Urinary Neutrophil Gelatinase-Associated Lipocalin as a Predictive Biomarker for the Progression of Renal Injury in Liver Transplant Recipients using Calcineurin Inhibitors

Abstract

Introduction: Calcineurin inhibitors (CNI) are commonly used in liver transplant (LT) recipients, though a known side effect is nephrotoxicity. Neutrophil gelatinase-associated lipocalin (NGAL) is a marker that is expressed in the kidneys after renal ischemia. We sought to evaluate the feasibility of NGAL as an early predictor of renal impairment in patients under CNI therapy. Methods: Urine samples were obtained cross-sectionally from LT patients who visited the outpatient clinic from February 2016 to June 2016. Glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5-7 months later. Patients were divided into 3 groups according to the GFR at the time of urine sampling and the severity of renal dysfunction (Normal [GFR: > 90 mL/min/1.73 m2], Mild [GFR: 60-89 mL/min/1.73 m2], Moderate [GFR: 30-59 mL/min/1.73 m2]). They were then further divided into 2 groups according to urinary NGAL level (NGAL-High [urinary NGAL > 25 ng/mL], NGAL-Low [urinary NGAL < 25 ng/mL]). Progression of renal injury was defined as a decrease in GFR greater than 5 mL/min/1.73 m2 in the Mild or Moderate groups, or if the patient was shifted to either the Mild or Moderate group from the Normal group during the follow-up period. Results: Fifty-one patients were enrolled in this study. Mean NGAL level was higher in the Moderate group than in the Normal and Mild groups (18.38 ± 14.31 vs. 7.74 ± 8.13, p < 0.01). A proportion of NGAL-High was also significantly higher in the Moderate group than in the Mild group (40% vs. 5%, p = 0.03). In the Mild and Moderate groups, NGAL-High was shown to be a significant risk factor for Progression of renal injury after follow-up by multivariate analysis (hazard ratio: 72.44

confidence interval : 1.283-4088.25), p=0.04). Conclusion: Increased NGAL can be a marker of low GFR, as well as a predictor of renal injury after short-term follow-up in patients with mild to moderate renal impairment.