Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation

Abstract

Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immuno-suppressant for heart transplant (HTx) recipients, and is expected to preserve renal function compared to conventional calcineurin inhibitors (CNIs). However, a considerable number of recipients treated with EVL were not free from worsening renal function regardless of CNI reduction. Data were collected retrospectively from 27 HTx recipients who had received EVL (trough concentration, 3.1-9.2 ng/mL) along with reduced CNIs (%decreases in trough concentration, 27.3 ±13.0%) because of switching from mycophenolate mophetil due to digestive symptoms or neutropenia, progressive coronary artery vasculopathy, or persistent renal dysfunction, and had been followed over 1 year between August 2008 and January 2013. Estimated glomerular fltration rate (eGFR) decreased in 5 recipients (18.5%) during the study period. Univariate logistic regression analysis demonstrated that a higher plasma neutrophil gelatinase-associated lipocalin (P-NGAL) level was the only signifcant predictor for a decrease in eGFR over a 1-year EVL treatment period among all baseline parameters (P = 0.008). eGFR and proteinuria worsened almost exclusively in patients with baseline P-NGAL = 85 ng/mL, which was the cutoff value calculated by an ROC analysis (area under the curve, 0.955; sensitivity, 1.000; specifcity, 0.955). In conclusion, higher P-NGAL may be a novel predictor for the worsening of renal function after EVL treatment that is resistant to CNI reduction in HTx recipients.