Neutrophil Gelatinase-Associated Lipocalin in Kidney Transplantation Is an Early Marker of Graft Dysfunction and Is Associated with One-Year Renal Function
Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF ( ). Shortly after KTx (3–6？h), uNGAL values were higher in DGF recipients (on average +242？ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function. 1. Introduction Delayed graft function (DGF) is an important complication of kidney transplantation (KTx) that adversely affects allograft survival. Despite substantial improvements in the field of KTx, the incidence of DGF is rising with the growing practice of accepting expanded criteria donors to increase transplantation rates [1–6]. Delayed graft function predisposes kidney graft to acute and chronic rejection, contributes to progressive allograft dysfunction, and increases the risk of premature graft loss [7–11]. Reliable biomarkers enabling early discrimination of DGF in KTx are lacking, which impairs timely therapeutic interventions. Traditionally, acute graft dysfunction is diagnosed by measuring serum creatinine, but this parameter is an unreliable indicator of kidney function during an episode of acute injury [12]. One of the most promising biomarkers of acute kidney injury is neutrophil gelatinase-associated lipocalin (NGAL), which is released to blood from activated neutrophils during inflammatory processes. In steady situations, this lipocalin is found in urine only in trace. Massive NGAL quantities excreted in urine (uNGAL) usually indicate
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