JP5370799B2 - D / P creatinine marker, D / P creatinine determination method and use thereof - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an indirect method of determining D/P creatinine for deciding peritoneal function in a simple and quick manner, that dispenses with blood collection or a plurality of number of recoveries of dialysate drainage. <P>SOLUTION: Dialysate waste obtained from peritoneal dialysis is prepared, at least one protein marker chosen from among a group of prealbumin, haptoglobin, &alpha;-microglobulin, C4, and the total protein contained in the dialysis drain is measured; and D/P creatinine is indirectly determined by using a preliminarily developed correlation formula indicating the relation between D/P creatinine and the marker concentration. Moreover, based on the conventional standard, PET category is indirectly determined from the D/P creatinine which is determined indirectly. <P>COPYRIGHT: (C)2008,JPO&amp;INPIT

Description

  The present invention relates to a marker that serves as an index of D / P creatinine, which is a criterion for determining peritoneal function, an indirect determination method for D / P creatinine, and uses thereof.

  It is known that when peritoneal dialysis, which is a treatment method for renal failure, is performed for a long period of time, the peritoneal function of the patient tends to decrease due to the stimulation. And this causes the peritoneal permeability to increase, resulting in a decrease in dialysis effect and a risk of developing encapsulating peritoneal sclerosis (EPS).

  For this reason, in the field of dialysis medicine, it is necessary to diagnose a decrease in peritoneal function of a dialysis patient at an early stage. Currently, PET (Peritoneal Equilibration Test) is employed as a method for examining peritoneal function (see Non-Patent Document 1). PET is a method for evaluating peritoneal function in four stages (four categories). In this method, a dialysate is generally stored in the peritoneum of a patient, and creatinine concentration and glucose concentration in the dialysate and blood are measured over time. Then, the water removal ability and waste product removal ability of the peritoneum are evaluated from the change of the creatine concentration and the glucose concentration within the dialysis period, and the evaluation results are classified into categories representing the peritoneal function. Variation in creatinine concentration is an indicator of waste removal ability, and variation in glucose concentration is an indicator of water removal ability. Specifically, when the peritoneal function is classified by creatinine fluctuation, the value of “D / P creatinine” is used. This value indicates the ratio between the creatinine concentration (D) of the dialysate (dialysis drainage) and the blood creatinine concentration (P) at an arbitrary time during dialysis treatment. The relationship between the value of D / P creatinine and each category of PET is disclosed, for example, in Non-Patent Document 2, and from the higher D / P creatinine value, that is, the higher permeability, "High" It is classified into four categories of “High Average”, “Low Average”, and “Low”. Therefore, if classification into the above four categories is performed based on the measured D / P creatinine value of the dialysis patient, adjustment of osmotic pressure of dialysate, dialysis frequency, combined use with hemodialysis, Transition to hemodialysis can be determined. Thus, the category classification by PET is used for preventing the complications as described above. The four categories of PET will be described in more detail. “High”, which has a high permeability, has a relatively high waste removal ability, a low water removal ability, and a “High Average”, which has a relatively high permeability. In general, the waste removal ability is normal, the water removal ability is slightly low, and the permeability is slightly low. “Low Average” has a relatively low waste removal ability and the water removal ability is normal, and the permeability is low. “Low” is evaluated as having relatively low waste removal ability and high water removal ability.

However, in order to measure D / P creatinine and classify the PET category as described above, the dialysate is drained several times after the start of dialysis (for example, 0 hours, 2 hours and 4 hours after the start). It is necessary to let Furthermore, blood collection is also essential. For this reason, a patient is restrained in time for the drainage collection | recovery of predetermined time, Furthermore, the pain of blood collection is accompanied. In addition, since it is difficult to collect samples at home, it is essential to go to a hospital, and there is a problem that both patients and doctors are labor intensive. Furthermore, even with the fast PET method, which is a simplified version of the original PET method, the time that the patient is restrained to collect the dialysate is the same, and at least three types of dialysis drainage drained over time and blood Since it is necessary to measure the creatinine concentration for a total of four types, the measurement itself takes time.
Twardowski ZJ, et al. Peritoneal equilibration test. Perit Dial Bull 1987; 7: 138-47. "Understanding basics of peritoneal dialysis", published by Tokyo Medical Company, Akiyasu Yamashita, October 1, 1998

  Therefore, an object of the present invention is to provide a new marker that does not require blood collection or multiple dialysis drainage recovery and can easily determine peritoneal function.

  The marker of the present invention is a marker for D / P creatinine (hereinafter referred to as “D / P creatinine marker”), and is at least one selected from the group consisting of prealbumin, haptoglobin, α1-microglobulin, C4 and total protein. It contains two proteins.

Moreover, the determination method of D / P creatinine of this invention is characterized by including the following (a)-(c) process.
(A) Step of preparing the drainage of peritoneal dialysis of the subject (b) Step of measuring the D / P creatinine marker of the present invention in the drainage (c) The value of D / P creatinine and the D / P creatinine marker The step of calculating D / P creatinine from the measured value of the marker in the step (b) based on a correlation equation showing the relationship with the amount

The PET category determination method of the present invention includes the following steps (A) and (B).
(A) The process of determining D / P creatinine by the D / P creatinine determination method of this invention (B) The process of determining PET category from the determined D / P creatinine

  As a result of intensive studies, the present inventors have found that the content of a group of proteins in peritoneal dialysis drainage varies depending on the peritoneal function (peritoneal permeability) of a peritoneal dialysis patient. That is, in the peritoneal dialysis drainage of the patient with high peritoneal permeability and the peritoneal dialysis drainage of the patient with low peritoneal permeability, prealbumin, haptoglobin, α1-microglobulin, and total protein, Variations in content were observed. As a result of further investigation, it was found that the amount of these proteins in the peritoneal dialysis drainage and D / P creatinine showed a correlation. Therefore, as in the present invention, when these proteins are used as D / P creatinine markers and the amount in the peritoneal dialysis drainage is measured, the D / P creatinine of the peritoneal dialysis patient is indirectly determined based on this result. it can. Further, classification into the PET category can be performed from the determination result. In addition, as described above, conventional PET needs to collect both dialysis drainage and blood as samples, but according to the method of the present invention, it is sufficient to collect dialysis drainage. Can also be reduced. Furthermore, according to the method of the present invention, one type of dialysis drainage is sufficient for the sample used for the examination of peritoneal function. For this reason, it is not necessary to collect the effluent multiple times, and it is only necessary to perform the measurement on one type of dialysis effluent. Therefore, the operation itself is much simpler than conventional PET. In particular, conventional PET is usually performed only once a year due to the complexity of the process and the burden on patients and doctors, but the method of the present invention is frequently performed because it is extremely simple. Is possible. Therefore, if D / P creatinine or PET is determined for the marker of the present invention, the labor of both the patient and the doctor can be reduced and the peritoneal function can be easily tested. Moreover, since it can be implemented with high frequency, the transition of the PET category can be detected at an early stage. Thereby, for example, the transition period of the PET category from “High Average” to “High”, which is regarded as particularly important, can be detected early. For this reason, for example, the present invention is extremely useful in the treatment of renal failure, for example, change of dialysis conditions according to peritoneal symptoms, prevention of peritonitis due to long-term peritoneal dialysis, and the like.

<D / P creatinine marker>
As described above, the D / P creatinine marker of the present invention comprises at least one protein selected from the group consisting of prealbumin, haptoglobin, α1-microglobulin, C4 and total protein.

  All of these proteins are markers indicating that D / P creatinine is relatively high as the concentration in the peritoneal dialysis effluent is relatively high. In other words, the peritoneal permeability is relatively high. It is a marker. Specifically, in the case of dialysis drainage having a relatively high D / P creatinine value (relatively high permeability), the D / P creatinine value is relatively low (permeability is relatively low). Compared with the liquid, for example, the marker concentration in the dialysis drainage is higher. Therefore, as will be described later, by measuring these markers in dialysis drainage, if the concentration or amount thereof is relatively high, it can be determined that D / P creatinine is relatively high and peritoneal permeability is high. A specific determination method will be described later. Among these markers, α1-microglobulin, prealbumin, and total protein are preferable, and α1-microglobulin is particularly preferable because it shows the highest correlation with D / P creatinine.

<D / P creatinine determination method>
Next, the method for determining D / P creatinine of the present invention includes the following steps (a) to (c) as described above.
(A) Step of preparing the drainage of peritoneal dialysis of the subject (b) Step of measuring the D / P creatinine marker of the present invention in the drainage (c) The value of D / P creatinine and the D / P creatinine marker The step of calculating D / P creatinine from the measured value of the marker in the step (b) based on a correlation equation showing the relationship with the amount

  An example of the D / P creatinine determination method of the present invention is shown below, but the present invention is not limited to this.

  First, the dialysate stored in the patient's peritoneum is drained. Although the storage time is not particularly limited, for example, it is preferable to keep the conditions between patients and each analysis constant. As a specific example, for example, a sample obtained by draining dialysate previously stored in the abdominal cavity for 8 to 12 hours is used as an analysis sample.

  Subsequently, the D / P creatinine marker of the present invention is measured (qualitatively or quantitatively) for the obtained analytical sample. In the present invention, any of prealbumin, haptoglobin, α1-microglobulin, C4 and total protein may be measured as the D / P creatinine marker. The method for measuring the marker is not particularly limited, and a conventionally known detection method for measuring protein can be employed. Moreover, since the above-mentioned protein itself is a well-known protein, the conventionally well-known detection method about each protein is also employable, for example. In addition, even if these proteins are known per se, they can be D / P creatinine markers, and D / P creatinine can be indirectly determined by measuring the amount and concentration in peritoneal dialysis effluent. The present inventors have found for the first time.

  Specific examples of the detection method include an enzyme method, an immunological method, and an electrophoresis method. Examples of the immunological technique include conventionally known methods using antigen-antibody reaction. For example, immunoturbidimetric methods such as ELISA (Enzyme-Linked Immuno Sorbent Assay), Western blotting, and latex agglutination turbidimetry. Gold colloid aggregation method, immunocompatibility method (neferometry method) and the like can be employed. The antibody used in this method may be, for example, a commercially available antibody, or a monoclonal antibody or a polyclonal antibody prepared in-house.

  The marker measurement by the immunological technique can be detected more easily by a test tool using a conventionally known technique. Examples of the inspection tool for measuring the D / P creatinine marker by the ELISA method include a test piece in which a reagent for the marker is arranged on a substrate having a porous structure or a capillary structure. Examples of the reagent include an antibody against a D / P creatinine marker and an antigen (marker). In the case of a test piece in which an anti-D / P creatinine antibody is immobilized as the reagent, first, peritoneal dialysis effluent is dropped, and the immobilized antibody and the antigen (D / P creatinine marker) in the peritoneal dialysis effluent The antigen reaction is performed. Further, a labeled anti-D / P creatinine antibody is added, and an antigen-antibody reaction with the D / P creatinine marker bound to the immobilized antibody is performed. And the D / P creatinine marker in the said waste liquid can be measured by detecting the label | marker of the labeled antibody couple | bonded with the said D / P creatinine marker. In addition, a peritoneal dialysis drainage containing a D / P creatinine marker and a labeled D / P creatinine marker are added to a test piece on which an anti-D / P creatinine antibody is immobilized, and labeled with an unlabeled marker. A marker may be competitively bound to the antibody. In this case, the antigen D / P creatinine marker in the drainage can be measured by detecting the label of the labeled marker bound to the immobilized antibody.

  The substrate is not limited and is preferably a material (for example, a material excellent in water absorption) or a structure capable of carrying (for example, immobilizing) the reagent and developing peritoneal drainage. Examples of the substrate include filter paper, chromatography paper, and non-woven fabric. In addition, a polymer porous body can be mentioned. The material of the porous body is not limited, and examples thereof include cellulose polymers such as cellulose, cellulose acetate, nitrocellulose, polyethylene, polypropylene, polyamide resins (for example, nylon), polyester, acrylonitrile resin, Examples thereof include resins such as tetrafluoroethylene. Moreover, when using a test piece, a conventionally well-known method can be suitably employ | adopted, for example in order to improve a measurement sensitivity, measurement accuracy, and a series of operativity.

  Examples of the electrophoresis method include one-dimensional electrophoresis and two-dimensional electrophoresis. According to these methods, for example, all markers can be separated by one electrophoresis (one-dimensional and two-dimensional electrophoresis). For this reason, all the markers can be measured at once from the presence or absence of marker spots in the gel after electrophoresis and the density of the spots. It is preferable that the conditions for electrophoresis, the total protein amount of the sample to be subjected to electrophoresis, and the like be constant between samples. The staining method is not particularly limited, and examples thereof include fluorescent staining such as silver staining, Coomassie brilliant blue (CBB) staining, and SYPRO Ruby staining (trade name).

  Prealbumin, haptoglobin, α1-microglobulin, C4 and total protein are known proteins as described above, and each is known as a blood biochemical test item. Therefore, you may measure the density | concentration and quantity in peritoneal dialysis drainage using a well-known measuring method. Examples of prealbumin measurement methods include turbidimetry, haptoglobin and C4 measurement methods such as immunoturbidimetry, and α1-microglobulin measurement methods such as latex agglutination immunization and total protein As a measuring method, for example, a burette method is common.

  Then, for example, D / P creatinine may be indirectly calculated from the measured value based on a correlation equation indicating a correlation between the D / P creatinine marker and D / P creatinine. Hereinafter, D / P creatinine calculated indirectly according to the present invention is referred to as “estimated D / P creatinine”, and D / P creatinine calculated directly from blood concentration and dialysis drainage concentration by a conventional method is “True D / P creatinine”. For example, this correlation formula is used to measure the true D / P creatinine of a plurality of dialysis patients in advance by the conventional method, while measuring the D / P creatinine marker in the peritoneal dialysis drainage of the same dialysis patients. It can be created by analyzing the measurement results. Then, the estimated D / P creatinine can be indirectly determined by substituting the measured value of the D / P creatinine marker in the dialysis drainage of the subject into this correlation equation. In preparing the correlation equation, the sampling time of the dialysis drainage used for the measurement of true D / P creatinine (dialysate storage time) is not particularly limited, but is unified among a plurality of dialysis drainages to be measured. For example, 2 to 4 hours, preferably 4 hours. On the other hand, the dialysis drainage collection time (dialysis fluid storage time) for measuring the D / P creatinine marker (to calculate the estimated D / P creatinine) is not particularly limited. Yes, preferably 8-12 hours, more preferably 8 hours. It is also preferable that the dialysis drainage collection time of the subject is the same.

  As a specific example, the correlation between true D / P creatinine measured using peritoneal dialysis drainage and blood collected after 4 hours storage and the D / P creatinine marker of the present invention is shown below. Note that the present invention is not limited to these correlation equations.

  As described above, when peritoneal dialysis is continued, the peritoneal function decreases, so D / P creatinine increases, and the above PET category shifts to “High”. It has been reported that patients who have reached the “High” category have a high risk of developing peritonitis or sclerosing capsular peritonitis, for example. In order to prevent the onset of such peritonitis, in peritoneal dialysis treatment, it is necessary to examine, for example, peritoneal rest period, dialysis stop time, combined use with hemodialysis, or shift to hemodialysis. Generally, it is known that when the PET category is “High Average” before “High”, it is in the best condition and good peritoneal dialysis can be performed. Therefore, it is possible to detect the transition period from the “High Average” to the “High”, and in particular, to detect the increase behavior within the numerical range of D / P creatinine classified as “High Average”. It is very important to do. However, conventional PET requires blood collection and dialysis fluid collection multiple times with a set collection time, as described above, and is accompanied by patient pain and a great deal of labor by the patient and doctor. Measurement could not be performed. However, according to the present invention, blood collection is unnecessary, and the peritoneal dialysis drainage need only be collected once. For this reason, it is possible to collect samples frequently and regularly, and it is not limited to collecting samples at hospitals, and it is only necessary to mail samples collected at home to hospitals and laboratories. Both doctors' work can be reduced. It is also possible for the patient himself / herself to measure the marker of the present invention at home using a measurement kit, a simple measurement device, or the like and confirm the estimated D / P creatinine.

<Determination method of PET category>
Subsequently, the PET category determination method of the present invention includes the following steps (A) and (B) as described above.
(A) The process of determining D / P creatinine by the D / P creatinine determination method of this invention (B) The process of determining PET category from the determined D / P creatinine

  PET used in the examination of peritoneal function is classified into four categories according to the numerical range of D / P creatinine. And as above-mentioned, the D / P creatinine marker of this invention in peritoneal dialysis drainage shows a correlation with D / P creatinine. Therefore, if the estimated D / P creatinine is obtained indirectly by measuring the D / P creatinine marker as described above, the classification into the PET category can be performed indirectly based on this result.

  The correlation equation as described above can be used to determine the estimated D / P creatinine. In creating this correlation formula, for example, when a sample drained in 4 hours from the start of dialysis is used for the measurement of true D / P creatinine, the estimated D / D of drainage 4 hours after dialysis is calculated from the correlation formula. P creatinine can be calculated. In this case, for example, if the estimated D / P creatinine is in the range of about 0.81-1.03, “High”, and if the estimated D / P creatinine is in the range of about 0.65-0.81, “High Average” is set. ”,“ Low Average ”if the estimated D / P creatinine is in the range of about 0.5 to 0.65,“ Low ”if the estimated D / P creatinine is in the range of about 0.34 to 0.5, Each can be classified. Note that it is not necessary to strictly determine which category the estimated D / P creatinine value is, for example, a boundary value of each category. For example, even if the value belongs to “High Average”, it can be determined that the risk of becoming “High” or the possibility of “High” is higher as the upper limit value is approached. Therefore, for example, when the estimated D / P creatinine is 0.81, it may be determined as “High”, or may be determined as “High Average” with a very high risk of high. These are merely examples, and the present invention is not limited thereto.

  Further, as a method of indirectly determining the PET category by detecting the D / P creatinine marker of the present invention, as described above, in addition to the method of indirectly determining the estimated D / P creatinine, for example, the following: Such a method is given. In addition, this invention is not restrict | limited at all to these forms.

(First form)
Electrophoresis (for example, primary or secondary) is performed on the dialysis drainage of the subject, the gel after electrophoresis is stained, and the spot of the D / P creatinine marker on the stained electrophoresis gel is confirmed. Here, the relatively darker the spot of the D / P creatinine marker of the present invention, the higher the permeation ability, that is, the patient whose D / P creatinine is relatively high and the category is relatively higher than “High”. I can judge.

(Second form)
As an evaluation criterion, electrophoresis (for example, primary or secondary) and electrophoresis gel are stained for dialysis drainage of a dialysis patient whose PET category is known in advance. This electrophoretic image is used as an evaluation standard. As evaluation criteria, the drainage of four PET category patients may be used, respectively, or the drainage of patients of the PET category to be classified may be used. Specific examples include a “High” category and a “High Average” category, a “High” category and a “Low” category, a “Low Average” category, and the like. On the other hand, the dialysis waste liquid of the subject is subjected to electrophoresis and gel staining under the same conditions. Subsequently, the electrophoretic image of the evaluation reference and the electrophoretic image of the subject are collated, and the presence / absence of the spot of the D / P creatinine marker or the density of the staining of the spot is compared. Then, the evaluation criteria category in which the D / P creatinine marker exhibits the same behavior can be evaluated as the PET category of the subject.

(Third form)
As an evaluation standard, the content ratio of each marker per a certain amount of total protein is measured for a dialysis drainage of a dialysis patient whose PET category is known. The content ratio of each marker in each category is used as an evaluation standard. As evaluation criteria, the drainage of four PET category patients may be used, respectively, or the drainage of patients of the PET category to be classified may be used. Specific examples include a “High” category and a “High Average” category, a “High” category and a “Low” category, a “Low Average” category, and the like. On the other hand, the dialysis drainage of the subject is measured in the same manner, and the content ratio of each marker per fixed amount of total protein is measured. Then, by comparing the content ratio of each marker of the subject with the content ratio of the evaluation standard, the category of the evaluation standard that shows the same content ratio can be evaluated as the category of the test object. This method is suitable when adopting prealbumin, haptoglobin, α1-microglobulin, or C4 as the D / P creatinine marker.

(4th form)
As an evaluation criterion, the concentration of the D / P creatinine marker is measured in advance on the dialysis drainage of a dialysis patient whose PET category is known. As evaluation criteria, the drainage of four PET category patients may be used, respectively, or the drainage of patients of the PET category to be classified may be used. Specific examples include a “High” category and a “High Average” category, a “High” category and a “Low” category, a “Low Average” category, and the like. On the other hand, the concentration of the D / P creatinine marker is measured in the same manner for the dialysis drainage of the subject. The method for measuring the D / P creatinine marker concentration is not particularly limited, and conventionally known protein detection methods such as a method using an antigen-antibody reaction with an anti-marker antibody and a method using HPLC can be used. Then, by comparing the measured marker concentration of the detection target with the evaluation criterion, it is possible to evaluate that the category of the evaluation criterion showing the same level of concentration belongs to the category of the subject.

  In addition, using commercially available computers, based on the correlation between estimated D / P creatinine and true D / P creatinine and the correlation between estimated D / P creatinine and PET category, estimated D / P creatinine, PET It is also possible to determine the category or peritoneal function and to determine the future dialysis schedule. Specifically, the estimated D / P creatinine is calculated from the measured value of the D / P creatinine marker relating to the dialysis drainage of the subject based on the above-described correlation equation, and the obtained estimated D / P creatinine is calculated according to the PET category. It is possible to employ a system for determining the PET category by comparing with the existing reference value of true D / P creatinine for determining the PET. A data processing apparatus in which a program for executing these series of steps is previously incorporated in a computer, a computer-readable recording medium storing the program, or the like can be used. In addition, as a general index for evaluating the peritoneal function of a patient, there are each solute concentration and water removal amount. From these data, a pile-popovich model known as a macroscopic pharmacokinetic model of peritoneal dialysis is used. A method for examining peritoneal functions such as elution removal ability, water removal ability, etc. is known. Therefore, a more detailed evaluation of peritoneal function is possible by combining this method for testing peritoneal function and the method according to the present invention.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

  The presence / absence of a correlation between the D / P creatinine marker of the present invention and the true D / P creatinine according to the conventional method was confirmed.

  For 33 patients, using the peritoneal dialysis fluid stored for 4 hours as the first measurement, measurement of true D / P creatinine by the conventional method and various D / P creatinine marker concentrations by the method described later Measurements were made. Furthermore, for the 13 patients out of the 33 patients described above, as the second measurement, after 6 to 12 months from the first measurement, again the measurement of true D / P creatinine and various D / P P creatinine marker concentration was measured. Further, for the three patients out of the 13 patients described above, as the third measurement, the measurement of true D / P creatinine was carried out in the same manner 6 to 12 months after the second measurement, and various measurements were made. The D / P creatinine marker concentration was measured. Further, for one patient among the three patients, as the fourth measurement, 6 to 12 months after the third measurement, the true D / P creatinine measurement, The D / P creatinine marker concentration was measured. The measurement of the D / P creatinine marker concentration is performed on the patient by storing the dialysate in the abdominal cavity for 8 to 12 hours and then draining the peritoneal dialysis drainage as a sample by the following method. It was.

(Measurement of prealbumin concentration)
About 30 microliters of samples, prealbumin was measured by the immuno-ratio method (nepherometry method) using N-antiserum prealbumin (Dade Behring Co., Ltd.).
(Measurement of haptoglobin concentration)
About 30 μL of the sample, haptoglobin was measured by an immuno-ratio method (nepherometry method) using N-antiserum haptoglobin (Dade Behring Co., Ltd.).
(Measurement of α1-microglobulin concentration)
With respect to 8 μL of the sample, α1-microglobulin was measured by an immunoturbidimetric method (latex aggregation immunoturbidimetric method) using LX reagent Eiken α1-M-III (trade name, Eiken Chemical Co., Ltd.).
(Measurement of C4 concentration)
About 5 μL of the sample, C4 was measured by an immunoturbidimetric method (latex agglutination immunoturbidimetric method) using N-assay TIA C4-SH Nittobo (trade name, Nittobo Co., Ltd.).
(Measurement of total protein concentration)
For 350 μL of the sample, the total protein was measured by the burette method.

  A correlation equation showing the correlation between the true D / P creatinine and each marker was determined from the results of the total 50 true D / P creatinines and the results of the respective marker concentrations. These results are shown in the table below. As shown in the table below, true D / P creatinine and each marker in the peritoneal dialysis fluid stored for 4 hours showed a correlation. Among them, α1-microglobulin showed a very high correlation with true D / P creatinine. From the above results, D / P creatinine can be estimated indirectly by measuring the D / P creatinine marker in the peritoneal dialysis drainage, and the PET category can be further indirectly determined based on the estimated D / P creatinine. It became clear that. When 33 patients were classified into categories using conventional PET, at the time of the first measurement, there were 5 High, 16 High Average, 9 Low Average, and 3 Low. At the time of the second measurement, 13 people were high 4 people, high average 6 people, low average 2 people, and low 1 people. From this, it can be said that the above-mentioned correlation is reliable in the range of all categories from Low to High.

  In Example 1, among the 13 patients who performed the second measurement 6 to 12 months after the first measurement, five patients were determined from true D / P creatinine. The PET category changed. Therefore, for each of these patients, it was confirmed whether or not the α1-microglobulin concentration was changed with the change of true D / P creatinine.

  Based on the measurement results of Example 1, the relationship between the change in true D / P creatinine and the change in the α1-microglobulin (α1M) concentration of the patient is shown in the graph of FIG. Show. FIG. 6A shows the result of shifting the PET category from High Average to High, and FIG. 6B shows the result of moving the PET category from High to High Average. In both figures, the arrow indicates the category transition direction for the same patient, and the bold line in the graph indicates the D / P creatinine value indicating the boundary between High and High Average and the boundary between High Average and Low Average from the top. It is.

  As shown in the figure, the α1-microglobulin concentration increases with an increase in the true D / P creatinine, which is the basis for classification of the PET category, and the α1-microglobulin with a decrease in the true D / P creatinine. It was confirmed that the concentration decreased.

(Reference Example 1)
The presence or absence of a correlation between α1-microglobulin in drainage and residual kidney function was confirmed.

(1) Correlation with residual kidney function The α1-microglobulin concentration in the drainage was measured in the same manner as in Example 2 for 14 patients with residual kidney function (urine volume 100 mL or more). The same patient's creatinine clearance (how much liquid is filtered per minute by the kidney) was examined by a conventional method. The correlation between the α1-microglobulin concentration in the drainage and the urine volume of the patient and the correlation between the α1-microglobulin concentration in the drainage and the creatinine clearance were confirmed. As a result, the α1-microglobulin concentration in the effluent showed no correlation with either urine volume or creatinine clearance. In other words, the α1-microglobulin concentration in the drainage was not correlated with the residual kidney function of the patient.

(2) Correlation between α1-microglobulin and D / P creatinine of patients with residual kidney function A drainage sample collected in the same manner as in Example 2 was obtained from patients with residual kidney function (urine volume 100 mL or more: 36 No.) sample group and a sample group of patients (less than 100 mL of urine volume: 14) with no residual kidney function, and the α1-microglobulin concentration in each sample was measured. Moreover, about these patients, D / P creatinine was measured by the conventional method like the said Example 2. And the correlation of (alpha) 1-microglobulin and D / P creatinine was confirmed about each of the patient with a residual kidney function and the patient without a residual kidney function. As a result, as shown below, a correlation was confirmed between α1-microglobulin and D / P creatinine regardless of the presence or absence of residual kidney function.

  As shown in (1) above, there is no correlation between α1-microglobulin in the drainage and residual kidney function, and as shown in (2), α1-microglobulin in the drainage. Had a correlation with D / P creatinine, which is the basis for the PET category, regardless of the presence or absence of residual kidney function. Therefore, according to the analysis method using α1-microglobulin in dialysis drainage as a marker, D / P creatinine and PET categories of all peritoneal dialysis patients are predicted without being affected by the presence or absence of the patient's residual kidney function. It is possible.

  Thus, if the amount of the marker of the present invention in the peritoneal dialysis drainage is measured, the D / P creatinine of the patient can be indirectly determined, and further, the determination result can be classified into the PET category. Further, unlike conventional PET, it is only necessary to collect the dialysis drainage, so that the patient's pain can be reduced and the examination is simplified. In particular, conventional PET is usually performed only once a year due to the complexity of the process and the burden on patients and doctors. However, the method of the present invention is very simple because it is extremely simple. Can be done at a frequency. Therefore, if the D / P creatinine and PET determination method of the present invention is used for the marker of the present invention, the labor of both the patient and the doctor can be reduced and the peritoneal function test can be easily performed. In particular, since the transition period of the PET category from “High Average” to “High” can be detected at an early stage, it is extremely useful, for example, in preventing the onset of peritonitis due to long-term peritoneal dialysis by changing the treatment method.

FIG. 1 is a graph showing the correlation between true D / P creatinine change and α1-microglobulin change in the same patient in Example 1 of the present invention, and (A) shows a change from High Average to High. The result of the patient whose category was changed, and (B) is the result of the patient whose category was changed from High to High Average.

Claims (8)

A method for determining D / P creatinine, comprising:
A D / P creatinine determination method comprising the following steps (a) to (c):
(A) preparing a drainage of peritoneal dialysis of a subject (b) a concentration of at least one marker selected from the group consisting of prealbumin, haptoglobin, α1-microglobulin, C4 and total protein in the drainage (C) Correlation equation showing the relationship between the value of D / P creatinine directly calculated from the blood concentration and the concentration in the drainage of peritoneal dialysis and the concentration of the marker in the drainage of the peritoneal dialysis based on the (b) from the concentration of the markers Oite measured step, a step of indirectly calculating the D / P creatinine of the subject The correlation equation is the value of D / P creatinine plurality of dialysis patients, a correlation equation created from the measured value of said plurality of dialysis patients D / P creatinine marker of claim 1, wherein D / P Creatinine determination method. The D / P creatinine determination method according to claim 2 , wherein the D / P creatinine values of the plurality of dialysis patients are values for drainage of 2 to 4 hours after the start of peritoneal dialysis. The D / P creatinine determination method according to claim 2 or 3 , wherein the measured value of the D / P creatinine marker of the plurality of dialysis patients is a value in drainage of 8 to 12 hours after the start of peritoneal dialysis. The method for determining D / P creatinine according to any one of claims 1 to 4, wherein in the step (a), the drainage of peritoneal dialysis of the subject is drainage for 8 to 12 hours after the start of peritoneal dialysis. . The D / P creatinine determination method according to any one of claims 1 to 5, wherein the marker measurement method is a method using at least one of an immunological method and an electrophoresis method. A PET category determination method,
A PET category determination method comprising the following steps (A) and (B):
(A) The process of determining D / P creatinine by the D / P creatinine determination method as described in any one of Claims 1 to 6 (B) The process of determining a PET category from the determined D / P creatinine The PET category determination method according to claim 7, wherein the High Average category and the High category are determined.

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