Urine Cystatin C as a Biomarker of Proximal Tubular Function Immediately after Kidney Transplantation

Background/Aims: Clinical methods to predict allograft function soon after kidney transplantation are ineffective. Methods: We analyzed urine cystatin C (CyC) in a prospective multicenter observational cohort study of deceaseddonor kidney transplants to determine its peritransplant excretion pattern, utility for predicting delayed graft function (DGF) and association with 3-month graft function. Serial urine samples were collected for 2 days following transplant and analyzed blindly for CyC. We defined DGF as any hemodialysis in the first week after transplant, slow graft function (SGF) as a serum creatinine reduction ! 70% by the first week and immediate graft function (IGF) as a reduction 6 70%. Results: Of 91 recipients, 33 had DGF, 34 had SGF and 24 had IGF. Urine CyC/urine creatinine was highest in DGF for all time-points. The area under the curve (95% CI) for predicting DGF at 6 h was 0.69 (0.57–0.81) for urine CyC, 0.74 (0.62–0.86) for urine CyC/urine creatinine and 0.60 (0.45–0.75) for percent change in urine CyC. On the first postoperative day, Received: December 14, 2010 Accepted: February 24, 2011 Published online: April 15, 2011 Nephrology American Journal of Chirag Parikh, MD, PhD Section of Nephrology, Yale University and VAMC 950 Campbell Ave, Mail Code 151B, Bldg 35 A, Room 219 West Haven, CT 06516 (USA) Tel. +1 203 932 5711, ext. 4300, E-Mail Chirag.Parikh @ Yale.edu © 2011 S. Karger AG, Basel Accessible online at: www.karger.com/ajn D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 3/ 20 17 4 :1 8: 09 P M Hall /Koyner /Doshi /Marcus /Parikh Am J Nephrol 2011;33:407–413 408 approximately one third of recipients [2, 3] . While DGF is typically defined as hemodialysis in the first week following kidney transplantation, slow graft function (SGF) has been defined by various serum creatinine (Cr) cutoff values during the first several days of transplant [4, 5] . Compared with immediate graft function (IGF), however, both diagnoses are associated with worse long-term outcomes [2, 5, 6] . Researchers have discussed replacing serum Cr in clinical practice with serum cystatin C (CyC) for years. CyC is a 13.4-kDa cysteine protease inhibitor produced in all nucleated cells. It is released into the circulation at a constant rate, freely filtered by glomeruli, taken up by proximal tubular cells for degradation (without return to the circulation) and undergoes no tubular secretion. Studies have described the superiority of serum CyC over serum Cr for diagnosing filtration failure in the setting of AKI [7, 8] . In health, the amount of detectable urinary CyC is low ( ! 0.28 mg/l) because of effective proximal tubular reabsorption/degradation of this low-molecularweight protein and is unrelated to characteristics like gender and age [9] . Urine CyC concentrations increase with AKI due to decreased reabsorption from injured/ dysfunctional tubules. As such, urine CyC can be considered a marker of proximal tubular function and has been described as an effective urinary AKI biomarker in adults following cardiac surgery and admission to medical/surgical intensive care [10–12] . No study, however, has reported urine CyC excretion patterns immediately following kidney transplantation or described its utility for detecting/predicting allograft function in the peritransplant setting. We recently demonstrated that urinary neutrophil gelatinase-associated lipocalin and IL-18 within the first 24 h following transplant predict DGF better than changes in serum Cr and correlate with 3-month allograft function in a multicenter prospective-cohort study of nonpreemptive deceased-donor kidney transplants [1] . Utilizing this cohort, our primary goal for the current study was to describe urine CyC excretion patterns immediately following transplant in recipients with DGF, SGF and IGF. In addition, we sought to determine the degree of association between peritransplant urine CyC levels and 3-month allograft function.