Peritoneal function evaluation marker, peritoneal function evaluation kit, and peritoneal dialysis drainage measurement method

Abstract

To provide a peritoneal function evaluation marker, peritoneal function evaluation kit, and peritoneal dialysis drainage measurement method that can measure D / P Cr or D / D0 Glu by a PET or an amount of drainage by a peritoneal dialysis upon implementing an ordinary peritoneal dialysis, by a simple method, and by a simple index, or can evaluate a peritoneal function equaling to a measurement of dip Na, and what is more, can take an appropriate action to prolong a peritoneal dialysis period as long as possible, and can contribute to improvement in quality of life of a patient, and an extention of the peritoneal dialysis period and life expectancy period, and improvement in medical economy.SOLUTION: A peritoneal function evaluation marker is composed of autotaxin. A peritoneal function evaluation kit includes a reagent that detects the peritoneal function evaluation marker composed of the autotaxin. A peritoneal dialysis drainage measurement method is configured to detect the peritoneal function evaluation marker composed of the autotaxin in peritoneal dialysis drainage.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention is used in an accurate and simple method for assessing the peritoneal function of a peritoneal dialysis patient, and relates to a peritoneal function evaluation marker, a peritoneal function evaluation kit for measuring the marker, and a method for measuring peritoneal dialysis effluent. [Background technology]

[0002] The kidneys are responsible for excreting waste products (such as blood waste products such as creatinine) and excess water intake as urine, and maintaining a constant level of bodily fluids. When the kidneys are damaged and their function gradually declines due to factors such as diabetes or nephrosclerosis, the patient develops end-stage renal failure and develops symptoms such as uremia.

[0003] Patients with chronic renal failure whose renal function has fallen below approximately 10% undergo artificial dialysis, such as peritoneal dialysis and hemodialysis, to supplement the reduced renal function and remove waste products and fluids.

[0004] Peritoneal dialysis is a therapy that is started while kidney function is still relatively intact. Dialysis fluid is temporarily introduced into the abdominal cavity, which is surrounded by the peritoneum that covers the surfaces of internal organs such as the liver, stomach, and intestines and the inner surface of the abdominal wall, through a dialysis catheter for a certain period of time. Waste products and excess water in the blood are transferred from the intraperitoneal capillaries in the abdominal cavity through the peritoneum to the intraperitoneal dialysis fluid. Once the waste products and water have been sufficiently transferred to the dialysis fluid, the intraperitoneal dialysis fluid is removed from the body through the dialysis catheter and drained, thereby purifying the blood.

[0005] On the other hand, hemodialysis is also a therapy performed on patients with chronic renal failure whose kidney function has fallen below approximately 10%. In this therapy, blood is circulated through the inside of hollow fibers made of semipermeable membranes in a dialysis machine called a dialyzer, and waste products and excess water in the blood are transferred by diffusion, ultrafiltration, and osmotic pressure to the dialysis fluid flowing on the outside of the hollow fibers, thereby purifying the blood.

[0006] It is said that there are about 350,000 dialysis patients, and the number is increasing by about 10,000 each year. Of these dialysis patients, about 9,000 are peritoneal dialysis patients. Peritoneal dialysis is a treatment that contributes to improving life prognosis by preserving residual renal function and reducing the burden on the cardiovascular system more than hemodialysis, and it is also desirable to increase the number of peritoneal dialysis patients from a medical economic perspective. In addition, peritoneal dialysis is a dialysis therapy that can be performed at home, and is excellent as medical care during disasters and in an aging society. However, the increase in new peritoneal dialysis patients has plateaued at about 2,000 each year, and the majority of the remaining dialysis patients, including new hemodialysis patients, are hemodialysis patients.

[0007] The advantages of peritoneal dialysis are that it can relatively maintain residual renal function, puts less strain on the cardiovascular system, and therefore contributes to improving life prognosis, as well as fewer unbalanced symptoms, short time constraints, and is favorable for returning to society, with little impact on quality of life and high patient satisfaction. On the other hand, the disadvantage of peritoneal dialysis is that it is difficult to continue for the long term due to a decline in peritoneal function, and patients must switch to hemodialysis after 4 to 10 years. This disadvantage is thought to be one of the reasons why peritoneal dialysis is not chosen, and the evaluation and prediction of decline in peritoneal function is an important issue.

[0008] Waste solutes in the blood in the capillary cavity, such as creatinine (Cr), which can no longer be excreted due to decreased renal function, diffuse through the semipermeable peritoneal membrane into the peritoneal dialysis fluid, where they become the same concentration and are removed. As a result, the waste solutes in the blood decrease and the blood becomes cleaner. On the other hand, excess water that has accumulated in the body and is no longer excreted due to decreased renal function is removed by the water moving from the blood in the capillary cavity to the intraperitoneal dialysate so that the osmotic pressures are equal, since blood contains glucose (Glu) and has an osmotic pressure of 280 mOsm, while the intraperitoneal dialysate also contains excess glucose and has an osmotic pressure of 340 to 480 mOsm.

[0009] In routine clinical practice, peritoneal function is evaluated by the peritoneal equilibration test (PET), specifically, the creatinine removal rate: D / P Cr = (creatinine concentration in the peritoneal dialysate 4 hours after the start of the test: D Cr) ÷ (creatinine concentration in the blood: P Cr) and the glucose absorption rate: D / D0Glu = (glucose concentration in the peritoneal dialysate 4 hours after the start of the test: D Glu) ÷ (glucose concentration in the dialysate at the beginning of the test: D0Glu).

[0010] D / P Cr is used to observe whether creatinine has moved from blood (especially plasma) to the dialysis fluid, so the higher the ratio, the higher the peritoneal permeability (high) and the lower the ratio, the lower the peritoneal permeability (low). On the other hand, D / D0Glu is used to observe the movement of glucose from the dialysis fluid to the blood, so the lower the ratio, the higher the peritoneal permeability (high) and the higher the ratio, the lower the peritoneal permeability (low). The higher the peritoneal permeability, the greater the movement of glucose from the dialysis fluid to the blood, which reduces the osmotic pressure difference and reduces the water removal ability, and the lower the peritoneal permeability, the easier it is for glucose to be retained in the dialysis fluid and the osmotic pressure difference is maintained, resulting in a higher water removal ability.

[0011] Peritoneal dysfunction is characterized by insufficient water removal and excessive solute transport, and is the main cause of weaning from peritoneal dialysis. Therefore, increased peritoneal permeability is associated with peritoneal dysfunction (see Non-Patent Documents 1 and 2). Peritoneal function shows increased permeability over time. In other words, peritoneal function declines over time. Patients must switch to hemodialysis due to peritoneal dysfunction, and measures must be taken to maintain peritoneal function during this time, so an index for correctly evaluating peritoneal function is required.

[0012] Such D / P Cr and D / D0Glu by PET are widely used as indicators to accurately evaluate peritoneal function, but it is a complicated procedure in which after injecting 1500 mL of 2.5% glucose-containing peritoneal dialysis fluid, the amount of drained fluid is recorded at time 0 (immediately after the start of the test), the creatinine and glucose concentrations in the collected blood and the drained dialysate are measured 1 and 2 hours later, and the creatinine and glucose concentrations in the drained dialysate and the amount of drained fluid are measured 4 hours later.

[0013] In recent years, it has been reported that a decrease in the Na concentration in the effluent dialysate (dip Na) in a one-hour PET test (Mini-PET) can be a predictor of fluid removal failure (see Non-Patent Documents 2 and 3). Although the time is shorter than that of regular PET, the need for one-hour retention imposes time constraints and requires complicated procedures, which are problematic.

[0014] The present inventors have reported that autotaxin (ATX) is extravasated due to increased vascular permeability during the progression of renal fibrosis caused by unilateral renal ligation (see Non-Patent Document 4). In peritoneal dialysis, increased vascular permeability of the peritoneum is said to contribute to decreased peritoneal function due to peritoneal fibrosis, but the relationship between peritoneal function and autotaxin is completely unknown. [Prior art documents] [Non-patent literature]

[0015] [Non-Patent Document 1] Brown EA, et al. J Am Soc Nephrol; 14: 2948-2957, 2003 [Non-Patent Document 2] La Milla, et al. Kidney Int; 69: 927-933, 2006 [Non-Patent Document 3] La Milla, et al. Kidney Int; 68: 840-846, 2005 [Non-Patent Document 4] Sakai N, et al. Sci Rep; 9: 7414, 2019 Summary of the Invention [Problem to be solved by the invention]

[0016] There was a need for a simple indicator that could evaluate peritoneal function equivalent to PET measurements of D / P Cr, D / D0Glu, and drainage volume, or dip Na, without relying on these.

[0017] The present invention has been made to solve the above problems. That is, a simple sample collection method using only the dialysis fluid drainage during normal peritoneal dialysis can be used to measure the autotaxin concentration in the dialysis effluent, and the peritoneal function can be evaluated equivalent to the measurement of D / P Cr, D / D0Glu, and effluent volume by PET, or the measurement of dip Na, and by simply and appropriately evaluating the peritoneal function, it is possible to appropriately take measures to extend the peritoneal dialysis period as much as possible, thereby improving the quality of life of patients, extending the peritoneal dialysis period and life expectancy, and improving medical economy. The purpose of the present invention is to provide a peritoneal function evaluation marker, a peritoneal function evaluation kit, and a method for measuring peritoneal dialysis effluent. [Means for solving the problem]

[0018] In order to achieve the above-mentioned object, a peritoneal function evaluation marker consisting of autotaxin has been developed.

[0019] This peritoneal function evaluation marker is, for example, one in which the autotaxin is present in peritoneal dialysis effluent.

[0020] It is preferable that this peritoneal function evaluation marker is one for evaluating at least one indicator selected from the possibility of continuing peritoneal dialysis and the predictability of transition to hemodialysis.

[0021] The peritoneal function evaluation marker preferably has a threshold value of more than 1.5 ng / ml, which can be used as a marker that peritoneal function is insufficient for peritoneal dialysis.

[0022] The peritoneal function evaluation kit devised to achieve the above-mentioned object contains a reagent for detecting a peritoneal function evaluation marker consisting of autotaxin.

[0023] In this peritoneal function evaluation kit, the reagent contains an anti-autotaxin monoclonal antibody and an enzyme-labeled reagent of the anti-autotaxin monoclonal antibody.

[0024] The method for measuring peritoneal dialysis effluent devised to achieve the above-mentioned object involves detecting a peritoneal function evaluation marker consisting of autotaxin in the peritoneal dialysis effluent.

[0025] In this method for measuring peritoneal dialysis effluent, the peritoneal function evaluation marker is preferably at least one indicator selected from the group consisting of the possibility of continuing peritoneal dialysis and the predictability of transition to hemodialysis.

[0026] In this method for measuring peritoneal dialysis effluent, for example, the peritoneal function evaluation marker is measured using an anti-autotaxin monoclonal antibody and an enzyme-labeled reagent of the anti-autotaxin monoclonal antibody. Effect of the Invention

[0027] The peritoneal function evaluation marker of the present invention is a simple method that uses the effluent dialysate from normal peritoneal dialysis and is already covered by insurance as a liver fibrosis marker in blood, and uses a simple indicator called autotaxin to evaluate peritoneal function equivalent to or better than the measurement of D / P Cr, D / D0Glu, and effluent volume by PET, or dip Na, which are conventionally performed during hospitalization for examination, without the need for troublesome procedures such as hospitalization for examination.

[0028] Furthermore, since the measurement of peritoneal function evaluation markers measures the concentration in the peritoneal dialysis fluid during normal peritoneal dialysis, it is non-invasive, does not impose an excessive burden on the patient, and does not require troublesome procedures such as hospitalization just for the test.

[0029] Furthermore, by measuring this peritoneal function evaluation marker, it is possible to take appropriate measures to extend the peritoneal dialysis period as long as possible by appropriately selecting a dialysis fluid with a low glucose concentration that is gentle on the patient's body, thereby improving dialysis efficiency, while delaying the use of dialysis fluid with a high glucose concentration, thereby reducing the burden on the peritoneum, thereby improving the patient's quality of life and extending the duration of peritoneal dialysis and life expectancy.

[0030] Furthermore, the timing of transition to hemodialysis can be delayed, and peritoneal function can be easily examined with a simple test, so even if insurance is applied and the number of tests ordered increases, it will be inexpensive and will contribute to improving medical economics.

[0031] Measuring this peritoneal function evaluation marker will enable simple evaluation of peritoneal function, which is expected to expand the peritoneal dialysis market and extend life expectancy through peritoneal dialysis and subsequent transition to hemodialysis.

[0032] Furthermore, according to the peritoneal function evaluation kit and the method for measuring peritoneal dialysis effluent of the present invention, autotaxin, which is a peritoneal function evaluation marker, can be measured simply and simply, reliably and accurately in a short period of time, thereby enabling correct evaluation of peritoneal function. [Brief description of the drawings]

[0033] [Figure 1] 1 is a schematic diagram showing an outline of the elapsed time and operations of a peritoneal dialysis test for measuring autotaxin, which is a peritoneal function evaluation marker in an embodiment to which the present invention is applied, and dip Na in a control example to which the present invention is not applied. [Diagram 2] 1 is a schematic diagram outlining the time course and procedures of a control peritoneal dialysis study for a PET method not in accordance with the present invention. [Diagram 3] 1 is a graph showing the correlation between autotaxin, which is a marker for evaluating peritoneal function in an example in which the present invention is applied, and D / P Cr and D / D0 Glu in a PET method to which the present invention is not applied. [Figure 4]1 is a graph showing the correlation between autotaxin, which is a peritoneal function evaluation marker in an example in which the present invention is applied, and dip Na in an example in which the present invention is not applied. [Diagram 5] 1 is a graph showing the correlation between autotaxin, which is a marker for evaluating peritoneal function, and Net UF in an example in which the present invention is applied. [Figure 6] 1 is a graph showing the correlation between autotaxin, which is a marker for evaluating peritoneal function, and the change in Net UF in an example in which the present invention is applied. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] Hereinafter, the embodiments for carrying out the present invention will be described in detail, however, the scope of the present invention is not limited to these examples.

[0035] The peritoneal function evaluation marker of the present invention is composed of autotaxin. Autotaxin is a synthetic enzyme (a type of lysophospholipase D) of lysophosphatidic acid, which is one of lipid mediators. Autotaxin is extravasated due to increased vascular permeability during the progression of renal fibrosis due to unilateral kidney ligation. Therefore, autotaxin is leaked into the dialysis fluid due to increased vascular permeability of the peritoneum, and the hypothesis was established that the concentration in the dialysis effluent correlates with peritoneal function. As a result, the correlation was confirmed, and it was found to be useful as a peritoneal function evaluation marker. This led to the completion of the present invention.

[0036] Autotaxin is thought to be expressed at sites of increased vascular permeability because it leaks out of the blood vessels due to increased vascular permeability during the progression of renal fibrosis caused by unilateral renal ligation. Although the mechanism of the relationship between increased peritoneal permeability in the peritoneum and autotaxin concentration in peritoneal dialysis effluent is not entirely clear, it is speculated that autotaxin leaked out of the blood vessels due to increased peritoneal vascular permeability migrates into the peritoneal dialysis fluid, causing an increase in the autotaxin concentration in the peritoneal dialysis effluent.

[0037] Autotaxin, a marker for evaluating peritoneal function, can be measured by fluorescent enzyme immunoassay using the sandwich method, chemiluminescent enzyme immunoassay, or enzyme method, and can be used as a marker for evaluating peritoneal function when measured in the effluent dialysate from peritoneal dialysis.

[0038] Autotaxin can be measured using an anti-autotaxin monoclonal antibody and an enzyme-labeled reagent of the anti-autotaxin monoclonal antibody.

[0039] Autotaxin is a marker for evaluating peritoneal function, which is measured by pre-accumulating it in peritoneal dialysis fluid 8 to 12 hours before the test, then draining it on the day of the test. In this way, it can be measured quickly and easily in a short time, and since it is a shorter test than the conventional PET method or Mini-PET method, there is no need for hospitalization for the test, and it can be measured during normal peritoneal dialysis. In addition, there is no invasive burden on dialysis patients, and the test time can be shortened.

[0040] The autotaxin concentration was found to correlate significantly with the results of peritoneal permeability enhancement in D / P Cr and D / D0Glu measured from the drainage 4 hours after pre-storage with peritoneal dialysis fluid 8-12 hours before the examination using PET after admission to the hospital as in the past, and then drained and immediately injected with peritoneal dialysis fluid on the day of the examination.In addition, a significant correlation was found with the results of peritoneal function enhancement in Dip Na measured from the drainage 1 hour after pre-storage with peritoneal dialysis fluid 8-12 hours before the examination using Mini-PET, and then drained and immediately injected with peritoneal dialysis fluid on the day of the examination.

[0041] Autotaxin concentration can be measured frequently from the effluent, allowing for a simple evaluation of peritoneal function. A simple evaluation of peritoneal function allows for the appropriate selection of a dialysis fluid with a low glucose concentration that is gentle on the patient's body, and the timing of using a dialysis fluid with a high glucose concentration can be delayed, reducing the burden on the peritoneum and extending the duration of peritoneal dialysis. Furthermore, the longer the duration of peritoneal dialysis, the more likely it is that the patient's quality of life will be improved by delaying the transition to long-term hemodialysis, which requires time constraints of 3 to 4 hours per session and is performed three times a week.

[0042] Furthermore, if autotaxin is measured as a marker for evaluating peritoneal function, even in cases where patients previously chose hemodialysis even though they could have started with either peritoneal dialysis or hemodialysis, resulting in early loss of residual renal function, they will now be able to safely choose peritoneal dialysis first and continue peritoneal dialysis for the long term while preserving as much residual renal function as possible.

[0043] Furthermore, if the measurement of autotaxin as a marker for evaluating peritoneal function becomes established, it can be used as a correct evaluation of peritoneal function, expanding the peritoneal dialysis market; peritoneal dialysis will be performed initially, and when peritoneal dialysis function declines, patients will be switched to hemodialysis, thereby extending the life expectancy of dialysis patients, which was previously said to be about half of the average life expectancy.

[0044] Furthermore, the evaluation kit for peritoneal dialysis function for measuring this autotaxin as a peritoneal function evaluation marker is specifically an ELISA method using a sandwich method for measuring by fluorescent enzyme immunoassay or chemiluminescent enzyme immunoassay, which uses an anti-autotaxin monoclonal antibody and an enzyme-labeled reagent of the anti-autotaxin monoclonal antibody, and causes an antigen-antibody reaction between the autotaxin in the effluent dialysis fluid and the anti-autotaxin monoclonal antibody, and if necessary, collects the complex with a magnetic force and washes to remove unreacted substances, and then reacts with an enzyme-labeled antibody, which is an enzyme-labeled reagent, and if necessary, washes in the same manner to remove unreacted substances, and then adds a chemiluminescent substrate to measure the amount of luminescence produced by hydrolysis with the enzyme in the complex, or instead uses a labeled antibody of a chemiluminescent compound. More specifically, examples of the kit include the Autotaxin Activity Assay, Autotaxin Sandwich ELISA Kit, and Autotaxin Inhibitor Screening Kit manufactured by Echelon Biosciences Inc., the ENPP-2 DuoSet Kit manufactured by R&D Systems, Inc., and the AIA-Pack CL manufactured by Tosoh Corporation. One such product is called Autotaxin.

[0045] In addition, the concentration of the peritoneal function evaluation marker, autotaxin, in the effluent dialysis is considered to be the threshold value of at least one of the indicators selected from the possibility of continuing peritoneal dialysis and the predictability of transition to hemodialysis when it exceeds 1.5 ng / ml. Referring to the regression line in Figure 3, when autotaxin exceeds 1.5 ng / mL, it is close to the value at which D / P Cr and D / D0 Glu are high. From this, when it exceeds 1.5 ng / ml, the function of the peritoneum may be deteriorated and it may become difficult to continue peritoneal dialysis because it is no longer suitable for peritoneal dialysis, and it becomes necessary to transition from peritoneal dialysis to hemodialysis. EXAMPLES

[0046] Tests were carried out as follows for examples to which the present invention is applied and comparative examples to which the present invention is not applied. The results are shown below.

[0047] Example 1 ·subject The study participants were patients undergoing peritoneal dialysis who visited Kanazawa University Hospital and affiliated hospitals between May 2016 and March 2021. Written informed consent was obtained from all patients. ·Exclusion criteria In addition, the following patients were excluded: 1) patients with malignant tumors, 2) patients scheduled for kidney transplantation, 3) pregnant and lactating women, and 4) patients who did not give consent. Study Design This was a prospective cohort study. ·Patient background The number of cases was 45, the mean age was 69 years, 33 (73%) were male, and the mean duration of peritoneal dialysis was 32 months. The main underlying diseases of renal failure were diabetic nephropathy (15, 33%), benign nephrosclerosis (9, 20%), and IgA nephropathy (6, 13%). Testing Method The test method was based on the Mini-PET method and was shown in Figure 1. First, at 9 p.m. on the day before the measurement, 1,500 mL of peritoneal dialysis fluid containing 1.5% or 2.5% glucose (manufactured by Baxter, product name Regunyl, or manufactured by Terumo, product name MidPeric) was injected into the abdominal cavity of each patient. At 8 a.m. on the day of the measurement, the entire amount was drained and effluent sample 0 was collected while recording the amount of drainage. 1,500 mL of peritoneal dialysis fluid containing 2.5% glucose (manufactured by Baxter, product name Regunyl, or manufactured by Terumo, product name MidPeric) was injected and effluent sample 1 was collected as the initial value. At 9 a.m., the entire amount was drained and the amount of drainage was recorded, and effluent sample 2 was collected one hour later. For effluent sample 0, R&D Systems, Inc. Company-made Autotaxin concentrations were measured by ELISA using the Quantikine ELISA and Human ENPP-2 / Autotaxin Immunoassay kits.

[0048] (Control Example 1) According to Figure 1, instead of measuring the autotaxin concentration in the effluent dialysis fluid, the Na concentration was measured according to the standard method. DipNa = (Na concentration in drain 1) - (Na concentration in drain 2) was calculated.

[0049] (Control Example 2) The conventional PET method was performed according to the method shown in FIG. First, at 21:00 on the day before the measurement, 1.5% or 2.5% glucose-containing peritoneal dialysis solution (manufactured by Baxter; product name Regunyl, or manufactured by Terumo; product name MidPeric) 1500mL was injected into the abdominal cavity of each patient, and at 9:00 on the day of the measurement, the entire amount was drained and effluent sample 0 was collected while recording the amount of drainage. 2.5% glucose-containing peritoneal dialysis solution (manufactured by Baxter; product name Regunyl, or manufactured by Terumo; product name MidPeric) 1500mL was injected, effluent sample 1 was collected as the initial value and blood sampling 1 was also performed, effluent sample 2 was collected at 11:00 and blood sampling 2 was also performed, the entire amount was drained at 13:00, the amount of drainage was recorded, and effluent sample 3 was collected 4 hours later. The blood creatinine concentration was measured according to the usual method, and D / P Cr=(4hr D Cr)÷(P The glucose concentration in the dialysis fluid was measured by the usual method, and D / D0Glu = (4hr DGlu) ÷ (0hr D0Glu) was calculated. Furthermore, Net UF = (amount of drainage at 4 hours) - (amount of initial infusion) was calculated from the amount of drainage.

[0050] (Analysis 1: Cross-sectional analysis of autotaxin and PET markers) Since it was thought that there would be little change over a short period of time, a cross-sectional analysis was performed on the correlation between PET markers and autotaxin concentrations during the first PET and mini-PET performed after the start of observation on separate days. As shown in Figure 3, autotaxin concentrations showed a positive correlation with D / P Cr and D / D0Glu, with a correlation coefficient of r = 0.496 and a significant difference of p < 0.001, respectively, and a negative correlation with a correlation coefficient of r = -0.514 and a significant difference of p < 0.001, respectively.

[0051] (Analysis 2: Cross-sectional analysis of autotaxin and dip Na) A cross-sectional analysis was performed on the relationship between dip Na and autotaxin concentrations during the first mini-PET performed after the start of observation. As shown in Figure 4, autotaxin concentrations and dip Na showed a negative correlation with a correlation coefficient of r = -0.366 and a significant difference of p = 0.013.

[0052] (Analysis 3: Multivariate linear regression analysis of autotaxin and PET markers) Multivariate linear regression analysis was performed to examine the association between PET markers and autotaxin concentrations during the first PET and mini-PET scans from the start of observation. ATX was significantly correlated with D / P Cr, D / D0Glu, and dip Na, even after adjusting for many clinical factors.

[0053] (Analysis 4: Cross-sectional analysis of autotaxin and Net UF) A cross-sectional analysis was performed to examine the association between PET markers and autotaxin concentrations during the first PET and mini-PET performed after the start of observation. As shown in Figure 5, no correlation was found between autotaxin concentrations and the amount of Net UF.

[0054] (Analysis 5: Longitudinal analysis of autotaxin and Net UF) However, in 19 cases in which data was obtained over a one-year period, a longitudinal analysis was performed on the autotaxin concentration at the start of observation and the change in Net UF over the course of one year. As shown in Figure 6, the change in Net UF over one year (ΔNetUF) and the baseline autotaxin concentration, which is the measurement value at the first mini-PET since the start of observation, showed a tendency to correlate with the autotaxin concentration in the first year and the change in Net UF over one year, with a correlation coefficient of r = -0.353 and a significant difference of p = 0.141. It is also suggested that by increasing the number of cases in the future, it may become a predictive marker for water removal ability.

[0055] As is clear from these analyses 1 to 5, the autotaxin concentration in peritoneal dialysis effluent correlated with D / P Cr and D / D0Glu in the conventionally widely used PET test, as well as with dip Na, which has been suggested to be associated with water removal failure in previous reports. In addition, the autotaxin concentration in the first year tended to correlate with the change in net UF over the course of one year. These results indicate that autotaxin in peritoneal dialysis effluent reflects peritoneal function and is useful as a simple and easy-to-use marker for evaluating peritoneal function in place of D / P Cr and D / D0Glu in PET tests. [Industrial Applicability]

[0056] According to the method for evaluating and determining peritoneal function of the present invention, peritoneal dialysis is selected from peritoneal dialysis and hemodialysis at the beginning of artificial dialysis, and a peritoneal function evaluation marker consisting of autotaxin in the drainage peritoneal dialysis fluid is measured as an indicator for periodic testing to prolong the function of the peritoneum as much as possible, and appropriate peritoneal function evaluation is performed, which can be used to expand peritoneal dialysis and continue peritoneal dialysis for a long time. Furthermore, if insurance coverage for measuring autotaxin in evaluating peritoneal function is approved, the number of orders for testing will increase, reducing medical resources for hemodialysis and improving the medical economy.

Claims

1. A marker for evaluating peritoneal function, characterized in that it consists of autotaxin.

2. The peritoneal function evaluation marker according to claim 1, characterized in that the autotaxin is present in peritoneal dialysis effluent.

3. The peritoneal function evaluation marker according to any one of claims 1 to 2, characterized in that it is used to evaluate at least one indicator selected from the possibility of continuing peritoneal dialysis and the predictability of transition to hemodialysis.

4. The peritoneal function evaluation marker according to claim 3, characterized in that the threshold value of the indicator is more than 1.5 ng / ml.

5. A kit for evaluating peritoneal function, comprising a reagent for detecting a peritoneal function evaluation marker consisting of autotaxin.

6. The kit for evaluating peritoneal function according to claim 5, characterized in that the reagent contains an anti-autotaxin monoclonal antibody and an enzyme-labeled reagent of the anti-autotaxin monoclonal antibody.

7. A method for measuring peritoneal dialysis effluent, comprising detecting a peritoneal function evaluation marker consisting of autotaxin in the peritoneal dialysis effluent.

8. The method for measuring peritoneal dialysis effluent according to claim 7, characterized in that the peritoneal function evaluation marker is at least one indicator selected from the group consisting of the possibility of continuing peritoneal dialysis and the predictability of transition to hemodialysis.

9. The method for measuring peritoneal dialysis effluent according to claim 7, characterized in that the peritoneal function evaluation marker is measured using an anti-autotaxin monoclonal antibody and an enzyme-labeled reagent of the anti-autotaxin monoclonal antibody.

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