KR102012899B1 - Diagnostic strategy and tool for successful weaning from renal replacement therapy after acute kidney injury - Google Patents

Abstract

The present invention relates to the field of treatment of kidney disease. More specifically, the method of deciding when to stop renal replacement therapy, in particular, when acute kidney injury is performed by renal replacement therapy such as hemodialysis, The present invention relates to a method for determining when to stop renal replacement therapy and a diagnostic kit for determining when to stop.

Description

Diagnostic strategy and tool for successful weaning from renal replacement therapy after acute kidney injury}

The present invention relates to the field of treatment of kidney disease. More specifically, the method of deciding when to stop renal replacement therapy, in particular, when acute kidney injury is performed by renal replacement therapy such as hemodialysis, The present invention relates to a method for determining when to stop renal replacement therapy and a diagnostic kit for determining when to stop.

The kidney is an important organ that maintains homeostasis of the living body, which regulates the amount of fluid in the body, ion concentration and pH in the blood, excretes metabolic wastes, toxins, and drugs, and controls blood pressure and other metabolic and endocrine functions. To perform. It also activates vitamin D, helping to absorb calcium from the small intestine and is involved in the synthesis of several hormones.

Kidney disease is a condition in which the kidneys fail to excrete, regulate, metabolize, and endocrine functions normally, and the function of the kidneys is reduced or abnormal. Degradation of function due to kidney damage results in increased kidneys and related structures, kidney atrophy, changes in fluid volume, electrolyte imbalance, metabolic acidosis, gas exchange disorders, impaired anti-infective function, and accumulation of urinary toxins.

Acute kidney injury is a common complication in patients admitted to hospitals or intensive care units. Recent cross-sectional studies have reported acute renal impairment in half of patients admitted to the intensive care unit, which has been shown to be closely associated with deterioration of renal function and increased mortality. Severe acute kidney injury results in loss of renal function and therefore requires replacement of the kidney.

Although some observational studies and a few randomized controlled trials have investigated the timing of continuous kidney replacement, including adequate hemodialysis, when kidney damage occurs in hospitalized patients, kidney replacement therapy is still present. Contrary to the results, it is better to start early or start later. Furthermore, few studies have been conducted on the diagnosis and prediction of the appropriate time to stop the renal replacement therapy in patients with acute kidney injury.

In a previous study, the urine volume of a patient was reported as a predictor of the decision to stop renal replacement therapy, but the use of diuretics to increase urine volume was not predictable for successful discontinuation of renal replacement therapy.

Therefore, methods needed to more accurately determine when to stop renal replacement therapy need to be developed.

The present inventors have a variety of side effects such as organ damage and catheter infection due to hemodynamic insufficiency when a patient receiving kidney replacement therapy after acute kidney injury does not know when the kidney is recovered and continues to receive kidney replacement therapy. As a result of research efforts to develop a predictive method for determining the necessity of stopping renal replacement therapy, it was confirmed that renal replacement therapy can be stopped when a certain element in the blood of the patient is above a certain value, thereby completing the present invention.

Thus, an object of the present invention is to provide kidney biomarkers with kidney disease resulting from acute kidney injury using at least one of the concentration of cystatin C in the blood and the glomerular filtration rate calculated based on the concentration as a biomarker to determine the appropriate time to stop renal replacement therapy. It provides a method of determining when to discontinue alternative therapy and a diagnostic kit.

The objects of the present invention are not limited to the above-mentioned objects, and other objects that are not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object of the present invention, the present invention provides a biological fluid sample obtained from a patient undergoing kidney replacement therapy for acute kidney injury; Measuring a cystatin C value in the provided fluid sample; And determining when to stop renal replacement therapy in the patient based on the measured cystatin C value.

The present invention also provides a biological fluid sample obtained from a patient undergoing kidney replacement therapy for acute kidney injury; Measuring a cystatin C value in the provided fluid sample; Calculating glomerular filtration rate values using the measured cystatin C values; And determining when to stop renal replacement therapy of the patient based on the cystatin C value and the glomerular filtration rate value.

In a preferred embodiment, the determination comprises correlating at least one of the cystatin C value and the glomerular filtration rate value with a set value.

In a preferred embodiment, the set value for the cystatin C value is less than 1.85 mg / L.

In a preferred embodiment, the set value for the glomerular filtration rate value is at least 32.9 ml / min / 1.73 m ² .

In a preferred embodiment, the biological fluid sample is any one of blood, serum, and plasma.

The present invention also provides a diagnostic kit for use in determining when to stop renal replacement therapy in a patient undergoing renal replacement therapy for acute kidney injury, comprising: means for detecting cystatin C concentration in a biological fluid sample obtained from the patient; It provides a diagnostic kit comprising; and means for measuring the detected cystatin C concentration.

In a preferred embodiment, means for calculating the glomerular filtration rate using the measured cystatin C concentration further comprises.

In a preferred embodiment, the biological fluid sample is any one of blood, serum, and plasma.

According to the present invention, renal replacement therapy due to acute kidney injury is stopped by using one or more of the concentration of cystatin C in the blood of a patient undergoing kidney replacement therapy after acute kidney injury and the glomerular filtration rate calculated based on the concentration as a biomarker. The timing can be predicted successfully.

The effects of the present invention are not limited to the above-mentioned effects, and other effects that are not mentioned will be clearly understood by those skilled in the art from the following description.

Figures 1a to 1c is a comparison of the group that was successfully stopped at the time of discontinuation after renal replacement therapy after acute kidney injury and failed group of serum NGAL (A), cystatin C (B), urine volume (C), respectively The graph shows the change as a scatter dot plot.
FIG. 2A is a graph showing the results of a receiver-operating characteristic curve (ROC) analysis of glomerular filtration rate using cystatin C as a diagnostic biomarker in connection with the successful discontinuation of renal replacement therapy. FIG. A graph showing the receiver-operating characteristic curve (ROC) analysis of glomerular filtration rate using sastatin C.

The terms used in the present invention were selected as general terms as widely used as possible, but in some cases, the terms arbitrarily selected by the applicant are included. In this case, the meanings described or used in the detailed description of the present invention are considered, rather than simply the names of the terms. The meaning should be grasped.

Hereinafter, with reference to the accompanying drawings and preferred embodiments will be described in detail the technical configuration of the present invention.

However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Like reference numerals used to describe the present invention throughout the specification denote like elements.

Technical feature of the present invention is the kidney replacement due to acute kidney injury by using at least one of the concentration of cystatin C in the blood of patients undergoing kidney replacement therapy after acute kidney injury and the glomerular filtration rate calculated based on the concentration as a biomarker. Methods of determining when to discontinue the therapy can be predicted successfully and the diagnostic kit used for the method.

Here, cystatin C is a protein produced in all cells as a cysteine protease inhibitor. Serum cystatin C produced in normal humans is almost completely reabsorbed and metabolized in the proximal tubules, so cystatin C is rarely detected in urine. To date, known studies have suggested that cystatin C in serum is a superior marker for serum creatinine in assessing glomerular filtration rate. It also has a shorter half-life than creatinine, which is considered to be a better biomarker for predicting acute kidney injury. However, there are limitations in predicting acute kidney injury, necessity of renal replacement therapy, and mortality in intensive care units and inpatients. As described above, in case of continuous renal replacement therapy including hemodialysis in inpatients with acute kidney injury, there are few studies on new biomarkers including cystatin C as a factor for predicting and diagnosing successful discontinuation. to be.

Therefore, the method of determining when to stop renal replacement therapy due to acute kidney injury of the present invention is to provide a biological fluid sample obtained from a patient who is undergoing kidney replacement therapy for acute kidney injury by using cystatin C as a biomarker. ; Measuring a cystatin C value in the provided fluid sample; And determining when to stop renal replacement therapy in the patient based on the measured cystatin C value.

If necessary, the method of determining when to stop renal replacement therapy due to acute kidney injury comprises the steps of providing a biological fluid sample obtained from a patient undergoing renal replacement therapy for acute kidney injury; Measuring a cystatin C value in the provided fluid sample; Calculating glomerular filtration rate values using the measured cystatin C values; And determining when to stop the renal replacement therapy of the patient based on the cystatin C value and the glomerular filtration rate value.

Here, the biological fluid sample may be any one of blood, serum, and plasma, and the determination of when to stop the renal replacement therapy of the patient correlates one or more of the cystatin C value and the glomerular filtration rate value with the respective set values. Including, the setting value for the cystatin C value is less than 1.85 mg / L, the setting value for the glomerular filtration rate value is 32.9ml / min / 1.73m ² or more. That is, at least one of the measured cystatin C value is less than or equal to the preset value of 1.85 mg / L or the calculated glomerular filtration rate value is greater than or equal to the preset value of 32.9 ml / min / 1.73 m ^2. This is because if one of the patient's kidney replacement therapy can be stopped. In particular, if the measured cystatin C value and glomerular filtration rate value correspond to two preset values, the most accurate judgment is possible, but only the cystatin C value can be used to obtain valid accuracy.

Next, the diagnostic kit of the present invention is a diagnostic kit for determining when to stop renal replacement therapy in patients undergoing renal replacement therapy due to acute kidney injury, and detects cystatin C concentration in a biological fluid sample obtained from the patient. Detecting means; And measuring means for measuring the detected cystatin C concentration. If necessary, the calculation means for calculating the glomerular filtration rate using the measured cystatin C concentration may further include.

In one embodiment, the diagnostic kit may comprise reagents for detecting and measuring cystatin C in a sample and specific antibodies to cystatin C. The sample can be a bodily fluid such as blood, serum, plasma. In another embodiment, the diagnostic kit may include an immobilized antibody that specifically recognizes cystatin C and an antibody that is capable of binding antigen components specific to cystatin C and other than the immobilized antibody. In this case, the cystatin C antibody may be enzyme-labeled, radio-labeled or fluorescently-labeled.

The diagnostic kit may further comprise reagents necessary for detecting the antibody, and other reagents, such as, for example, solubilizers, cleaners and reaction terminators, if necessary, include the essential components of the diagnostic kit, and It may be packaged in a box or container containing the relevant instructions.

The diagnostic kit may also be used in conjunction with a software program that can quantitatively measure cystatin C concentration in a sample, for example, by image analysis or other comparative techniques.

Unless otherwise specified, the examples were performed based on the following subject groups and experimental methods.

1. Target group

Patients who were admitted to the intensive care unit who needed continuous renal replacement therapy due to acute kidney injury were included. Younger than 18 years of these patients; Patients who cannot stop renal replacement after renal replacement because their renal function has not recovered; Patients who have undergone hemodialysis or peritoneal dialysis due to terminal renal failure before hospitalization; Patients who died during or after continuous renal replacement therapy within 12 hours; When discontinued by a patient caregiver; Pregnant women or women of childbearing age were excluded from this study. As a result, a total of 110 patients were enrolled in the study and analyzed. All patients were followed up until their discharge or hospital death. All patients were informed of the study prior to participation in the clinical study and informed consent was submitted. The clinical trial was reviewed and approved by the Institutional Review Board of Chonnam National University Hospital.

2. Data Collection and Definition

Patient information and laboratory results were collected from patient electronic charts. age; gender; body mass index; History of hypertension, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, smoking status; Mode at the start of continuous renal replacement therapy; The use of diuretics and boosters; Test values of blood urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), cystatin C; Urine volume at the start or stop of continuous renal replacement therapy was collected. Simplified Acute Physiology Score (SAPS) III was calculated to provide a risk of death. Cystatin C and NGAL were evaluated by IFCC and enzyme-linked immunosorbent assay.

Glomerular filtration rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. Glomerular filtration rate calculated by cystatin C alone or in combination with cystatin C and creatinine was estimated using CKD-EPI cystatin C formula and CKD-EPI creatinine-cistatin C formula.

Successful discontinuation in continuous renal replacement therapy was defined as no longer requiring renal replacement therapy for at least 14 days after discontinuation of dialysis, whereas renal replacement therapy was performed within 14 days of discontinuation of renal replacement therapy. Renal replacement therapy was defined and based on previous studies.

3. Statistical Analysis

Patient severity and laboratory data were expressed as mean with standard distribution, mean with standard deviation, and median and quartile (25 ^th and 75 ^th percentiles) when not following normal distribution. Categorical variables are expressed in numbers and percentages, respectively. Comparisons between the two groups were made using Student's t-test, Mann-Whitney test, Pearson chi-square, and Fisher exact test. In order to find the appropriate limit value for continuous renal replacement therapy, the area under the receiver-operating characteristic curve (AUC) was drawn using the ROC curve, and Euclidean distance and Youden index methods were used. Multivariate logical regression analysis was used to analyze biomarkers and clinical factors associated with the successful discontinuation of continuous renal replacement therapy. The Cox proportional hazard analysis method was used to analyze the independent association between successful discontinuation of renal replacement therapy and patient death in the hospital. All statistical analyzes defined that there were statistical significances when the two-sided test and P-value were less than 0.05. All analyzes used Statistical Package for Social Sciences software, version 21.0.

Example

1. Basic patient data in the experiment

After measuring the test values for the existing patient information and clinical results, the successful renal replacement therapy was successfully divided into the discontinued group and the failed restart-continuous renal replacement group shown in Tables 1 to 3 and FIGS. 1A to 1C.

As shown in Tables 1 to 3, 89 (80.9%) of 110 patients successfully discontinued continuous renal replacement, and 21 (19.1%) patients did not successfully discontinue continuous renal replacement. Failed patient group had higher hypertension rate than successful patient group, and daily furosemide consumption was higher than successful patient group for 24 hours before stopping continuous renal replacement therapy. The mode of continuous renal replacement therapy, the SAPS III scores, etc. showed no significant difference between the two groups.

Total (n = 110) Successfully weaned (n = 89) Restarted RRT (n = 21) P value Age (year) 63.2 ± 14.6 62.6 ± 15.2 65.5 ± 12.1 0.419 Male (%) 69 (62.7) 55 (61.8) 14 (66.7) 0.678 Systolic BP (mmHg) 121 ± 29 120 ± 26 126 ± 37 0.421 Diastolic BP (mmHg) 64 ± 21 62 ± 17 71 ± 32 0.079 Current / former Smoker (%) 52 (46.3) 41 (46.1) 11 (52.4) 0.730 BMI (kg / m ² ) 23.5 ± 4.4 23.3 ± 4.3 24.3 ± 4.9 0.368 Diabetes (%) 55 (50.0) 41 (46.1) 14 (66.7) 0.089 Hypertension (%) 65 (59.1) 48 (53.9) 17 (81.0) 0.027 COPD (%) 8 (7.3) 7 (7.9) 1 (4.8) 1.000 Sepsis / septic shock (%) 41 (37.3) 30 (33.7) 11 (52.4) 0.111 SAPS III score 58.1 ± 16.2 56.9 ± 15.8 63.2 ± 17.1 0.107 SAPS III death rate,% 35.0 ± 23.5 33.0 ± 23.3 43.0 ± 23.3 0.081 Setting of CRRT Blood flow rate, mL / hr (IQR) 150 (150, 150) 150 (130, 150) 150 (150, 150) 0.188 Dialysate flow rate, mL / hr (IQR) 1200 (1000, 1325) 1100 (1000, 1350) 1200 (1050, 1325) 0.583 Replacement flow rate, mL / hr (IQR) 1200 (1000, 1400) 1100 (1000, 1400) 1200 (1000, 1325) 0.744 Ultrafiltration rate, mL / hr (IQR) 50 (0, 100) 50 (0, 100) 50 (0, 100) 0.897

Total (n = 110) Successfully weaned (n = 89) Restarted RRT (n = 21) P value Vasopressors / inotropes ^a Dopamine (%) 33 (30.0) 24 (27.0) 9 (42.9) 0.153 Dopamine, μg / min / kg (IQR) 0 (0, 4.2) 0 (0, 3.0) 0 (0, 5.5) 0.291 Norepinephrine (%) 60 (54.5) 47 (52.8) 13 (61.9) 0.451 Norepinephrine, μg / min / kg (IQR) 0.09 (0,0.46) 0.07 (0, 0.46) 0.20 (0,0.47) 0.489 Dobutamine (%) 6 (5.5) 5 (5.6) 1 (4.8) 1.000 Dobutamine, μg / min / kg (IQR) 0 (0, 0) 0 (0, 0) 0 (0, 0) 0.900 Furosemide (%) 74 (67.3) 56 (62.9) 18 (85.7) 0.068 Intravenous furosemide, mg / day (IQR) 40 (0,153) 40 (0, 120) 60 (20, 230) 0.045 Furosemide (%) ^b 43 (39.1) 32 (36.0) 11 (52.4) 0.165 Intravenous furosemide, mg / day (IQR) ^b 0 (0, 40) 0 (0, 30) 20 (0, 50) 0.289

^a At initiation of CRRT.

^b 24h before CRRT cessation.

Total (n = 110) Successfully weaned (n = 89) Restarted RRT (n = 21) P value At CRRT discontinuation BUN (mg / dL) 22.1 ± 13.5 20.8 ± 10.3 27.3 ± 21.4 0.169 Creatinine (mg / dL) 1.3 ± 1.0 1.2 ± 0.9 1.5 ± 1.3 0.147 Serum NGAL (ng / mL) 584.7 ± 389.9 555.5 ± 389.9 726.8 ± 368.6 0.099 Serum CysC (mg / L) 1.85 ± 0.79 1.70 ± 0.68 2.47 ± 0.93 <0.001 eGFR ^c 69.5 ± 32.4 72.1 ± 32.6 58.4 ± 29.9 0.082 eGFRcreatinine-CysC ^d 52.2 ± 29.4 55.5 ± 30.3 38.1 ± 20.5 0.014 eGFR CysC ^e 44.1 ± 28.5 47.9 ± 29.6 27.6 ± 14.9 <0.001 U / O, ml / hr / kg (IQR) 1.23 (0.61, 2.27) 1.33 (0.67, 2.56) 0.78 (0.27, 1.42) 0.016 Clinical outcomes CRRT duration, day (IQR) 3.0 (3.0, 5.0) 3.0 (3.0, 5.0) 4.0 (3.0, 6.0) 0.136 ICU stay, day (IQR) 10.0 (6.0, 22.0) 9.0 (5.5, 18.5) 20.0 (8.5, 33.0) 0.004 Hospital stay, day (IQR) 21.0 (14.0, 38.3) 19.0 (14, 38.5) 27.0 (20.5, 39.5) 0.149 In-hospital mortality (%) 26 (23.6) 13 (14.6) 13 (61.9) <0.001

^c eGFR is given in ml / min per 1.73 m ² , calculatedusingtheCKD-EPIequation.

^d eGFR is given in ml / min per 1.73 m ² , calculatedusingtheCKD-EPIcreatinine-cystatinCequation.

^e eGFR is given in ml / min per 1.73 m ² , calculatedusingtheCKD-EPIcystatinCequation.

Abbreviations: BP, blood pressure; BMI, body mass index; COPD, chronic obstructive pulmonary disease; SAPS; Simplified Acute Physiology Score; CRRT, continuous renal replacement therapy; IQR, interquartile range; BUN, blood urea nitrogen; NGAL, neutrophil gelatinase-associated lipocalin; CysC, cystatin C; eGFR, estimated glomerular filtration rate; U / O, urine output; ICU, intensive care unit.

As shown in Tables 1 to 3, the comparison of the various biomarkers and urine volume at the time of discontinuation of renal replacement therapy in the successful and failed groups was not statistically significant, but the serum creatinine and NGAL values were more successful than the failed group. Low values in group (serum creatinine: 1.2 ± 0.9 mg / dL vs. 1.5 ± 1.3 mg / dL, P = 0.147; NGAL: 556 ± 390 ng / mL vs. 727 ± 369 ng / mL, P = 0.099) . Serum cystatin C, however, was significantly lower in the group that successfully discontinued persistent renal replacement, whereas the urine volume was higher (cystatin C: 1.70 ± 0.68 mg / L vs. 2.47). ± 0.93 mg / L, P <0.001; urine volume: 1.33 [0.67, 2.56] mL / h / kg vs. 0.78 [0.27, 1.42] mL / h / kg, P = 0.016) (FIGS. 1A and 1B). In addition, the glomerular filtration rate using cystatin C alone and the glomerular filtration rate using both creatinine and cystatin C were significantly higher in the successful group than in the failed group, whereas the glomerular filtration rate using creatinine was significantly different between the two groups. Did not look.

2. Analysis of Predictors of Successful Continuous Renal Replacement Therapy

ROC curve analysis was performed to evaluate the limit values of glomerular filtration rate with various biomarkers, clinical variables, and cystatin C, and to evaluate the predictive accuracy of successful continuous renal replacement therapy. And shown in FIGS. 2A and 2B.

AUC SE 95% CI P value eGFR CysC ^{a, d} 0.746 0.059 0.631-0.861 <0.001 Serum CysC (mg / dL) 0.739 0.059 0.614-0.853 0.001 eGFR creatinine-CysC ^{a, c} 0.681 0.066 0.551-0.810 0.010 Urine output (ml / hr / kg) ^a 0.669 0.062 0.547-0.792 0.016 Serum NGAL (ng / mL) ^a 0.640 0.066 0.512-0.768 0.070 eGFR ^{a, b} 0.612 0.070 0.475-0.749 0.111 Creatinine (mg / dL) 0.601 0.074 0.455-0.747 0.151

^a At the time of weaning from CRRT

^b eGFR is given in ml / min per 1.73 m ² , calculatedusing the CKD-EPIequation.

^c eGFR is given in ml / min per 1.73 m ² , calculatedusingtheCKD-EPIcreatinine-cystatinCequation.

^d eGFR is given in ml / min per 1.73 m ² , calculatedusingtheCKD-EPIcystatinCequation.

Abbreviations: AUC, area under the receiver opening characteristic curve; CRRT, continuous renal replacement therapy; SE, standard error; CI, confidence interval; eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CysC, cystatin C; NGAL, neutrophil gelatinase-associated lipocalin

The glomerular filtration rate with serum cystatin C and cystatin C alone and the glomerular filtration rate with both creatinine and cystatin C were statistically significant predictors of successful discontinuation of renal replacement therapy. The glomerular filtration rate using cystatin C alone showed the highest AUC of 0.746 (95% confidence interval [CI], 0.631-0.861, P <0.001), with sensitivity and specificity of 62.5% and 76.2%, respectively. Showed. The limit value was 32.9 mL / min / 1.73 m ² . Cystatin C had an AUC of 0.739 and a limit of 1.85 mg / L with sensitivity and specificity of 76.2% and 62.9%, respectively. ROC curves are represented in FIGS. 2A and 2B.

Through multivariate logical regression analysis, glomerular filtration rate using cystatin C was analyzed as an independent factor predicting successful discontinuation of renal replacement therapy, and the results are shown in Tables 5 to 7 (odds ratio, 1.056; 95). % CI, 1.008-1.107; P = 0.022).

However, as shown in Tables 5 to 7, creatinine alone or glomerular filtration rate using creatinine and cystatin C, NGAL (neutrophil gelatinase-associated lipocalin) and urine volume at the end of continuous renal replacement therapy were not associated with successful discontinuation. .

Univariate Model 1 (R ² = 0.186) Odds ratio (95% CI) P value Odds ratio (95% CI) P value Age 0.986 (0.952-1.020) 0.417 1.017 (0.970-1.067) 0.481 Male 0.809 (0.297-2.205) 0.678 0.762 (0.217-2.671) 0.671 Hypertension 0.275 (0.086-0.884) 0.030 0.317 (0.075-1.334) 0.117 Use of furosemide ^a 0.510 (0.195-1.322) 0.169 0.488 (0.145-1.638) 0.246 BUN (mg / dL) ^a 0.968 (0.937-1.000) 0.048 1.001 (0.944-1.062) 0.961 NGAL (ng / mL) ^a 0.999 (0.998-1.000) 0.103 1.000 (0.998-1.001) 0.538 Urine output (ml / hr / kg) ^a 1.714 (1.031-2.849) 0.038 1.566 (0.935-2.621) 0.088 SAPS III score 0.975 (0.946-1.006) 0.109 0.989 (0.956-1.024) 0.544 eGFR ^{a, b} 1.015 (0.998-1.032) 0.084 1.002 (0.976-1.029) 0.853 eGFR creatinine-CysC ^{a, c} 1.033 (1.006-1.061) 0.018 - eGFR CysC ^{a, d} 1.057 (1.017-1.098) 0.005 -

Univariate Model 2 (R ² = 0.220) Odds ratio (95% CI) P value Odds ratio (95% CI) P value Age 0.986 (0.952-1.020) 0.417 1.024 (0.974-1.076) 0.354 Male 0.809 (0.297-2.205) 0.678 0.710 (0.203-2.488) 0.593 Hypertension 0.275 (0.086-0.884) 0.030 0.330 (0.080-1.368) 0.126 Use of furosemide ^a 0.510 (0.195-1.322) 0.169 0.527 (0.161-1.729) 0.291 BUN (mg / dL) ^a 0.968 (0.937-1.000) 0.048 1.020 (0.964-1.080) 0.487 NGAL (ng / mL) ^a 0.999 (0.998-1.000) 0.103 1.000 (0.998-1.001) 0.792 Urine output (ml / hr / kg) ^a 1.714 (1.031-2.849) 0.038 1.484 (0.903-2.438) 0.119 SAPS III score 0.975 (0.946-1.006) 0.109 0.989 (0.990-1.065) 0.529 eGFR ^{a, b} 1.015 (0.998-1.032) 0.084 - eGFR creatinine-CysC ^{a, c} 1.033 (1.006-1.061) 0.018 1.027 (0.990-1.065) 0.155 eGFR CysC ^{a, d} 1.057 (1.017-1.098) 0.005 -

Univariate Model 3 (R ² = 0.293) Odds ratio (95% CI) P value Odds ratio (95% CI) P value Age 0.986 (0.952-1.020) 0.417 1.036 (0.983-1.092) 0.181 Male 0.809 (0.297-2.205) 0.678 0.579 (0.164-2.174) 0.434 Hypertension 0.275 (0.086-0.884) 0.030 0.285 (0.057-1.165) 0.078 Use of furosemide ^a 0.510 (0.195-1.322) 0.169 0.536 (0.157-1.832) 0.320 BUN (mg / dL) ^a 0.968 (0.937-1.000) 0.048 1.027 (0.971-1.087) 0.352 NGAL (ng / mL) ^a 0.999 (0.998-1.000) 0.103 1.000 (0.998-1.002) 0.937 Urine output (ml / hr / kg) ^a 1.714 (1.031-2.849) 0.038 1.437 (0.885-2.334) 0.142 SAPS III score 0.975 (0.946-1.006) 0.109 0.990 (0.956-1.026) 0.594 eGFR ^{a, b} 1.015 (0.998-1.032) 0.084 - eGFR creatinine-CysC ^{a, c} 1.033 (1.006-1.061) 0.018 - eGFR CysC ^{a, d} 1.057 (1.017-1.098) 0.005 1.056 (1.008-1.107) 0.022

3. Analysis of clinical results

The results of the analysis of the clinical results are listed in Tables 1 to 3 above. Successful discontinuation of continuous renal replacement therapy showed lower in-hospital mortality and shorter ICU admissions than failure (in-hospital mortality: 14.6% vs. 61.9%, P <0.001; ICU admission period: 9.0 [5.5 , 18.5] day vs. 20.0 [8.5, 33.0] day, P = 0.004, respectively). However, there was no statistically significant difference in the duration or duration of hospitalization between the two groups. Furthermore, referring to Table 8, which shows the results of the Cox proportional risk analysis method, patients who successfully stopped continuous renal replacement were associated with lower hospital deaths compared to those who failed. (hazard ratio, 0.286; 95% CI, 0.116-0.708; P = 0.007)

Unadjusted P  value Model 1 ^a P  value Model 2 ^b P  value Restart-RRT group Reference Reference Reference Success weaning group 0.105 (0.037-0.304) <0.001 0.240 (0.106-0.542) 0.001 0.286 (0.116-0.708) 0.007

^a Model 1, adjusted for age and sex.

^b Model 2, adjusted for Model 1 plus hypertension, diabetes mellitus, chronic obstructive pulmonary disease, liver disease, heart failure, cerebral vascular disease, urine output, SAPS III score.

Abbreviations: CRRT, continuous renal replacement therapy; RRT, renal replacement therapy.

From the above results, it can be seen that by measuring the cystatin C in patients undergoing renal replacement therapy using the present invention, it is possible to accurately determine when it is possible to successfully stop renal replacement therapy. Therefore, the diagnostic kit of the present invention can be usefully used to predict the time of successful discontinuation in patients undergoing renal replacement therapy in patients admitted with acute kidney injury.

Although the present invention has been shown and described with reference to the preferred embodiments as described above, it is not limited to the above embodiments and those skilled in the art without departing from the spirit of the present invention. Various changes and modifications will be possible.

Claims (9)

Providing a biological fluid sample obtained from a patient undergoing kidney replacement therapy with acute kidney injury;
Measuring a cystatin C value in the provided fluid sample; And
Determining when to stop renal replacement therapy of the patient based on the measured cystatin C value;
The determination comprises correlating the measured cystatin C value with a set value, and determining that the patient will stop renal replacement therapy if the measured cystatin C value is less than or equal to the set value of 1.85 mg / L. How to determine when to stop renal replacement therapy due to acute kidney injury.
Providing a biological fluid sample obtained from a patient undergoing kidney replacement therapy with acute kidney injury;
Measuring a cystatin C value in the provided fluid sample;
Calculating glomerular filtration rate values using the measured cystatin C values; And
Determining when to stop renal replacement therapy in the patient based on the measured cystatin C value and the calculated glomerular filtration rate value.
The determination comprises correlating one or more of the measured cystatin C value and the calculated glomerular filtration rate value with each set value,
The kidney replacement of the patient when the measured cystatin C value corresponds to at least one of the conditions of the set value of 1.85 mg / L or less and the calculated glomerular filtration rate value of the set value of 32.9 ml / min / 1.73 m ² or more. A method for determining when to stop renal replacement therapy due to acute kidney injury, characterized in that it is determined to discontinue therapy.
delete delete delete The method according to claim 1 or 2,
The biological fluid sample is blood, serum, plasma, characterized in that any one of the renal replacement therapy stop time determination due to acute kidney injury.
A diagnostic kit for determining when to stop renal replacement therapy in patients undergoing renal replacement therapy for acute kidney injury.
Means for detecting cystatin C concentration in a biological fluid sample obtained from said patient; And
And means for measuring the detected cystatin C concentration.
If the measured cystatin C value is less than the predetermined value of 1.85 mg / L diagnostic kit, characterized in that to stop the kidney replacement therapy of the patient.
A diagnostic kit for determining when to stop renal replacement therapy in patients undergoing renal replacement therapy for acute kidney injury.
Means for detecting cystatin C concentration in a biological fluid sample obtained from said patient;
Means for measuring the detected cystatin C concentration; And
Means for calculating glomerular filtration rate using the measured cystatin C concentration.
The height of the patient if the measured cystatin C value is at least one of the conditions of 1.85 mg / L or less, and the measured glomerular filtration rate is 32.9 ml / min / 1.73 m ² or more. A diagnostic kit, characterized in that to stop the alternative therapy.
The method according to claim 7 or 8,
The biological fluid sample is a diagnostic kit, characterized in that any one of blood, serum, plasma.

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