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The role of serum cystatin C (Scyc), neutrophil gelatinase-associated lipocalin, and interleukin-18 in predicting early graft function after kidney transplant is poorly defined.We conducted a multicenter prospective cohort study of deceased-donor kidney transplants. We collected serial blood samples for the first 3 days of transplant and monitored need for dialysis within 1 week and graft function at 3 months after transplant.Among 78 recipients with serum biomarker measurements, 26 had delayed graft function (DGF; hemodialysis within 1 week of transplant). Of those not dialyzed, 29 had slow graft function (serum creatinine [Scr] reduction from transplantation to day 7 <70%), and 23 had immediate graft function (IGF; reduction in Scr ≥70%). Scyc levels were statistically different between groups by the first postoperative day (POD), whereas Scr levels were not. Serum neutrophil gelatinase-associated lipocalin and serum interleukin-18 levels were not different between groups. Scyc on the first POD demonstrated good utility for predicting DGF and non-IGF (DGF or slow graft function) with areas under the receiver-operating characteristic curve of 0.83 and 0.85, respectively. Areas under the receiver-operating characteristic curve for predicting DGF and non-IGF using Scr on the first POD were 0.65 and 0.53, respectively. Substituting Scyc for Scr in a clinical algorithm improved its utility for predicting DGF or non-IGF, with adjusted odds ratios of 2.4 and 3.3 for Scyc levels on the first POD. The change in Scyc during the first POD demonstrated a dose-response relationship with 3-month graft function.Scyc outperforms Scr as a predictor of early graft function after deceased-donor kidney transplant.