The predictive value of urinary kidney injury molecular-1 for long-term graft function in kidney transplant patients: a prospective study
Minyan ZhuZhejun ChenYuehan WeiYanhong YuanYing LiangHang ZhouXiajing CheMin Fang ZhangZhaohui NiMing ZhangShan Mou
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Monitoring allograft function during the early stages is crucial, and therefore requires biomarkers more sensitive than serum creatinine (Scr). Kidney injury molecular-1 (KIM-1) is a potent biomarker; however, disparities exist in the literature concerning its predictive value in allograft function. Therefore, this study aimed to evaluate its predictive value for the long-term prognosis of kidney transplantation patients.A prospective study with a cohort comprising 160 patients scheduled for kidney transplantation was conducted to evaluate the predictive power of urinary KIM-1 (uKIM-1) and other renal ischemia-reperfusion biomarkers including urinary L-type fatty acid binding protein (uL-FABP), urinary N-acetyl-β-D glucosaminidase (uNAG), and urinary neutrophil gelatinase-related lipoprotein (uNGAL) for allograft prognosis.One hundred and forty kidney recipients who were admitted to our hospital between September 2014 and December 2017 with a median follow-up of 30.3 months were included. Thirty-seven recipients had functional delayed graft function (fDGF) in the first week post transplantation, and 42 recipients had progressed to allograft dysfunction [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] by the end of the study, while nine recipients deteriorated into allograft loss (defined by the initiation of dialysis). The levels of uKIM-1 in the fDGF group were higher than those in the immediate graft function (IGF) recipients (P<0.05) at 0 hour post transplantation [5.885 (4.420-7.913) vs. 4.605 (3.417-5.653) ng/mmol], and on the first day post transplantation [5.569 (4.181-6.722) vs. 4.002 (3.222-6.488) ng/mmol]. The levels of uL-FABP in the fDGF group were also higher than those in the IGF group at 0 hour post transplantation (89.818±39.332 vs. 69.187±37.926 µg/mmol) and on the third day post transplantation [77.835 (60.368-100.678) vs. 66.841 (28.815-89.783) µg/mmol]. Multivariate Cox regression analysis demonstrated that recipients with higher uKIM-1 levels on the first day post transplantation had a 23.5% increase in the risk of developing fDGF and a 27.3% increase in the risk of prolonged renal allograft dysfunction.uKIM-1 on the first day post transplantation can predict short-term graft function and is a potent biomarker for the long-term prognosis of graft function.To compare the conventional creatinine clearance measured on 24-h urine collection with the estimated Glomerular Filtration Rate by Cockcroft & Gault (CG) and Modification of Diet in Renal Disease (MDRD) prediction equations in adults aged 20 years and above in Pakistani population.All the patients, including inpatient admitted in hospital and outpatients, more than 20 years of age, reporting for the test of creatinine clearance in clinical chemistry department of Dr. Ziauddin Hospital clinical laboratory from 1st January to 31st December 2006 were studied.Comparison was made between conventional creatinine clearance and Cockcroft & Gault (CG) and Modification of Diet in Renal Disease (MDRD) prediction equations on 369 cases which revealed strong correlation with conventional creatinine clearance, MDRD equation has better correlation as compared with Cockcroft- Gault creatinine clearance. Statistical correlation was better in cases where serum creatinine was more than 1.50 mg/dl (r = 0.625 for Cockcroft- Gault creatinine clearance and r = 0.724 for MDRD equation) as compared when serum creatinine levels were less than 1.50 mg/dl (r = 0.608 for Cockcroft- Gault creatinine clearance and r = 0.596 for MDRD equation). There was positive bias in both calculated GFRs from conventional creatinine clearance in healthy as well as diseased population.The creatinine based formulas with their inherent property of convenience and cost effectiveness can be a useful tool for monitoring the progression of disease. They can be applied in clinical practice on our population but they should be interpreted with caution as they over estimate the GFR.
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We evaluated cystatin C concentration as a marker of glomerular filtration rate in renal transplant recipients, and its correlation with creatinine-based glomerular filtration rate by urinary creatinine clearance, and the Cockroft-Gault and Modification of Diet in Renal Disease formulas.In this cross-sectional study, we measured serum cystatin C levels and its correlation with serum creatinine, creatinine clearance, and glomerular filtration rate using the Cockroft-Gault formula and Modification of Diet in Renal Disease formulas.One hundred two recipients between June and December 2012, were examined. The mean subject age was 31.87 ± 8.37 years; the male:female ratio was 4.3:1. Mean serum creatinine concentration was 141.44 ± 43.31 mol/L (1.60 ± 0.49 mg/dL) and serum cystatin C 122.09 ± 38.95 nmol/L (1.63 ± 0.52 mg/L). Serum cystatin C was significantly correlated with serum creatinine (r=0.90; P<.001), creatinine clearance (r=0.77; P<.001), and the Cockroft-Gault (r=0.73; P<.001) and the Modification of Diet in Renal Disease formulas (r=0.82; P<.001). We assessed the correlation among serum cystatin C with serum creatinine, creatinine clearance, the Cockroft-Gault and Modification of Diet in Renal Disease at 1, 2-3, 4-5, and more than 5 years after transplant. The correlation between serum cystatin C and serum creatinine ranged from 0.8 to 1.0; cystatin C and creatinine clearance ranged from 0.8 to 0.85; serum cystatin C and the Cockroft-Gault Formula ranged from 0.7 to 0.8; and serum cystatin C and the Modification of Diet in Renal Disease formulas ranged from 0.8 to 0.84.Our results show that serum cystatin C is a reliable marker for estimating glomerular filtration rate among renal transplant recipients. This test can determine the glomerular filtration rate of renal transplant recipients on follow-up. Further studies are required to establish serum cystatin C as a standard test for monitoring glomerular filtration rate in transplanted patients.
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To compare glomerular filtration rate measured by technetium-99m ([Tc99m]) DTPA clearance with estimated creatinine clearance (CrCl) (Cockcroft and Gault (C&G) method) in patients with serum creatinine (Scr) levels <0.06 mmol l−1, and determine the effect of rounding serum creatinine to 0.06 mmol l−1. Patients with serum creatinine values <0.06 mmol l−1 at the time of [Tc99m] clearance determination were identified. Creatinine clearance was calculated by the C&G method using both actual and rounded Scr values. A total of 419 adults had GFR measured by technetium-99m diethyl triamine penta-acetic acid ([Tc99m] DTPA) clearance. Out of this group, 26 patients had a serum creatinine value <0.06 mmol l−1. The C&G estimates of renal function using actual serum creatinine resulted in an overall overestimation of 12.9% when compared to [Tc99m] DTPA clearance. When the value of serum creatinine was rounded to 0.06 mmol l−1, the formula underestimated renal function by −7.0%. Analysis of estimated creatinine clearance for different levels of renal function showed significant differences to [Tc99m] DTPA clearance. Rounding up of serum creatinine to 0.06 mmol l−1 improved the predictive ability of the C&G method for the patients with [Tc99m] DTPA clearance ⩽100 ml min−1, but worsened the effect in those >100 ml min−1. This work indicates that when bedside estimates of renal function are calculated using the C&G formula actual Scr should be used first to estimate CrCl. If the resultant CrCl is ⩽100 ml min−1, then the Scr should be rounded up to 0.06 mmol l−1 and CrCl recalculated. Further assessment of this approach is warranted in a larger cohort of patients.
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Creatinine-based equations are used as standard ways to estimate glomerular filtration rate and kidney function. Unfortunately, serum creatinine varies based on factors such as age, gender, and muscle mass. Overestimation of renal function by creatinine-based equations can be dangerous for renally dosed medications, such as enoxaparin. We present a patient who developed spontaneous bleeding on enoxaparin where kidney function was significantly overestimated by creatinine-based equations. The use of cystatin C levels, which are creatinine independent, can provide a better prediction of renal function.
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We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.
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Serum creatinine remains the most widely used measure of renal function in clinical practice and in clinical trials. However, the serum concentration reflects not only renal excretion, which is composed of filtration and tubular secretion, but also the generation, intake, and metabolism of creatinine. Thus, serum creatinine does not provide an adequate estimate of glomerular filtration rate (GFR). Creatinine clearance is also an inaccurate and imprecise measure of GFR in clinical practice. The questions concerning the abnormality or the change of glomerular function can be answered with greater accuracy and precision by serum creatinine if the factors affecting its concentration are taken into account. The slope of the decline in reciprocal serum creatinine versus time does not accurately reflect changes in creatinine clearance and does not allow an accurate assessment of the rate of progression of renal disease. It can even be hazardous to use such value to observe the efficacy of treatments for progressive renal diseases.
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Objective To evaluation of endogenous clearance marker glomerular filtration rate(GFR) in patients with various types of renal diseases.Methods We determined the serum cystatin C,urea,creatinine,and creatinine clearance levels in 57 patients with renal diseases,and 39 healthy controls,and compared the concentrations of patients with of healthy controls.Results The concentratons of serum urea,creatinine,and creatinine clearance was found to be significantly higher in the patients with renal diseases in comparison to the healthy controls(P0.01).Correlation was observed between cystatin C and creatinine clearance levels(P0.05),and between cystatin C and creatinine levels(P0.01).However,there were not correlation between creatinine and urea concentrations(P0.05),and between creatinine and creatinine clearance lenels(P0.05).Conclusion Serum cystatin C is probably more attractive for estimation of renal function than urea,creatinine,and creatinine clearance for detection of GFR in patients with early kidney diseases.
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Creatinine is a metabolite excreted mainly by glomerular filtration, which makes it an important endogenous indicator of kidney function. Creatinine clearance is defined as the ratio of the concentration of creatinine in serum and urine. It assesses glomerular filtration. Creatinine and creatinine clearance have the leading role in the early diagnosis, monitoring and classification of chronic kidney disease. The routine method for determining the concentration of creatinine is the Jaffé photometric method. A newer version is the compensated method. Furthermore, the recommended equation for the estimation of glomerular filtration rate (GFR) is the one based on the MDRD study (eGFR) intended for people over 18 years. The aim of the study was to evaluate how the introduction of the compensated method would affect the clinical use and influence the assessment of GFR in the interpretation of findings and treatment monitoring for people over 20 years. The study group included 130 men and 142 women whose requested laboratory test was creatinine clearance. Data were collected over 20 days at Sestre milosrdnice University Hospital. Serum creatinine concentration and eGFR were determined by the compensated and uncompensated Jaffé method. In conclusion, the compensated creatinine method is not statistically comparable with the uncompensated method, but is clinically fully applicable to the general population above the age of 20, given that the reference intervals are changed. Comparison of eGFR as estimated by the compensated and uncompensated methods to determine creatinine concentration showed the same results as the comparison of clearance. Using the compensated method yielded statistically incomparable results in GFR estimation. However, in clinical practice, patient classification according to stages of chronic kidney disease (CKD) was comparable in the male group according to clearance and eGFR (pi=0.922 and pi=0.230, respectively), while the female group was classified significantly different according to clearance and eGFR (pi<0.016 and pi<0.001, respectively). Switching to the compensated creatinine method while simultaneously applying the eGFR formula was shown to be valid, as patient classification according to CKD stages was comparable (pi=0.921); thus, the methods are reliable for use instead of creatinine clearance in the general population with various diagnoses, which can be noted in all laboratories and which is, although inhomogeneous, routinely used to measure daily creatinine clearance.
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