Urine NGAL and IL-18 are Predictive Biomarkers for Delayed Graft Function Following Kidney Transplantation

TLDR

DGF, caused by tubular cell injury, frequently complicates deceased donor kidney transplants, with peak serum creatinine requiring dialysis typically 2–4 days after surgery. The study aimed to determine whether urinary neutrophil gelatinase‑associated lipocalin (NGAL) and interleukin‑18 (IL‑18) could serve as early biomarkers for DGF, defined as dialysis within the first week post‑transplant. Day‑0 urine from 23 living‑donor, 20 deceased‑donor prompt‑function, and 10 deceased‑donor DGF recipients was analyzed blind by ELISA for NGAL and IL‑18. NGAL and IL‑18 levels were markedly higher in the DGF group on day 0, with ROC AUCs of 0.9 for both, and multivariate analysis confirmed they predicted post‑transplant serum creatinine trends, establishing them as early predictive biomarkers of DGF.

Abstract

Delayed graft function (DGF) due to tubule cell injury frequently complicates deceased donor kidney transplants. We tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) represent early biomarkers for DGF (defined as dialysis requirement within the first week after transplantation). Urine samples collected on day 0 from recipients of living donor kidneys (n = 23), deceased donor kidneys with prompt graft function (n = 20) and deceased donor kidneys with DGF (n = 10) were analyzed in a double blind fashion by ELISA for NGAL and IL-18. In patients with DGF, peak postoperative serum creatinine requiring dialysis typically occurred 2-4 days after transplant. Urine NGAL and IL-18 values were significantly different in the three groups on day 0, with maximally elevated levels noted in the DGF group (p < 0.0001). The receiver-operating characteristic curve for prediction of DGF based on urine NGAL or IL-18 at day 0 showed an area under the curve of 0.9 for both biomarkers. By multivariate analysis, both urine NGAL and IL-18 on day 0 predicted the trend in serum creatinine in the posttransplant period after adjusting for effects of age, gender, race, urine output and cold ischemia time (p < 0.01). Our results indicate that urine NGAL and IL-18 represent early, predictive biomarkers of DGF.