100 0 1523,7256,1 88 12 2752,9 29,3 0 100 1473,6646,4 88 12 6171,1 43,4 88 0 1261,4953,2 88 12 3851,9 41,2 88 0 1195,5 54 88 12 3706,8 35,2 88 0 10047 22,3 12 88 3634,2 43,6 88 0 4713,9428,8 12 88 3631,3 36,3 88 0 4241,4126,7 12 88 3478,9 47,9 88 0 1811,1334,6 12 88 3376,3 48,5 88 0 1753,9832,7 12 88 3338,2 38,6 88 0 1698,0634,1 12 88 3292;7 56,7 88 0 1584,9132,7 12 88 3280,6 42,2 88 0 4353,6233,6 75 0 3271,5 47,3 88 0 4102,4545,2 75 0 3248,5 47,2 88 0 4044,5834,1 75 0 2849,2 39,4 88 0 3987,4834,8 75 0 2736,4 39,3 88 0 3947,2236 75 0 2682,1 37,3 88 0 3589,6541,3 75 0 2642,6 44,7 88 0 3433,1248,6 75 0 2584,3 51,9 88 0 3416,9248,6 75 0 2257,1 50,3 88 0 3295,5342 75 0 2204,9 44 88 0 3261,5535,6 75 0 2196,9 49,9 88 0 3258,5237,8 75 0 2039,2 35,8 88 0 3193,4837;3 75 0 1680,8 47 88 0 3152,6 40,3 75 0 1635,8 56,8 88 0 3092,0847,6 75 0 1539,7 46,3 88 0 2863,2540,6 75 0 1423,7 54,4 88 0 2854,5552,4 75 0 1422,5 55 88 0 2698,3737,2 75 0 1353,7 43,2 88 0 2548,4237,7 75 0 1046,6 42,6 88 0 2464,0750,8 75 0 3969,5 34,4 100 12 2406,9850,6 75 0 3496,1 47,1 100 12 2279 50,2 75 0 3442,2 47,9 100 12 2233,0235,7 75 0 3405,4 42,4 100 12 2226,9743 75 0 3385,6 41,5 100 12 2019,9741,1 75 0 3281,7 53 100 12 1991,9536,2 75 0 3209,4 37,1 100 12 1849,8541,1 75 0 ~ 2799,942,4 100 12 ~ 1768 48,7 75 ~ ~ I 95 ~
~

2378 38,8 100 -- 12 1755,0248,2 75 0 ~

2170 42,6 100 12 1737,7848,2 75 0 2008 37 100 12 1462,6356,1 75 0 1949 41,5 100 12 1446,656 75 0 1425,7841,6 ~ 0 -- ~~----Table 21:
mass CE
Da time %health% MGN
min 1405,6 55,7 75 0 1389,6 55,3 75 0 1322,6 45,4 75 0 1262,6 56,4 75 0 1246,6 55,6 75 0 1224,8 35,4 75 0 1141,7 41,6 75 0 1028,6 41,9 75 0 946,43 50,5 75 0 3723,1 35,5 100 25 3458,2 48,2 100 25 3001,8 51,8 100 25 2825,3 40,8 100 25 2695,3 39,1 100 25 2679,2 39,2 100 25 2410 39,6 100 25 2394 39,3 100 25 2048 35,9 100 25 1911,1 41,6 100 25 1545,7 57,3 100 25 1507,7 57,3 100 25 1467,8 41 100 25 1451,7 46,4 100 25 1435,7 46,3 100 25 1265,6 44,6 100 25 1250,6 45,7 100 25 1239,4 53,7 100 25 1235,6 44 100 25 1217,6 53,3 100 25 1194,6 44,1 100 25 1179,5 55 100 25 1716 32,1 25 100 4827,2 29,3 0 75 2937,4 29,6 0 75 2057,4 37 0 75 1851,1 33,8 0 75 1680,1 33,6 0 75 1517,9 30,2 0 75 1483,9 32,5 0 75 1481,9 33,8 0 . 75 1404,8 29 0 75 1398,8 34,1 0 75 1367,6 56,1 88 25 1157,6 54,9 88 25 3474,3 47,9 75 12 3402,5 37 75 12 2761,4 34,7 75 12 2644,1 33,5 75 12 2587,2 34,9 75 12 2579,7 50,5 75 12 2579,7 41,4 75 12 2069,1 49,5 75 12 2047 49,5 75 12 1170,6 46 75 12 1386,8 32,3 25 88 8766,7 21,6 12 75 4154,4 26,4 12 75 3842,8 25,7 12 75 1873 33,9 12 75 1566,9 33,2 12 75 1499,9 33,7 12 75 1368,8 31,6 12 75 1285,7 31,1 12 75 1108,6 32,2 12 75 1099,6 31,2 12 75 1060,6 31,6 12 75 Table 22:
healthy, disease, time mass Da fre uenc fre uenc t a min 22,9 834,5 0,10 3% 54% Diabetes os.
3,05 22,9 869,4 0,17 14% 63% Diabetes os.
3,03 24,2 874,5 0,09 28% 66% Diabetes os.
1,89 22,2 907,5 ~- 0,13 0% 41 % Diabetes os.
2,19 29,0 910,5 0,09 15! 47/~ Diabetes os.
2,35 22,9 947,6 0,22 17% 51 % Diabetes os.
3,18 26,8 950,5 0,12 0% 24% Diabetes os.
2,98 23,2 995,6 0,14 23% 50% Diabetes os.
4,87 27,4 1082,6 0,16 0% 44% Diabetes os.
3,59 32,3 1096,5 0,14 10% 51 % Diabetes os.
1,99 26,8 1176,6 0,13 21 % 59/~ Diabetes os.
3,85 22,3 1222,8 0,22 17% 56% Diabetes os.
3,45 30,6 1236,6 0,11 24% 59% Diabetes os.
3,31 52,6 1285,0 0,09 14% 54% Diabetes pos 4,80 ~
~

28,8 1332,7 0,20 23% 55% Diabetes pos.
3,98 49,8 1332,8 0,16 8% 38% Diabetes os.
4,72 26,7 1355,8 0,15 17% 56% Diabetes os.
2,79 24,6 1386,8 0,14 53% 77% Diabetes os.
2,84 26,8 1403,7 0,21 8% 46'% Diabetes os.
3,26 17,8 1405,9 0,15 14% 56% Diabetes os.
4,12 31,5 1442,7 0,27 15% 55% Diabetes os.
3,71 32,1 1449,8 0,14 41% 85% Diabetes os.
3,38 31,3 1592,4 0,38 3% 46/ Diabetes os.
5,27 43,4 1783,4 0,30 33% _ Diabetes os.
4,41 63%

29,4 1789,2 0,39 28% 75% Diabetes os.
3,08 38,4 1818,9 0,21 28% 67% Diabetes os.
1,09 37,7 1821,4 0,39 14% 56% Diabetes os.
1,04 24,4 1829,2 0,23 45% 81 % Diabetes os.
2,55 51,1 1854,7 0,41 14% 54% Diabetes os.
4,11 37,6 1856,8 0,48 33% 56% Diabetes os.
3,30 24,7 1872,9 0,35 43% 72% Diabetes os.
2,63 28,3 1949,5 0,32 17% 73% Diabetes os.
3,47 31,6 1955,1 0,32 55% 79,r Diabetes os.
2,90 31,3 1971,0 0,45 20% 54% Diabetes os.
3,00 37,8 2032,0 0,30 25% 60% Diabetes os.
2,40 30,9 2061,4 0,58 10% 38.% Diabetes os.
4,69 33,8 2092,2 0,46 18% 45% Diabetes os.
3,76 27,7 2185,6 0,46 10% 36% Diabetes os.
4,43 32,9 2189,4 0,34 14% 54% Diabetes os.
1,48 39,6 2229,4 _+ 0,485% 39% Diabetes os.
5,31 24,5 2229,9 0,33 25% 63% Diabetes os.
5,14 28,3 2502,9 0,56 20% 48% Diabetes os.
3,30 24,9 2621,6 0,97 20% 45% D
4,84 iabetes os.

37,5 2669,8 0,39 23% 67rb _ 4,52 _ Diabetes pos.

20,8 2752,2 0,76 35% 64% Diabetes os.
4,47 24,9 27_95,7 0,96 13% 40% Diabetes os.
4,31 48,2 3246,1 0,43 0% 30ro Diabetes os.
3,61 20,9 3844,0 0,52 3% 54% Diabetes os.
3,33 21,9 4961,5 0,89 10% 40% Diabetes os.
2,62 18,6 5497,0 ~ 0,66 18% 42% Diabetes os.
2,91 20,4 808,4 0,10 58% 9% Diabetes ne .
2,20 45,3 897,5 0,09 48% 7/n Diabetes ne .
2,03 31,4 929,5 0,11 98% 46% Diabetes ne .
1,08 41,2 946,4 0,10 85% 36% Diabetes ne .
1,41 28,0 980,5 0,07 85% 31 % Diabetes ne .
1,04 26,7 1000,5 0,09 83% 41 % Diabetes neg.
2,26 27,8 1008,5 0,10 95% 4 Diabetes ne .
1,51 1 %

29,3 1012,5 -~ 0,1063% _ Diabetes ne .
2,55 17%

43,6 1047,5 0,11 90% 26% Diabetes ne .
2,03 25,0 1052,6 0,08 45% 4% Diabetes ne .
3,91 37,4 1066,5 +_ 0,1458% 13% Diabetes ne .
5,63 22,8 1075,5 0,13 68% 26/~ Diabetes ne .
1,78 28,9 1088,6 0,15 65% 21 % Diabetes neg 3,89 ~

44,4 1106,5 0,11 80% 18% Diabetes ne .
2,06 34,1 1107,5 0,10 ____88% _ Diabetes ne .
1,80 35%

42,8 1120,5 0,06 60% __ Diabetes ne .
3,26 14'%

29,1 1134,6 0,10 95% 49% Diabetes ne .
2,26 28,2 1137,7 0,11 _ 70% 24~% Diabetes ne .
3,00 45,5 1139,5 0,20 83% 22% Diabetes ne .
2,34 32,9 1159,6 0,11 80% 27% Diabetes ne .
1,25 23,3 1180,5 0,16 50% 9% Diabetes ne .
4,17 _ v 43,8 1200,6 0,11 95% 50! Diabetes ne 2,08 .

27,2 1204,6 0,17 60% 17% Diabetes neg 3,22 44,9 1209,5 0,09 83% 17~/0 Diabetes ne .
2,53 47,8 1224,6 0,12 75% 19% Diabetes ne .
2,73 25,6 1246,7 0,15 73% 30% Diabetes ne .
2,43 47,9 1268,6 0,09 68% 25t Diabetes ne .
2,66 43,9 t 1277,5 0,10__70% 28% Diabetes ne .
1,80 46,0 1278,5 0;09 58% 10% Diabetes ne .
2,69 33,1 1282,6 0,13 62% 7% Diabetes ne .
1,82 29,3 1331,7 0,18 65% 12% Diabetes ne .
3,88 45,9 1405,5 0,33 93% 45% Diabetes ne .
4,78 44,4 -~ 1423,6 0,16 60% 20JO Diabetes ne .
3,90 19,2 1484,8 0,19 68% 13% Diabetes ne .
3,40 36,9 1609,6 0,13 85% 13% Diabetes ne .
2,02 38,9 1639,7 0,27 63% 19% Diabetes ne .
3,78 33,2 1662,9 0,21 62% 5% Diabetes ne .
3,34 35,8 _ 66% 10% Diabetes ne .
2,19 1664,6 0,29 36,2 1666,6 0,34 75% 29io Diabetes ne .
4,78 35,9 1678,1 0,44 60% 18! Diabetes ne .
2,98 37,3 1716,8 0,23 73% 19% Diabetes ne .
2,99 46,5 1717,5 0,37 79% 15~~ Diabetes ne .
4,38 37,9 1746,0 0,33 83% 34% Diabetes ne .
4,18 25,1 1817,6 0,27 65% 8% Diabetes ne .
2,25 34,2 1823,4 0,47 73% 30% Diabetes ne .
3,95 29,1 1849,8 0,30 100% 56/~ Diabetes ne .
3,59 49,3 1914,1 0,36 88% 38% Diabetes ne .
4,49 44,2 1916,7 0,33 69% 10/> Diabetes ne .
4,23 39,8 2030,8 _+ 0,3593% 38% Diabetes ne .
2,19 31,9 2118,9 0,21 73% 14% Diabetes ne .
1,61 41,2 2179,3 0,42 58% 17% Diabetes ne .
2,45 20,1 2219,0 0,26 53% 13% Diabetes ne .
2,78 25,8 2256,9 0,47 85% 26% Diabetes neg.
2,70 45,1 2273,4 0,42 79% 22% Diabetes ne .
5,23 40,7 2279,0 0,33 90% 20% Diabetes ne .
1,90 26,8 2320,2 0,55 78% 34% Diabetes ne .
3,73 23,6 2332,2 0,35 53% 11 % Diabetes ne .
3,10 44,5 2345,6 0,46 75% 34% Diabetes ne .
3,08 25,7 2384,5 0,63 65% 21 % Diabetes ne .
5,16 38,5 2423,9 +_ 0,4188% 29% Diabetes ne .
3,62 34,2 2429,9 0,51 65% 18% Diabetes ne .
2,92 23,3 2443,3 0,46 66% 5% Diabetes ne .
2,54 41,7 3,722548,1 0,57 _ 69% _ Diabetes ne .
15%

27,3 4,772548,3 0,66 83% __ Diabetes ne .
_ 35%

43,6 2,082548,3 0,23 95% _ Diabetes ne .
41 %

24,0 3,112581,5 0,47 60% 13% Diabetes ne .

24,0 2,702587,4 0,40 80% 26% Diabetes ne .

41,7 3,062606,8 0,55 78% 35% Diabetes ne .

31,3 4,922636,4 0,48 72% 12% Diabetes ne .

25,5 -~ 2644,2 0,41 88% 33% Diabetes ne .
3,62 29,2 1,072654,0 0,37 66% 0% Diabetes ne .

29,8 3,502698,2 0,63 90% 29% Diabetes ne .

43,0 2,262710,5 0,37 79% 5~% Diabetes ne .

25,1 1,642761,3 0,35 88% 44% Diabetes ne .

31,3 2,792808,5 0,56 79% 22% Diabetes ne .

42,0 3,222876,5 0,48 62% 7% Diabetes ne .

33,7 3,342898,7 0,50 85% 43~o Diabetes ne .

42,2 2,682908,1 0,53 72% 17% Diabetes ne .

35,4 2,632917,6 0,58 72% 12% Diabetes ne .

35,4 0,772978,1 0,49 85% 35to Diabetes ne .

36,1 1,422994,6 0,80 83% 24% Diabetes ne .

43,5 2,993023,4 0,65 93% 34% Diabetes ne .

44,4 3,353045,2 0,61 69% 12% Diabetes ne .

22,9 3,473076,4 t 0,96 66% 7% Diabetes ne .

35,7 1,993082,3 0,43 73% 22% Diabetes ne .

33,6 3,533136,8 0,61 95% 47o Diabetes ne .

21,7 3,143154,8 0,44 55% 10~o Diabetes ne .

26,5 1,923193,7 0,53 78% 32% Diabetes ne .

24,4 3,023206,3 0,72 66% 7% Diabetes ne .

28,2 2,803250,9 0,71 63% 18% Diabetes ne .

48,2 3,463293,2 0,74 93% 39% Diabetes ne .

31,4 1,603295,7 0,33 95% 40~~ Diabetes ne .

27,2 3,583338,4 0,79 80% 34% Diabetes ne .

37,3 2,113381,6 0,63 78% 26% Diabetes ne .

27,6 2,493452,1 0,49 58% 15/~ Diabetes ne .

37,3 1,503463,0 0,83 72% 15% Diabetes ne .

19,6 2,893583,4 0,75 79% 20% Diabetes ne .

34,0 2,553634,4 0,74 86% 29% Diabetes ne .

37,7 2,613681,8 1,38 55% 14% Diabetes ne .

25,5 2,253686,2 0,60 86% 20% Diabetes ne .

36,0 3,893735,7 0,57 70% 28% Diabetes ne .

30,3 1,583852,3 0,56 83% 41 % Diabetes ne .

29,6 1,464098,4 0,59 93% 20% Diabetes ne .

28,8 1,185428,8 0,67 70% 19% Diabetes ne .

33,1 0,696187,5 1,13 83% 10% Diabetes ne .

26,0 4,826212,0 1,41 75% 26% Diabetes ne .

23,3 2,199868,8 1;33 66% 0% Diabetes ne .

21,7 5,12830,5 0,11 4% 40% Ne hro ath os.

32,4 1,83866,4 0,11 0% 40% Ne hro ath os.

30,6 3,07909,5 0,13 11 % 40% Ne hro ath os.

32,8 3,14937,5 0,11 14% 73% Ne hro ath os.

24,9 952,5 0,16 _ 11% 40% Ne hroathos.
2,97 32,1 1033,5 0,11 _ 5% 40% Ne hroathos.
2,44 ___-24,4 1060,6 0,16 17% 68% Ne hroathos.
2,87 27,5 1131,6 0,16 20% 68% Ne hroathos.
2,86 33,4 1181,6 0,15 22% 73% Ne hroathos.
3,48 33,0 1203,6 0,14 9% 50% Ne hroathos.
2,52 26,5 1211,6 0,14 14/~ 40% Ne hroathos.
3,68 33,1 1219,6 0,15 18% 40% Ne hroathos.
0,91 32,8 1225,6 0,13 12% 40% Ne hroathos.
3,30 30,7 1297,7 0,20 31 % 82% Ne hro os.
3,18 ath 34,1 1333,7 0,23 9% 40% Ne hroathos.
2,05 44,7 1337,5 0,20 19% 59% Ne hroathos.
4,06 27,9 1398,8 0,36 29% 77% Ne hroathos.
4,19 21,3 1423,7 0,49 6% 50% Ne hroathos.
5,08 28,1 1439,8 0,19 19% 68% Ne hroathos.
4,95 24,5 1466,0 0,27 9% 77% Ne hroathos.
2,42 27,5 1482,0 0,42 33% 40% Ne hroathos.
4,93 29,8 1482,9 0,28 18% 40% Ne hroathos.
4,43 24,3 1483,7 0,28 26% 91 % Ne hroathos.
2,65 24,6 1500,0 0,20 38% 86l Ne hroathos.
1,98 24,6 1553,1 0,28 14% 64% Ne hroathos.
2,90 29,0 1556,7 0,45 26% 73% Ne hroathos.
4,83 24,2 1567,0 0,22 26% 86t Ne athos.
2,48 hro 28,8 1596,9 0,31 21 % 86% Ne hroathos.
4,53 24,5 1652,8 0,25 14% 59% Ne hroathos.
2,43 26,3 1669,8 0,37 20% 64.% Ne hroathos.
2,63 33,1 1729,2 0,36 6% 45! Ne hroathos.
3,22 30,5 1744,4 0,46 16% 59% Ne hroathos.
4,11 25,1 1754,4 0,41 53% 95% Nee~hropathypos.
3,42 24,2 1776,0 0,27 9% _ Nephropathy ~os.
1,56 . 50/

18,5 1791,0 0,38 7% _ Ne hroathos.
3,55 40/

32,2 1792,9 t 0,31 28% 40% Ne hroathos.
5,38 9,7 2,541799,8 0,29 0% 40% Ne hroathos.

25,3 1810,9 0,38 43% 91 % Ne hroathos.
2,89 24,6 1851,1 0,21 43% 95% Ne hro os.
2,34 ath 27,2 1867,3 0,42 38% 91 % Ne hroathos.
4,46 25,0 1966,0 0,53 16% 40/' Ne hroathos.
3,97 28,7 1982,8 0,57 11 % 40% Ne hroathos.
3,08 29,5 1986,3 0,36 15% 64/n Ne hroathos.
5,53 23,3 2045,9 0,32 32% 40% Ne hro os..
4,46 ath 33,7 2115,1 0,53 30% 40% Ne hroathos.
3,16 20,5 2177,1 0,37 9% 40% Ne hroathos.
2,78 18,1 2241,6 0,41 9% 59% Ne hroathos.
4,24 21,2 2250,7 0,38 23% 64/> Nephropath os.
2,49 27,5 2258,7 0,49 9% 59% Nephroathos.
2,53 20,0 2356,4 0,41 13% 59% _ hroathos.
3,30 Ne 28,1 2391,4 0,42 13% 64% Ne hroathos.
3,95 25,7 2406,1 0,57 20% 77% Ne hroathos.
4,85 X22,8 2423,2 0,53 14% _ Ne os.
4,28 ~ ~64% hro ~ ath 21,9 2427,3 0,40 31 % 91 % Ne hroathos.
4,45 19,2 2465,1. 0,62 9% 77% Ne hroateos.
4,24 _-25,4 2493,0 0,38 9% 50% Ne hroathos.
5,25 19,5 2494,0 0,66 12% 77'% Ne hro os.
4,66 ath 23,7 2494,9 0,49 7% 40% Ne hro os.
4,27 ath 24,4 2522,0 0,67 17% 82'% Ne hroathos.
5,51 20,1 2540,5 0,54 14% 68% Ne hroathos.
3,61 22,3 2593,5 0,30 7% 55% Ne hroathos.
4,72 20,0 2613,9 0,83 14% 55% Ne athos.
4,87 hro 35,1 2726,5 0,67 61 % 20% Ne hroathos.
1,62 25,0 2775,1 0,56 12% 40% Ne hroathos.
4,39 21,8 2790,7 0,55 19% 86% Ne hroathos.
3,78 25,9 2892,2 0,50 9% 50% Ne hroathos.
3,30 16,8 2919,0 0,26 2% 50% Ne athos.
2,72 hro 21,9 2937,0 0,49 13% 86% Ne hroathos.
3,23 20,0 2958,8 0,80 5% 59% Ne hroathos.
4,81 34,4 2962,0 0,54 12% 20mi Ne hroathos.
2,72 28,9 3059,7 0,78 30% 40% Ne hroathos.
3,56 28,3 3088,0 0,79 7% 20% Ne hroathos.
5,96 26,1 3369,2 0,73 21 % 40% Ne hroathos.
2,72 26,0 3483,4 0,95 30% 40% Ne hroathos.
2,89 24,5 4183,3 1,44 4% 40% Ne hroathos.
3,92 21,0 4241,0 0,62 29% 73% Ne hroathos.
5,35 23,4 4370,2 1,01 11 % 40~ Ne hroathos.
4,09 22,8 4527,6 0,67 1 % 45' Ne hroathos.
2,94 21,7 4713,6 0,44 7% 64% Ne hroathos.
3,00 24,6 7556,6 1,55 2% 40% Ne hroathos.
3,73 16,7 8055,1 2,10 12% 40% Ne hroathos.
5,54 13,2 8765,8 0,96 37% 82% Ne hroathos.
5,19 15,3 9181,0 1,28 10% 64% Ne hroathos.
4,97 14,0 10046,1 0,96 21% 77! Ne hroathos.
4,20 18,7 10208,0 1,24 2% 40% Ne hroathos.
5,50 17,4 f 10518,2 1,10 23% 64% Ne hroathos.
4,02 35,3 924,5 0,12 50% 0% Ne hroathne .
5,04 43,1 928,4 0,08 65% 14% Ne hroathne .
2,61 45,7 955,5 0,14 60% 5% Ne hroathne .
2,25 23,8 1010,6 0,09 67% 5% Ne hroathne .
2,94 31,2 1028,5 0,09 84% 32% Ne hroathne .
1,53 45,9 1041,4 0,10 57% 0/n Ne hroathne .
2,27 31,5 1046,5 0,09 87% 32/n Ne hroathne .
1,98 43,4 1047,5 0,12 68% 0/> Ne hroathne .
2,24 18,1 1050,7 0,12 60% 0% Ne hroathne .
4,34 32,9 1084,4 0,11 69% 18/<> Ne hroathne .
3,03 46,7 1125,5 0,12 63% 9% Ne hroathne .
2,63 46,3 1157,5 0,10 83% 32% Ne hroathne .
2,70 43,7 1160,5 0,07 72% 18% Ne hroathne .
1,70 44,5 1179,5 0,09 97% 36% Ne hroathne .
3,67 45,0 1191,6 0,09 60% 9% Ne hroathne .
2,24 46,2 1195,5 0,10 98% 32% Ne hro ne .
2,59 ath 44,2 1200,6 0,13 -_ 86% 0% Ne hroathne .
1,83 45,9 1223,5 0,10_,-80% 9% Ne hroathne .
2,04 44,5 1239,6 0,08 89% 0% Ne hroathne .
2,15 47,8 1246,6 0,11 60% 5% Ne hroathne .
3,08 46,8 1254,7 0,19 56% 5% Ne hroathne .
2,20 43,2 1261,5 0,16 91 % 36/~ Ne athne .
2,90 hro 48,6 1262,5 0,09 65% 0% Ne hroathne .
2,90 43,9 1277,6 0,11 67% 0% Ne hroathne .
2,16 36,7 1288,7 0,18 72% 23% Ne hroathne .
3,04 47,2 1292,5 0,14 67% 18% Ne hroathne .
3,17 47,8 1308,5 0,09 66% 0% Ne hroathne .
2,58 48,2 1321,6 0,11 53% 0% Ne hro ne .
2,67 ath 34,8 1321,7 0,23 98% 41 % Ne hroathne .
1,81 46,0 1351,7 0,15 63% 9% Ne hroathne .
4,93 47,7 1367,6 0,14 97% 23% Ne athne .
2,99 hro 37,8 1378,6 0,16 87% 36% Ne phro~athrune 2,93 .

47,5 1389,7 0,15 86% 18% Ne hropathy neg.
2,59 46,5 1407,8 0,20 79% 9% Ne hroathathne .
2,28 44,6 1422,1 0,33 70% 0% Ne hroathne .
4,84 45,4 1423,8 0,19 75% 0% Ne hroathne .
3,62 48,0 1424,7 0,16 95% 18% Ne hroathne .
2,97 47,6 1446,7 0,16 92% 23% Ne hroathrie .
3,40 46,5 1450,4 0,25 62% 9% Ne hroathne .
2,95 48,0 1462,6 0,17 97% 9% Ne hroathne .
2,95 35,7 1487,7 0,15 70% 18% Ne hroathne .
1,90 47,8 1490,6 0,12 72% 9l Ne hroathne .
2,35 49,2 1491,7 _+ 0,1281 % 14! Ne hroathne .
2,77 49,0 1507,8 0,17 99% 32% Ne hroafhne .
3,14 49,2 1523,7 0,11 97% 18% Ne hroathne .
2,86 48,6 +_ 1529,7 p,1 83% 9% Ne hroathne .
2,70 g 49,2 1539,7 0,19 98% 23% Ne hroathne .
3,26 49,0 1545,7 0,13 99% 23ro Ne~hro~a~neck.
3,19 49,8 1561,6 0,19 90% 18% Ne hro~athyneg.
2,76 48,4 1567,7 0,20 65% 9io Ne hroathne .
3,12 48,1 1573,7 0,27 63% 5im Ne hroathne .
2,66 48,5 1577,8 0,35 94% 9/~ Ne hroathne .
4,03 50,6 1587,1 0,34 65% 0% Ne hroathne .
3,40 48,6 1589,7 0,14 86% 18 Ne athne .
2,68 l hro 45,9 1591,7 0,30 79% _ Ne hroathne .
3,83 18%

49,3 1594,8 0,14 88% 14/u Ne hroathne .
3,22 48,8 1605,7 0,13 73% 18% Ne hroathne .
2,78 48,5 1611,7 0,14 73% 5% Ne hroathne .
2,81 46,3 1636,4 0,39 79% 23% Ne hroathne .
5,12 49,5 1651,8 0,19 99% 23% Ne hroathne .
3,37 45,2 1657,7 0,23 60% 5% Ne hroathne .
5,96 49,5 1673,8 0,14 95% 23% Ne hroathne .
3,33 49,6 1689,8 0,18 86% 0% Ne hroathne .
3,05 26,9 1706,8 0,30 78% 27% Ne hro ne .
3,18 ath 49,4 1734,4 0,40 65% ( 5% Ne ne .
2,84 ~ hro ' ath 49,2 3,171739,7 0,22 59% 5% Ne ne .
_ hro ath 45,1 +_ 1748,0 0,28 55% 5% Ne ne .
4,21 hro ath 44,2 4,711813,6 0,38 58% _ Ne ne .
5% hro ath 39;1 3,481817,0 0,29 85% 18% Ne hro ne .
ath 51,7 3,481841,0 0,23 59% 9% Ne hro ne .
ath 50,4 4,561848,2 0,43 58% 0% Ne hroathne .

51,5 2,941856,8 0,24 59% 5% Ne hroathne .

52,7 4,241863,8 0,31 88% 14% Ne hroathne .

52,7 3,921885,8 0,20 70% 5% Ne hroathne .

47,7 4,691902,1 0,33 75% 0% Ne hroathne .

50,6 3,951924,0 0,48 68% 0% Ne hroathne .

26,6 1,762048,5 0,44 86% 20% Ne hroathne .

25,8 1,392085,9 0,24 83% 32% Ne hroathne .

39,9 1,452087;8 0,34 72% 23% Ne hroathne .

52,8 4,092117,1 0,17 78% 9% Ne hroathne .

28,3 3,902129,7 0,42 63% 0% Ne hroathne .

40,4 1,532158,9 0,26 86% 32% Ne hroathne .

39,7 1,712174,9 0,36 97% 45% Ne hroathne .

32,6 1,792227,1 0,41 81% 23% Ne hroathne .

29,3 3,502249,0 0,41 92% 41 % Ne hroathne .

40,6 1,252257,1 0,35 94% 45~ Ne hroathne .

46,2 5,112273,5 0,38 71 % 18% Ne hroathne .

40,8 2,662296,0 0,40 63% 20% Ne hroathne .

40,9 3,322327,6 0,52 85% 36% Ne hroathne .

41,8 2,452343,3 0,43 77% 27% Ne hroathne .

40,8 1,312385,3 0,32 95% 45% Ne hroathne .

40,9 2,682471,5 0,52 69% 14% Ne hroathne .

41,5 2,642493,5 0,48 74% 18% Ne hroathne .

52,9 3,982570,4 0,27 71 % 5! Ne hroathne .

34,1 0,722642,8 0,40 86% 36% Ne hroathne .

36,1 2,562687,1 0,49 84% 23% Ne hroathne .

42,8 2,332710,6 0,46 88% 18% Ne hroathne .

50,6 4,732748,6 t 0,36 64% 0% Ne hroathne .

37,8 1,922986,6 0,55. 74% 23/p Ne hroathne .

23,3 2,073007,4 0,50 65% 9% Ne hroathne .

25,9 2,353038,3 0,70 46% 0/~ Ne hroathne .

46,0 2,913045,4 0,36 59% 5/> Ne hroathne .

53,3 4,053057,2 0,64 76% 9% Ne hroathne .

38,9 2,573109,0 0,57 88% 14% Ne hroathne .

41,9 3,553187,6 0,47 71 % 14% Ne hroathne .

26,6 1,153193,6 0,41 61 % 0% Ne h athneck.
ro 48,3 3,693223,8 0,41 88% 18% Ne _ athynet.
h~op 31,7 3,653265,1 0,64 93% 41 % Ne hroathne .

29,5 1,763291,0 0,52 81 % 23% Ne hroathne .

49,2 3,703293,1 0,43 91 % 14% Ne hroathne .

49,9 3,573315,0 0,45 67% 5% Ne hroathne .

43,3 2,043319,9 +_ 0,6686% 23% Ne hroathne .

49,1 3,353336,7 0,38 63% 9% Ne hroathne .

38,5 2,053359,9 0,42 _ _ ~ 98% 41 % Nephropathyneg 38,5 3360,1 0,65 - 98% 20'% Nehroathne .
1,92 38,5 3417,1 0,48 .,_ 95% _ Nehro athne .
2,03 _,_i _.-45%

38,5 3433,3 0,43 92% - Nehroathne .
1,09 41 %

51,6 3478,9 0,48 74% 5% Nehroathne .
3,50 31,7 3589,7 0,48 73% 18% Nehro ne .
2,29 ath ' 33,2 3633,4 0,95 80% 18% Nehroathne .
3,71 36,0 3636,6 0,73 58% 0% Ne athne .
3,18 hro 37,9 3719,5 0,61 67% 9% Ne~hroathne .
2,69 42,0 3739,7 0,99 73% 14% Nehroathne .
3,21 25,8 3947,3 0,67 92% 32% Nehroathne .
1,20 39,4 4006,6 0,49 62% 5% Nehroathne .
1,13 26,0 4044,9 0,56 78% 14% Nehroathne .
3,97 30,5 4070,4 0,48 57% 5% Nehroathne .
2,17 29,5 4098,6 0,52 86% 32% Nehroathne .
0,93 34,3 4102,5 0,50 77% 14t Nehroathne .
2,08 34,7 4290,7 0,52 76% 18t Ne athne .
0,63 hro 23,5 4405,8 0,54 51 % 0% Nehroathne .
1,61 30,4 4801,5 1,06 65% 0! Nehroathne .
1,31 32,4 4863,8 0,64 67% 5% Nehroathne .
1,31 29,5 5214,0 1,29 51 % 0% Nehroathne .
2,25 33,0 6172,0 1,57 65% 0% Nehroathne .
0,99 33,2 6187,8 0,75 95% 45J Nehroathne .
0,75 23,8 9869,7 1,06 69% 14% Nehroathne .
1,86 Table 23:
mi ration time dt min mass Da min 15,490396 ___0,1588048054,473633 15,803237 0,155143 8765,233398 16,034266 0,174906 1621,9104 16,185061 0,147871 9180,99707 16,645294 0,198704 10045,20703 17,663696 0,165531 10388,81348 17,980883 0,178564 10518,18457 19,917442 0,234131 9220,939453 20,34516 0,170572 1877,789429 20,479975 0,221246 3842,693604 20,519386 0,265078 4747,932617 21,465685 0,217493 4154,003906 21,480436 0,362197 2427,251709 21,804012 0,271715 4240,856445 22,221563 0,191069 4282,796387 22,777784 0,245503 3840;540527 24,304148 0,319715 7556,177734 24,579231 0,291986 879,519653 24Y813087 0,224198 1867,731689 25,283239 0,22054 2266,040771 26,177101 0,289898 2172,188721 26,773794 0,352887 2914,05542 26,81407 0,297343 962,591919 28,254925 0,581783 4353,585938 28,825331 0,258778 1250,62439 29,308136 0,852391 1060,239014 29,822325 0,595913 1682,720947 30,75272 0,175961 943,492859 30,762201 0,263861 1108,647949 30,926645 0,138075 1368,781738 31,305229 0,301605 3987,548828 31,433071 0,515308 1099,419434 32,165497 0,198377 3122,730713 32,222111 0,226858 1829,089966 33,427856 0,151562 2767,015625 34,053886 0,252424 1302,691772 34,15913 0,233032 3722,875977 34,557327 0,186137 2039,143433 34,681156 0,20976 3685,918213 35,30254 0,207782 2389,097168 35,502213 0,388916 3209,800293 36,314056 0,183495 980,526123 36,404907 0,145751 1008,513733 36,424831 0,150486 1000,48761 36,720509 0,128397 2717,472656 36,777012 0,164648 2663,246826 37,557594 0,165628 3556,580566 37,572525 0,185484 1743,890381 37;680653 0,160958 1134,580566 37,700241 0,171622 4097,981934 38,050472 0,156383 3152,361572 38,155159 0,217341 2825,309082 38,17057 0,432096 882,532654 38,281631 0,20781 996,190369 38,57658 0,370648 1425,324829 38,687305 0,15052 3385,513916 38,830559 0,056085 1352,824097 38,921108 0,150325 5000,982422 39,241917 0,178206 3775,720459 39,433277 0,235333 3405,60791 39,484215 0,140887 1046,52771 39,513248 0,093703 2154,053955 39,936756 0,195951 6171,129395 40,533363 0,158628 1194,581543 40,537457 0,221485 2205,064941 40,607231 0,426674 1235,384888 40,686531 0,122381 1265,634888 40,83009 0,191972 2642,264893 41,506096 0,161887 4159,304199 41,604115 0,217324 1250,585449 41,818069 0,163642 2742,253418 42,079609 0,266392 1463,643311 42,105633 0,172054 1489,658936 42,131275 0,184863 1473,643555 -6~-42,144161 __ Oi162_7161451, 710938 42,573879 0,234118 _,-_ 098,450928 42,636433 0,041732 _ 1487,660034 42,811199 0,246696 1579,670776 42,940624 0,1884 3121,243164 43,093792 0,106392 3271,523438 43,115334 0,607341 1834,878052 43,46143 0,193155 3442,135498 43,494144 0,20218 3495,841797 43,549488 0,217899 3473,905029 43,740391 0,12795 3108,919434 44,191006 0,18629 3359,583496 44,230297 0,233319 3416,526611 44,934914 0,127421 1991,917114 45,538418 0,214716 2197,337158 45,675098 0,12333 1889,864502 46,313114 0,259721 2385,597168 47,216648 0,168651 2649,602539 47,279705 0,127824 2343,072998 47,526871 0,19233 2584,635986 48,441795 0,239347 1160,526001 48,804813 0,251244 1261,53125 49,519478 0,243133 1274,625244 51,416531 0, 33207 1195, 518677 51,492035 0,213235 1211,559204 51,657627 0,822884 1223,348633 53,168346 0,293424 1351,643433 53,240913 0,216809 1367,655151 53,259499 0,15916 1770,30481 54,59832 0,234281 1507,742432 55,038143 0,329349 1594,211426 57,475471 0,325805 1840,810547 58,191887 0,1' 29 2021,900879 58,898354 0,484288 2608,239746 60,082333 ( 0 507699 1863,939453 ~

Table 24:
mi ration tirnedt min mass Da min 12,295616 0,0_92835 8053,516 12,33161 9 0,12201 1621,946 12,508785 0,139706 8765,729 12,696615 0,122507 9181,114 12,906662 0,115952 10046,58 13,103853 0,041984 2427,001 14,332394 0,144029 4153,814 14,426023 0,131007 4240,702 14,496774 0,385605 3841,615 14,585806 0,105399 4282,281 15,094264 0,132582 879,5324 15,123884 0,069059 1868,033 15,236325 0,136994 7555,679 15,641728 0,159929 962,6218 16,194395 0,167525 1060,664 16,280394 0,28676 4353,476 16,363562 0,082856 1682,889 16,427116 0,09725 1743,982 16,50071 0,133981 1108,646 16,904119 0,128321 1829,115 17,017418 0,23895 3987,366 17,409172 0,158398 2767,263 17,716999 0,1571 1302,722 17,891594 0,202698 3722,962 18,049681 0,191037 2039,257 18,140236 0,176836 3686,508 18,528196 0,076336 3209,884 19,106394 0,148381 1008, 572 19,118612 0,156251 1000,564 19,173443 0,122128 980,5635 19,335644 0,098819 2663,262 19,367334 0,112794 2718,314 20,023649 0,199337 3556,408 20,041323 0,195353 1134,629 20,063593 0,224531 4098,26 20,300522 0,113124 3152,333 20,347666 0,200969 882,5596 20,470793 0,208903 2825,334 20,889994 0,26629 3385,819 20,93943 0,057322 1425,772 21,519066 0,226397 5000,98 21,655712 0,298068 3775,697 21,755213 0,316991 1046,586 21,850452 0,518151 3405,871 22,747589 0,302407 1235,601 22,763943 0,277557 1194,603 22,997269 0,34528 1265,661 23,013165 0,225846 2642,188 23,017294 0,551478 6171,03 23,838888 0,406385 12'50,653 24,025209 0,261109 2742,267 24,137253 0,135523 1463,693 24,14039 0,158709 1473,664 24,220345 0,206216 1489,686 24,355286 0,409203 1451,684 24,686199 0,240303 3098,376 24,915867 0,332783 1579,718 25,093962 0,214003 3121,259 25,181305 0,33936 3272,276 25,634459 0,407648 3441,958 25,648405 0,344555 3495,801 25,928818 0,283113 3108,66 26,411203 0,355909 3359,75 26,493782 0,341234 3416,324 27,775286 0,346393 2196,686 28,415859 0,219954 2385,565 29,471397 0,2699 2649,791 29,74654 0,131224 2584,214 30,499264 0,32736 1160,556 30,832899 0,269278 1261,477 32,240211 0,415696 1195,543 32,240601 0,406316 1223,53 32,29216 0,268596 1212,024 33,24297 0,403599 1367,633 34,039223 0,467469 1507,75 34,274136 0,432896 1594,746 35,978645 0,326975 1841,202 37,237282 0,110906 2608,186 37,342949 0,6411 1863,833 Table 25:
Sex Age DiagnosisS-creatinineProteinuriaIrn munosuppression ~

M 63 FSGS 95 0.02 _ pS

M 18 FSGS 99 0.05 _ _ CsA

M 63 FSGS 93 0.05 pS

F 49 FSGS 80 0.05 CsA+pS

F 23 FSGS 69 0.54 CsA

F 26 FSGS 16 0,7 CsA

F 56 FSGS 80 0.8 M 62 FSGS 150 1,9 M 26 FSGS 144 4,9 _ F 26 FSGS 150 11.0 CsA+PS

M 69 MGN 128' 0.02 CsA

M 62 MGN 91 0.17 M 23 MGN 150 0.3 M 37 MGN 73 0.33 M 43 MGN 82 0.7 PS

M 48 MGN 100 1.0 CsA+PS

F 68 MGN 150 1.0 F 21 MGN 80 1.0 CsA+PS

M 44 MGN 118 1.0 CsA

M 45 MGN 93 1.3 M 48 MGN 133 2.4 _ M 37 MGN 93 2.6 M 78 MGN 99 3.3 _ M 47 MGN 93 3.5 pS

F 34 MGN 80 3.5 CsA+PS

M 66 MGN 132 3,6 ..

_' M 38 MGN _100 4.0 CsA+PS

M 43 MGN _ 85 5.1 -F 43 MCD 114 0.01 CsA

M 45 MCD + 93 0.01 F 52 MCD + 118 0.01 -M 52 MCD 93 0.01 -F 44 MCD + 80 0.02 CsA

M 39 MCD * 93 0.02 -M 51 MCD 93 0.05 -M 18 MCD 77 0.05 CsA+PS

F 70 MCD * 95 0.08 M 69 MCD 93 0.08 -F 29 MCD + 160 0.1 M 62 MCD + 93 0.1 -M 21 MCD 57 0.12 _ -F 43 MCD 114 0,01 CSA

F 25 MCD 80 1,2 M 52 MCD 93 0.4 ~ pS

F 80 MCD * 145 __ 7.9

Claims (18)

1. Use of the presence of at least one polypeptide marker in a urine sample for the diagnosis of a renal disease, wherein the polypepgide marker is selected from the group of polypeptide markers as shown in tables 1 to 22.

2. The use according to claim 1, wherein the renal disease is chosen from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

3. The use according to claim 1, wherein the renal disease is IgA-nephropathy.

4. The use according to claim 1, wherein diagnosis relates to differential diagnosis.
between at least two diseases chosen from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

5. The use according to any of claims 1 to 4, wherein the polypeptide marker is selected from the group of polypeptide markers as shown in tables 1 to 13.

6. The use according to claim 3, wherein the polypeptide marker is selected from the group of polypeptide markers as shown in tables 11 to 13.

7. A method for the diagnosis of a renal disease, the method comprising:
a) measuring the presence or the absence of a polypeptide marker in a urine sample, wherein the polypeptide marker is selected from the group of polypeptide markers shown in tables 1 to 22, and b) comparing the probability of the presence of this marker in a disease patient to the probability of the presence of this marker in a control patient, wherein c1) if the probability of the presence of this marker in a disease patient is higher than the probability of the presence of this marker in a control patient, the presence of this marker is indicative for a higher probability of having the disease rather than the control condition, or c2) if the probability of the presence of this marker in a disease patient is lower than the probability of the presence of this marker in a control patient, the absence of the marker is indicative for a higher probability of having the disease rather than the control condition.

8. The method according to claim 7, wherein the individual probabilities in step b) are as indicated in the tables.

9. The method according to any of claims 7 to 8, wherein the control represents the healthy condition.

10. The method according to any of claims 7 to 9, wherein the control represents a renal disease, particularly chosen from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

11. The method according to any of claims 7 to 9, wherein the polypeptide marker is selected from the group of polypeptide markers shown in tables 11 to 13.

12. The method according to any of claims 7 to 11, wherein the method comprises detecting a plurality of the polypeptide markers, preferably at least 3, more preferably at least 10, most preferably at least 50 of the polypeptide markers.

13. The method according to any of claims 7 to 12, wherein ELISA, quantitative Western Blot, radio-immuno-assay, surface plasmon resonance, array, gel electrophoresis, capillary electrophoresis, gas phase ion spectrometry, or mass spectrometry is used for detecting the presence of the marker or markers.

14. The method according to any of claims 7 to 13, wherein the polypeptide markers in.
the sample are separated by capillary electrophoresis. before measurement.

15. The method according to claim 14, wherein mass spectrometry is used for detecting the presence of the marker or markers.

16. Use of capillary electrophoresis-mass spectrometry for the diagnosis, particularly differential diagnosis, of a renal disease in vitro.

17. The use according to claim 16, wherein the renal disease is selected from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

18. Use of capillary electrophoresis-mass spectrometry for the differential diagnosis between at least two renal diseases selected from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.