Urinary Neutrophil Gelatinase-Associated Lipocalin Accurately Detects Acute Allograft Rejection Among Other Causes of Acute Kidney Injury in Renal Allograft Recipients

Background: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has emerged an early marker protein, predicative of acute kidney injury (AKI) in various clinical settings. Here, we demonstrate urinary NGAL to allow for differential diagnosis of AKI, accurately discriminating acute allograft rejection from other causes of AKI in renal allograft recipients. Methods: Urinary NGAL was assessed in spot urine of 182 outpatient renal allograft recipients on maintenance immunosuppression. Samples were blinded and NGAL concentrations determined by enzyme-linked immunosorbent assay. Patient data were classed according to standard criteria into stable allograft function or AKI, and according to underlying pathology into acute allograft rejection or AKI of other cause. Results: Of the 182 patients investigated, 44 (24.2%) presented with AKI and 9 (4.9%) were diagnosed with acute allograft rejection. In 138 patients with stable allograft function, median urinary NGAL concentration was 7.8 ng/mL (interquartile range, 3.7-17.4 ng/mL). In acute allograft rejection, urinary NGAL concentration was 339 ng/mL (165-499 ng/mL), and in AKI of other cause was 59.1 ng/mL (33.1-136 ng/mL). With a cut-off at 100 ng/mL, urinary NGAL accurately predicted acute rejection as underlying pathology of AKI in our cohort (area under the curve-receiver operating characteristic 0.98, sensitivity 1.0, specificity 0.93). This concept was confirmed in an independent clinical setting in allograft recipients referred to our hospital with AKI. Conclusions: Urinary NGAL, at respective cut-off, accurately discriminates acute allograft rejection from other causes of AKI in follow-up after kidney transplantation. As a readily available parameter, urinary NGAL may guide differential diagnosis and initial therapy in allograft recipients with AKI.