CN117310179A - Application of substance for detecting fat factor Ism1 level in preparation of reagent for evaluating renal function of subject - Google Patents

Application of substance for detecting fat factor Ism1 level in preparation of reagent for evaluating renal function of subject Download PDF

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CN117310179A
CN117310179A CN202311202087.6A CN202311202087A CN117310179A CN 117310179 A CN117310179 A CN 117310179A CN 202311202087 A CN202311202087 A CN 202311202087A CN 117310179 A CN117310179 A CN 117310179A
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ism1
level
renal function
serum
filtration rate
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刘金波
王川
徐明月
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Qilu Hospital of Shandong University
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    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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Abstract

The present disclosure provides for the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing renal function in a subject. The disclosure also provides the use of a substance that detects the level of fat factor Ism1 in the preparation of a reagent for assessing glomerular filtration rate and the use of a substance that detects the level of fat factor Ism1 in the preparation of a reagent for predicting risk of progression of renal function. According to the present disclosure, renal function can be assessed by Ism1 levels, glomerular filtration rate can be assessed by Ism1 levels, and risk of progression of renal function can be predicted by Ism1 levels.

Description

Application of substance for detecting fat factor Ism1 level in preparation of reagent for evaluating renal function of subject
Technical Field
The disclosure relates to the technical field of biological medicine, in particular to application of a substance for detecting the level of a fat factor Ism1 in preparation of a reagent for evaluating renal function of a subject.
Background
Kidneys are one of the important organs of the human body, and their main functions include filtering blood, removing waste, regulating water electrolyte balance, maintaining acid-base balance, producing urine, etc. The kidney weighs only about 0.5% of body weight, but the amount of blood flowing into the kidney is 20% to 25% of total cardiac output, and the blood contains a variety of substances having nephrotoxicity, so the kidney is one of the weakest organs. For example, when an excessive amount of drugs is injected into the body, or metabolic diseases such as diabetes, hypertension, etc. occur, the renal function may be gradually impaired, eventually leading to renal failure. The progression of kidney disease can be divided into 5 stages, stage 1: glomerular hypertrophy and ultrafiltration generally have no apparent symptoms. Stage 2: the structural change is accompanied by normal albumin excretion (normal albuminuria). Stage 3: the most typical sign of this stage is persistent microalbuminuria. Stage 4: overt diabetic nephropathy, a stage characterized by persistent proteinuria and usually accompanied by retinopathy or other kidney disease, has normal or slightly elevated serum creatinine concentrations. Stage 5: end-stage chronic kidney disease characterized by a significant decrease in glomerular filtration rate, arterial hypertension, low serum renin, reduced protein excretion, and progressive renal insufficiency. Diabetes and drug-induced nephropathy are the most common conditions in clinic, and particularly with changes in dietary structure and lifestyle, the number of diabetics rises year by year, and the prevalence of diabetes in people 18 years and older in china is about 12.8%, i.e. about 1/8 of adults have diabetes. Adipose tissue is a major metabolic and energy storage tissue that plays an important role in many metabolic pathways. Adipose tissue can monitor and regulate systemic homeostasis by producing and releasing potent proteins into the circulation, known as adipokines. Fat factors act as endogenous signal molecules on adipose tissues and energy metabolism organs, and control the functional homeostasis of the metabolic activities of the organism. Fat factors play an important role in diabetes, kidney disease, and the like.
Currently, the main indicators for kidney function assessment include glomerular filtration rate and albuminuria. Albuminuria is an important index for renal function assessment, but albuminuria has many limitations in use for renal function assessment, such as low specificity (albuminuria may be caused by exercise, diet, posture, infection, other kidney diseases, etc.), high fluctuation (is greatly affected by diet and water intake, medicines, etc.), poor sensitivity, and albuminuria is not suitable for assessment of renal function in all stages. Currently, glomerular filtration rate is a well-known index reflecting renal function.
However, glomerular filtration rate cannot be obtained by direct detection, and renal function is often assessed clinically by detecting urine or plasma clearance (e.g., inulin clearance) of exogenous markers, or by detecting Serum creatinine (Scr) levels or cystatin C levels. The method for detecting the urine or plasma clearance of the exogenous marker has the advantages of higher cost, complicated detection steps, radionuclide is needed, and the application range is limited; by the method for detecting serum creatinine level or cystatin C level, more influencing factors such as muscle content, diet and the like can influence the detection result of serum creatinine when detecting serum creatinine, so that the accuracy of the serum creatinine for evaluating renal function is poor; however, cystatin C has no unified detection standard at present, so that the application of cystatin C in the evaluation of renal functions is limited. Accordingly, there is a need to provide a method or application that can evaluate kidney function that is convenient to detect.
Disclosure of Invention
The present disclosure has been made in view of the above-mentioned state of the art, and an object thereof is to provide a use of a substance for detecting the level of a fat factor Ism1 in the preparation of a reagent for evaluating renal function of a subject.
To this end, a first aspect of the present disclosure provides the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing renal function in a subject.
In the present disclosure, the relationship between the level of the fat factor Ism1 and the renal function was studied, and the renal function of a diabetic patient can be evaluated by detecting the level of the fat factor Ism 1. Thus, it is possible to provide the use of a substance for detecting the level of the fat factor Ism1 in the preparation of a reagent for evaluating renal function.
In an application to which the first aspect of the present disclosure relates, optionally, the glomerular filtration rate, and hence the renal function of the subject, is assessed by detecting the level of the fat factor Ism 1. Thus, the glomerular filtration rate can be evaluated by detecting the level of the fat factor Ism1, and further the renal function can be evaluated by the glomerular filtration rate.
In an application to which the first aspect of the present disclosure relates, optionally, the subject is a renal patient. Thus, renal function of a patient suffering from renal disease can be evaluated.
In an application to which the first aspect of the present disclosure relates, optionally, the subject is a diabetic nephropathy patient. Thus, the renal function of a diabetic nephropathy patient can be evaluated.
In the application to which the first aspect of the present disclosure relates, optionally, the level of the fat factor Ism1 is inversely related to glomerular filtration rate.
In the application to which the first aspect of the present disclosure relates, optionally, the substance is for detecting the level of the adipokine Ism1 in the serum of the subject. Thus, the renal function of the subject can be assessed by detecting the level of the fat factor Ism1 in the serum.
In the application to which the first aspect of the present disclosure relates, optionally, the level of said fat factor Ism1 in serum is detected by enzyme-linked immunosorbent assay. The detection principle of enzyme-linked immunosorbent assay (ELISA) is that a protein to be detected is combined with an enzyme-labeled antigen or an enzyme-labeled antibody, and then a reaction substrate is added, so that the substrate is catalyzed by enzyme and a colored product is produced, and further qualitative or quantitative analysis is carried out according to the depth of the color reaction. Since the antigen-antibody binding sensitivity is high and the catalytic frequency of the enzyme is high, the enzyme-linked immunosorbent assay is used to detect the Ism1 level with high sensitivity.
A second aspect of the present disclosure provides the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing glomerular filtration rate. Thus, the glomerular filtration rate can be evaluated by detecting the level of the fat factor Ism1, thereby facilitating the subsequent use of the glomerular filtration rate to evaluate renal function in diabetics.
A third aspect of the present disclosure provides the use of a substance that detects the level of the fat factor Ism1 in the preparation of an agent that predicts the risk of progression of renal function. Thus, the risk of progression of renal function can be predicted by detecting the level of the fat factor Ism1, and thus, the therapeutic strategy can be adjusted with ease and the management of the disease can be facilitated.
In the application to which the third aspect of the present disclosure relates, optionally, the level of the fat factor Ism1 is greater than 1.249ng/mL, there is a high risk of renal function progression. Thus, when the level of Ism1 is greater than 1.249ng/mL, a high risk of renal function progression can be assessed.
According to the present disclosure, it is possible to provide a use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing renal function in a subject.
Drawings
FIG. 1 is a graph showing serum Ism1 level results for groups G1-2 and G3-5 according to examples of the present disclosure.
Fig. 2 is a graph showing serum Ism1 level results for groups G1, G2, G3, and G4-5 according to the examples of the present disclosure.
Fig. 3 is a graph showing the results of a linear fit of serum Ism1 levels to glomerular filtration rate in accordance with embodiments of the present disclosure.
Fig. 4 is a ROC graph illustrating Ism1 evaluation of glomerular filtration rate according to embodiments of the present disclosure.
Fig. 5 is a ROC graph illustrating Ism1 prediction of renal function progression-related endpoint events according to embodiments of the present disclosure.
FIG. 6 is a schematic diagram showing the results of Kaplan-Meier analyses of the group with Ism1<1.249ng/mL and the group with Ism 1. Gtoreq.1.249 ng/mL according to the examples of the present disclosure.
Detailed Description
Embodiments of the present disclosure are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by way of the drawings are exemplary only and are not to be construed as limiting the present disclosure.
It will be understood by those skilled in the art that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.
It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the prior art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
In order to facilitate an understanding of the present disclosure, the present disclosure is further illustrated by way of example in the accompanying drawings, and the specific examples are not to be construed as limiting the embodiments of the present disclosure. Those skilled in the art will appreciate that the drawings are merely schematic representations of the embodiments, and that the components in the drawings are not necessarily required to practice the present disclosure.
The present disclosure relates to the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing renal function in a subject.
In the present disclosure, the relationship of the fat factor Ism1 level to the kidney function was studied, whereby the kidney function can be evaluated by detecting the fat factor Ism1 level.
In the present disclosure, ism1 is an insulin-like adipokine, which may also be referred to as Ism1, ism-1, isthmin 1 or Isthmin-1.
In the present disclosure, the subject may be a renal patient. In some examples, the kidney disease may be selected from, but is not limited to, nephrotic syndrome, kidney cancer, chronic kidney failure, diabetic nephropathy, diabetic kidney failure, acute pyelonephritis, acute kidney failure, hypertensive kidney disease, rayleigh syndrome, gout, sjogren's syndrome, behcet's disease, lupus, candidiasis, nephrotic hemorrhagic fever, leptospirosis, legionella disease, autosomal dominant hereditary polycystic kidney disease, and hydronephrosis.
In the present disclosure, the subject may be a diabetic patient. In some examples, a diabetic patient may refer to a type II diabetes (or type 2 diabetes) patient. In some examples, the subject may be a diabetic nephropathy patient.
In some examples, the subject may be a diabetic nephropathy patient. Thus, it is possible to provide the use of a substance for detecting the level of the fat factor Ism1 in the preparation of a reagent for evaluating renal function in a diabetic nephropathy patient.
In some examples, the level of Ism1 may be correlated with renal function. In some examples, the level of Ism1 may be correlated to renal function in a diabetic patient.
In some examples, renal function may be related to glomerular filtration rate. In some examples, renal function in a diabetic patient may be related to glomerular filtration rate.
In the present disclosure, glomerular filtration rate (glomerular filtration rate, GFR), which may also be referred to as evfr, refers to the amount of two nephrogenic filtrates per unit time.
In some examples, renal function in a diabetic patient can be assessed by glomerular filtration rate.
In some examples, kidney function may be divided into five phases, a first phase of kidney function, a second phase of kidney function, a third phase of kidney function, a fourth phase of kidney function, and a fifth phase of kidney function, respectively. Wherein, the kidney function in the first stage of kidney function is normal, and trace amount of proteinuria can be detected; the second stage of renal function is mild renal failure; the third phase of kidney function is moderate kidney failure; the fourth stage of renal function is severe renal failure; the fifth phase of renal function is end-stage renal failure.
In some examples, glomerular filtration rate is greater than or equal to 90mL/min/1.73m 2 And is associated with the first phase of renal function. In some examples, 60mL/min/1.73m 2 Glomerular filtration rate less than or equal to 90mL/min/1.73m 2 And is associated with the second phase of renal function. In some examples, 30mL/min/1.73m 2 Glomerular filtration rate less than or equal to 60mL/min/1.73m 2 And, in turn, is associated with phase III renal function. In some examples, 15mL/min/1.73m 2 Glomerular filtration rate less than or equal to 30mL/min/1.73m 2 And, in turn, is associated with stage IV renal function. In some examples, glomerular filtration rate is < 15mL/min/1.73m 2 And is associated with the fifth phase of renal function.
In some examples, renal function in a diabetic patient can be assessed by detecting the level of Ism 1.
In some examples, the level of Ism1 in blood may be detected. In some examples, the level of Ism1 in serum may be detected. Thus, the renal function can be evaluated by collecting a blood or serum sample and detecting the blood or serum sample to obtain the level of Ism 1.
In some examples, the level of the adipokine Ism1 can be detected by immunoassay, protein electrophoresis, mass spectrometry, protein chip technology, or fluorescent co-precipitation. Thus, the level of Ism1 can be detected.
Wherein an immunoassay can utilize specific antibodies to bind to a protein of interest and then determine protein levels by specific optical, chemical or radioactive signaling of the substrate; protein electrophoresis can be performed by separating proteins in a blood sample into distinct bands, and then determining the level of a particular protein based on the charge and size of the protein; the mass spectrometry can be used for analyzing ions according to mass-to-charge ratios through a mass spectrometer after ionization of a sample, so that information such as the mass and the relative abundance of proteins in the sample can be obtained; protein chip technology can detect protein levels by binding proteins in a sample to specific probes on a chip; the fluorescence co-precipitation method can use a fluorescence-labeled antibody to measure protein levels by binding to the target protein and then by fluorescence signaling.
In some examples, immunoassays may include enzyme-linked immunosorbent assays (ELISA), radioimmunoassays (RIA), and immunofluorescence. Thus, the level of Ism1 can be detected by an enzyme-linked immunosorbent assay or a radioimmunoassay.
In some examples, protein electrophoresis may include polyacrylamide gel electrophoresis (PAGE) and gel filtration chromatography electrophoresis (GFE). Thus, the level of Ism1 can be detected by polyacrylamide gel electrophoresis or gel filtration chromatography.
In some examples, mass spectrometry may include mass spectrometry (MALDI-TOF) and liquid chromatography mass spectrometry (LC-MS). Thus, the level of Ism1 can be detected by mass spectrometry or liquid chromatography mass spectrometry.
In some examples, preferably, the level of Ism1 may be detected by enzyme-linked immunosorbent assay. The basic principle of enzyme-linked immunosorbent assay is that antigen or antibody is combined on the surface of a solid carrier and keeps the immunological activity, when in measurement, the protein to be measured and the enzyme-labeled antigen or antibody react with the antigen or antibody on the surface of the solid carrier, the antigen-antibody complex formed on the solid carrier is separated from other substances by a washing method, finally the enzyme amount combined on the solid carrier is in a certain proportion with the amount of detected substances in a sample, after the substrate of enzyme reaction is added, the substrate is catalyzed by the enzyme to become a colored product, and the amount of the product is directly related with the amount of the detected substances in the sample, so that the quantitative or qualitative analysis can be performed according to the darkness of the color reaction, and the effect of the reaction can be greatly amplified due to higher sensitivity of antigen-antibody combination and higher catalytic frequency of the enzyme, so that the enzyme-linked immunosorbent assay is used for detecting the level of Ism1 with higher sensitivity.
In some examples, the level of Ism1 can be detected using an Ism1 protein detection kit. This can facilitate detection of the level of Ism 1.
In some examples, the level of Ism1 may have a correlation with glomerular filtration rate. In the present disclosure, a study on the relationship between the level of Ism1 and glomerular filtration rate showed that the level of Ism1 has a correlation with glomerular filtration rate.
In some examples, glomerular filtration rate, and thus renal function, can be assessed by detecting the level of Ism 1. Thus, the glomerular filtration rate can be evaluated by detecting the level of the fat factor Ism1, and further the renal function can be evaluated by the glomerular filtration rate.
In some examples, the level of the fat factor Ism1 is inversely related to glomerular filtration rate.
In some examples, the higher the level of the fat factor Ism1, the higher the staging of kidney function.
In some examples, the level of Ism1 in serum is greater than 1.259ng/mL and the glomerular filtration rate is less than 90mL/min/1.73m 2 And (5) correlation. Thus, when it is detected that the Ism1 level in serum is greater than 1.259ng/mL, it is possible to evaluate the glomerular filtration rate to be less than 90mL/min/1.73m 2 。
In some examples, the level of Ism1 in serum is greater than 1.297ng/mL and the glomerular filtration rate is less than 60mL/min/1.73m 2 And (5) correlation. Thus, when it is detected that the Ism1 level in serum is greater than 1.297ng/mL, it is possible to evaluate the glomerular filtration rate to be less than 60mL/min/1.73m 2 。
In some examples, the level of Ism1 in serum is greater than 1.419ng/mL and the glomerular filtration rate is less than 30mL/min/1.73m 2 And (5) correlation. Thus, when it is detected that the Ism1 level in serum is greater than 1.419ng/mL, it is possible to evaluate the glomerular filtration rate to be less than 30mL/min/1.73m 2 。
In some examples, glomerular filtration rate is less than 90mL/min/1.73m at Ism1 levels greater than 1.259ng/mL in serum 2 The sensitivity of (2) was 59.30% and the specificity was 84.55%. In some examples, glomerular filtration rate is less than 60mL/min/1.73m at Ism1 levels greater than 1.297ng/mL in serum 2 The sensitivity of (2) was 92.86% and the specificity was 83.83%. In some examples, glomerular filtration rate is less than 30mL/min/1.73m at Ism1 levels greater than 1.419ng/mL in serum 2 The sensitivity of (2) was 100% and the specificity was 83.42%.
In some examples, a level of Ism1 greater than 1.259ng/mL in the serum correlates with a renal function stage being in the second phase of renal function, the third phase of renal function, the fourth phase of renal function, or the fifth phase of renal function. Thus, when a serum Ism1 level greater than 1.259ng/mL is detected, it can be assessed that the renal function segment is in the second, third, fourth or fifth phase of renal function.
In some examples, a level of Ism1 in the serum of greater than 1.297ng/mL correlates with a renal function stage being in the third phase, the fourth phase, or the fifth phase of renal function. Thus, when an Ism1 level of greater than 1.297ng/mL in serum is detected, it can be assessed that the renal function segment is in the third, fourth, or fifth phase of renal function.
In some examples, a serum Ism1 level of greater than 1.419ng/mL correlates with a renal function stage being in the fourth phase of renal function or the fifth phase of renal function. Thus, when an Ism1 level of greater than 1.419ng/mL in serum is detected, it can be assessed that the renal function segment is in the fourth phase of renal function or the fifth phase of renal function.
In some examples, the sensitivity of the kidney function stage in the second, third, fourth, or fifth phase of kidney function is 59.30% and the specificity is 84.55% at an Ism1 level greater than 1.259ng/mL in serum. In some examples, the sensitivity of the renal function stage at the third, fourth, or fifth stage of renal function is 92.86% and the specificity is 83.83% at Ism1 levels greater than 1.297ng/mL in serum. In some examples, the sensitivity of the renal function stage at either the fourth phase or the fifth phase of renal function is 100% and the specificity is 83.42% at Ism1 levels greater than 1.419ng/mL in serum.
The disclosure also relates to the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing glomerular filtration rate. Thus, the glomerular filtration rate can be evaluated by detecting the level of the fat factor Ism1, thereby facilitating the subsequent use of the glomerular filtration rate to evaluate renal function in diabetics.
The disclosure also relates to the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent that predicts the risk of progression of renal function. Thus, the risk of progression of renal function can be predicted by detecting the level of the fat factor Ism1, and thus, the therapeutic strategy can be adjusted with ease and the management of the disease can be facilitated.
In some examples, it may refer to the use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent that predicts the risk of progression of renal function in a diabetic patient. Thus, the risk of renal function progression in a diabetic patient can be predicted by detecting the level of the fat factor Ism 1.
In some examples, the risk of renal function progression may refer to a risk of a staged increase in renal function. In some examples, the risk of renal function progression may refer to the risk of a renal function progression endpoint event, i.e., may refer to the risk of renal function progression to stage five.
In some examples, kidney function progression is at high risk when Ism1 levels in serum are greater than 1.249 ng/mL.
In some examples, when the Ism1 level in the serum is greater than 1.249ng/mL, the risk of progression to the fifth phase of renal function is high.
In some examples, when the Ism1 level in serum is greater than 1.249ng/mL, renal function is able to progress to a sensitivity of 87.5% at stage v, with a specificity of 69.44%. Thus, the risk of progression of renal function can be predicted by detecting the level of Ism1 in serum.
The above applications to which the present disclosure relates are further explained in detail below in connection with examples, but they should not be construed as limiting the scope of the present disclosure.
Examples (example)
In this example, unless otherwise indicated, materials, reagents, instruments and software used were all those commercially available and the procedure was carried out according to the instructions for the reagents, instruments or software.
Example 1
(1) The subject:
clinical data were collected for a total of 888 type 2 diabetics, excluding non-standard patients, and a total of 209 type 2 diabetics were ultimately included as subjects in this example. Wherein, the exclusion criteria were: 1. liver function insufficiency. 2. Severe infection or malignancy. 3. Other types of diabetes. 4. Ketoacidosis or non-ketosis hypertonic syndrome. 5. The age is less than 40 years old or the course of the disease is less than 1 month. 6. Fasting C peptide was less than 0.3ng/mL.7. Fasting blood glucose is greater than 8.0mmol/L.
(2) And (3) detection:
the level of the fat factor Ism1 in the subject was measured and the glomerular filtration rate was estimated.
Wherein the step of detecting the level of the fat factor Ism1 in the subject comprises:
a) Venous blood collection: the blood collection is preferably carried out for at least 8 hours, preferably 12 to 14 hours, but not more than 16 hours; taking the elbow vein as a blood sampling part, and optionally selecting a naked vein in a back vein, and sterilizing the blood sampling part, including surrounding skin, by using povidone iodine; after drying, puncturing and collecting blood; after the collection is finished, the collected part is stopped by using a sterile cotton ball, and then the collected sample is put into a separation coagulation accelerating tube with a label, and the machine feeding and the centrifugation are carried out within 2 hours;
b) And (3) centrifuging: after the blood sample was coagulated, centrifugation was performed at 3500 rpm for 10 minutes;
c) Serum separation: opening a blood collection tube in a biosafety cabinet, carefully transferring serum into a clean and dry sterile EP centrifuge tube with the concentration of 1.5 ml to 2 ml by using a pipettor, taking care not to pour (or transfer) a blood coagulation block, marking patient information on the EP centrifuge tube by using an oily marker pen, and placing numbered serum into a refrigerated cabinet with the temperature of 2 ℃ to 8 ℃ for detection;
4. detecting the concentration of the fat factor Ism1 in the serum of the subject: the concentration of the adipokine Ism1 in serum was measured according to the product instructions using an ELISA kit (Mybiosource, usa).
Wherein the glomerular filtration rate (GFR or eGFR) of the subject is calculated by CKD-EPI formula, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula is a formula for estimating glomerular filtration rate in mL/min/1.73m 2 This formula takes into account factors such as plasma creatinine concentration, age, race and gender to provide a more accurate GFR estimate. The CKD-EPI formula is specifically as follows:
GFR＝α×(Scr/b) c ×0.993 Age 。
in the formula, scr (Serum creatinine) represents serum creatinine concentration (in mg/dL, i.e., milligrams per deciliter) obtained by detecting the level of creatinine in the serum of a subject, in this example by detecting the serum of a subject using a creatinine assay kit. In the formula, the variable α depends on race and gender, α=166 in case of african females in the united states; in case of african men in the united states, α=163; in the case of white or other ethnic females, α=144; in the case of white or other ethnic men, α=141. Variable b depends on sex, b=0.7 in the case of females; in the case of male, b=0.9. The variable c depends on sex and serum creatinine concentration, if female and serum creatinine concentration is less than or equal to 0.7mg/dL, c= -0.329; if female and serum creatinine concentration > 0.7mg/dL, c= -1.209; if the male animal is male and the serum creatinine concentration is less than or equal to 0.9mg/dL, c= -0.411; if male and serum creatinine concentration > 0.9mg/dL, c= -1.209. In the formula, age represents Age (in years).
(3) Analysis of results:
the kidney function is generally divided into 5 periods, the first period of the kidney function, and the glomerular filtration rate is more than or equal to 90mL/min/1.73m 2 Kidney function is normal, and only trace amounts of proteinuria can be detected; renal function second phase, 60mL/min/1.73m 2 Glomerular filtration rate less than or equal to 90mL/min/1.73m 2 Belongs to mild renal failure; kidney function stage III, 30mL/min/1.73m 2 Glomerular filtration rate less than or equal to 60mL/min/1.73m 2 Belongs to moderate renal failure; kidney function stage IV, 15mL/min/1.73m 2 Glomerular filtration rate less than or equal to 30mL/min/1.73m 2 Belongs to severe renal failure; the fifth stage of renal function, the glomerular filtration rate is less than 15mL/min, belongs to the final stage of renal failure, namely uremia stage.
In view of this, the subjects of the examples were classified into the following five groups according to the glomerular filtration rate estimation results: group G1 (glomerular filtration rate is not less than 90mL/min/1.73 m) 2 ) Group G2 (60 mL/min/1.73 m) 2 Glomerular filtration rate less than or equal to 90mL/min/1.73m 2 ) G3 group (glomerular filtration rate is less than or equal to 30 and less than 60mL/min/1.73 m) 2 ) G4 group (glomerular filtration rate is 15-30 mL/min/1.73 m) 2 ) Group G5 (glomerular filtration rate)<15mL/min/1.73m 2 ) Statistical analysis was performed using analysis software SPSS 25.0.
Fig. 1 is a schematic diagram showing serum Ism1 level results of G1-2 groups (referred to as G1 to G2 groups, i.e., G1 group and G2 group) and G3-5 groups (referred to as G3 to G5 group, i.e., G3 group, G4 group and G5 group) according to the embodiments of the present disclosure, fig. 2 is a schematic diagram showing serum Ism1 level results of G1 group, G2 group, G3 group and G4-5 group (referred to as G4 to G5 group, i.e., G4 group and G5 group) according to the embodiments of the present disclosure, fig. 3 is a schematic diagram showing linear fitting results of serum Ism1 levels and glomerular filtration rate according to the embodiments of the present disclosure, and fig. 4 is a ROC graph showing evaluation of glomerular filtration rate by Ism1 according to the embodiments of the present disclosure. As shown in fig. 1, 2, 3 and 4:
serum Ism1 levels were significantly higher in groups G3 to G5 than in groups G1 to G2, p <0.001. Serum Ism1 levels of group G3 are higher than that of group G1 or group G2, serum Ism1 levels of groups G4 to G5 are higher than that of group G1 or group G2, and P <0.001. From this, it was found that serum Ism1 levels were significantly correlated with glomerular filtration rate; serum Ism1 levels are associated with renal function staging in diabetics; the higher the serum Ism1 level, the higher the renal function stage in diabetics.
Analysis of a binary logics regression model shows that after the age, sex, body mass index, fasting C peptide, systolic pressure and other influencing factors are corrected, the serum Ism1 level is increased and GFR is improved<60mL/min/1.73m 2 The occurrence of events is correlated (or=1.546; p<0.001 For each 1ng/mL increase in serum Ism1 levels, GFR)<60mL/min/1.73m 2 The occurrence probability of the event is increased by 54.6%.
Linear regression analysis showed that serum Ism1 levels correlated negatively with GFR (regression coefficients β= -19.289, p < 0.01) after correction of age, sex, body mass index, fasting C-peptide, systolic blood pressure, etc. Thus, glomerular filtration rate can be assessed by serum Ism1 levels.
ROC curve (receiver operating characteristic curve, subject working characteristics) shows: evaluation of eGFR with Ism1<90mL/min/1.73m 2 The optimal critical point is: 1.259ng/mL, AUC (Area Under Curve) of 0.761, optimum sensitivity of 59.30%, specificity of 84.55%; evaluation of eGFR with Ism1<60mL/min/1.73m 2 AUC at 0.908, optimal critical point (Optimal Operating Point, also called optimal working point) of 1.297ng/mL, mostThe optimal sensitivity is 92.86 percent, and the specificity is 83.83 percent; evaluation of eGFR with Ism1<30mL/min/1.73m 2 When the optimal critical point is 1.419ng/mL, the AUC is 0.915, the optimal sensitivity is 100%, and the specificity is 83.42%; the p values are all less than 0.001. Therefore, the glomerular filtration rate is evaluated by the serum Ism1 level, and the kit has better sensitivity and specificity.
Example 2:
the 209 type 2 diabetics enrolled in example 1 were followed up, 121 out of the non-enrolled patients, 88 patients were enrolled together, the median follow-up time was 20.00 weeks, and the end-stage (i.e. G5 phase) of the increase in serum creatinine concentration by 30% or diabetic nephropathy was defined as an endpoint event, for 16 patients.
Fig. 5 is a ROC graph showing an Ism1 prediction of end-point events related to renal function progression according to embodiments of the present disclosure, and fig. 6 is a schematic diagram showing the results of Kaplan-Meier analysis of an Ism1<1.249ng/mL group and an Ism1 ≡1.249ng/mL group according to embodiments of the present disclosure, where the Kaplan-Meier analysis is a statistical method for estimating survival analysis and survival probability, and is suitable for studying time of occurrence of an event (such as death of a patient, recurrence of disease, etc.) and observation time period before occurrence of the event.
As shown in fig. 5, the ROC curve shows: when the serum Ism1 level is used for predicting the end-point event related to the renal function progression, p is less than 0.001, AUC is 0.799, the optimal critical point is 1.249ng/mL, the optimal sensitivity is 87.50%, and the specificity is 69.44%. Therefore, the end-point event related to the renal function progression can be predicted by the serum Ism1 level, and the end-point event related to the renal function progression can be predicted by the serum Ism1 level, so that the sensitivity and the specificity are better.
As shown in FIG. 6, kaplan-Meier analysis showed that: serum Ism1 levels exceeding 1.249ng/mL are to some extent predictive of the occurrence of the above-described endpoint events associated with renal function progression, p <0.001. From this, it was found that the serum Ism1 level was correlated with an endpoint event related to the progression of renal function, and that the risk of progression of renal function could be predicted from the serum Ism1 level.
In summary, in the present disclosure, the relationship between the level of the fat factor Ism1 and glomerular filtration rate and renal function was studied, and the renal function of a diabetic patient can be evaluated by detecting the level of the fat factor Ism 1; glomerular filtration rate can be assessed by detecting the level of the fat factor Ism 1; the risk of progression of renal function can be predicted by detecting the level of the fat factor Ism 1. Thus, it is possible to provide an application of a substance detecting the level of fat factor Ism1 in the preparation of a reagent for evaluating renal function, an application of a substance detecting the level of fat factor Ism1 in the preparation of a reagent for evaluating glomerular filtration rate, and an application of a substance detecting the level of fat factor Ism1 in the preparation of a reagent for predicting risk of progression of renal function.
While the disclosure has been described in detail in connection with the drawings and embodiments, it should be understood that the foregoing description is not intended to limit the disclosure in any way. Modifications and variations of the present disclosure may be made as desired by those skilled in the art without departing from the true spirit and scope of the disclosure, and such modifications and variations fall within the scope of the disclosure.

Claims (10)

1. Use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent for assessing renal function in a subject.
2. The use according to claim 1, wherein the glomerular filtration rate is assessed by detecting the level of the fat factor Ism1, thereby assessing renal function in the subject.
3. The use according to claim 1 or 2, wherein the subject is a kidney disease patient.
4. The use according to claim 3, wherein the subject is a diabetic nephropathy patient.
5. The use according to claim 2, wherein the level of the fat factor Ism1 is inversely related to glomerular filtration rate.
6. The use according to claim 1 or 2, wherein the substance is used for detecting the level of the adipokine Ism1 in the serum of the subject.
7. The use according to claim 6, wherein the level of the fat factor Ism1 is detected by enzyme-linked immunosorbent assay.
8. Use of a substance that detects the level of the fat factor Ism1 for the preparation of a reagent for assessing glomerular filtration rate.
9. Use of a substance that detects the level of the fat factor Ism1 in the preparation of a reagent that predicts the risk of progression of renal function.
10. The use according to claim 9, wherein the level of the fat factor Ism1 is greater than 1.249ng/mL, the risk of renal function progression is high.
CN202311202087.6A 2023-08-22 2023-09-18 Application of substance for detecting fat factor Ism1 level in preparation of reagent for evaluating renal function of subject Pending CN117310179A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190242908A1 (en) * 2016-09-08 2019-08-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosing and treating nephrotic syndrome
CN113584175A (en) * 2021-08-30 2021-11-02 南京大学 Group of molecular markers for evaluating renal papillary cell carcinoma progression risk and screening method and application thereof

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Publication number Priority date Publication date Assignee Title
US20190242908A1 (en) * 2016-09-08 2019-08-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosing and treating nephrotic syndrome
CN113584175A (en) * 2021-08-30 2021-11-02 南京大学 Group of molecular markers for evaluating renal papillary cell carcinoma progression risk and screening method and application thereof

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