Prospective evaluation of cystatin C in the assessment of kidney dysfunction and survival in liver transplant candidates.

Kidney dysfunction is associated with decreased survival in liver transplant (LT) candidates, yet serum creatinine (sCr) is a poor surrogate for glomerular filtration rate (GFR) in this population. Serum cystatin C (CysC) may provide a more accurate assessment of kidney function and predict outcomes. We performed a multicenter prospective cohort study of consecutive LT candidates. CysC was obtained at LT evaluation (n=244) and a subset underwent simultaneous I125-iothalamate clearance for measured GFR (mGFR) assessment (n=137). Patients were followed to assess need for pre-LT renal replacement therapy (RRT), simultaneous liver-kidney transplant (SLKT), and survival. Estimated GFR (eGFR) based on MDRD-4, GRAIL, Royal Free Hospital Cirrhosis GFR, and the CKD-EPI equations was assessed for bias, precision, and accuracy in reference to mGFR. Receiver operator characteristic (AUROC) and competing risks survival analyses were performed. CysC more accurately discriminated mGFR than sCr at thresholds of ≤60 mL/min/1.73 m2 and ≤30 mL/min/1.73 m2 with AUROC 0.92 (p=0.005) and 0.96 (p=0.01), respectively. All eGFR equations overestimated GFR, especially among females (p<0.05). The GRAIL equation demonstrated the least bias, while CKD-EPI-cystatin C was associated with the greatest precision and lowest frequency of GFR overestimation. Among 165 LT recipients, CysC discriminated pre-LT renal replacement therapy and the need for simultaneous liver-kidney transplant with AUROC of 0.70 and 0.85, respectively. Cumulative incidence of death, accounting for LT as a competing event, increased with CysC (p=0.002) but was not observed with sCr overall or among subgroups (p=NS). CysC more accurately predicts thresholds of mGFR than sCr in LT candidates. Elevated CysC discriminates pre-LT RRT and SLKT, and is strongly associated with survival in contrast with sCr. CysC is a promising tool to improve prognostication among LT candidates.