Neutrophil Gelatinase-Associated Lipocalin in Kidney Transplantation Is an Early Marker of Graft Dysfunction and Is Associated with One-Year Renal Function

Abstract

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 (n = 18). 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.

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

“…It has been reported that kidney epithelia express and excrete large quantities of NGAL into urine following acute injury, reaching up to 1000‐fold induction of NGAL mRNA and protein in the most severe cases 33. There is a large body of literature to indicate that uNGAL increases during the first posttransplant week in renal transplant recipients with DGF, especially in the very early urine samples collected within six h postsurgery 34, 35, 36. Thus, the main potential advantage arising from this finding is the possibility to identify and stratify patients according to their risk of dialysis need after transplant, prior to the diagnosis of DGF.…”

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

“…Different urinary biomarkers from recipients are also reported to predict primary non function (29)(30)(31)(32)(33). However, estimate recipient urinary biomarkers are not useful to make decisions regarding the acceptance and the subsequent allocation of cadaveric kidneys.…”

Prognostic Value of Osteoprotegerin in Acute Heart Failure

“…Detailed results regarding each biomarker were previously reported [13][14][15]. Briefly, levels of uNGAL, serum MDA, leptin and CysC were significantly higher in DGF patients.…”

“…We recently demonstrated, in a prospective cohort study, that urinary neutrophil gelatinase-associated lipocalin (uNGAL) [13], serum cystatin C (CysC) and malondialdehyde (M.DA) [14], and serum leptin [15] within the first 24 h following KTx predicted DGF better than SCr levels or changes in SCr levels. Utilizing the same cohort, our primary goal for the current study was to investigate the value of combining these new markers with the widely used SCr level in predicting DGF (defined as dialysis requirement within the first week after KTx).…”