Tenofovir clearance is reduced in HIV-positive patients with subclinical tubular impairment

Objective:To assess if tenofovir (TFV) clearance is associated with urinary retinal-binding protein (RBP) in HIV-positive patients with normal estimated filtration rate.Design:A cross-sectional diagnostic study.Methods:HIV-positive patients with estimated creatinine clearance above 60ml/min, on tenofovir disoproxil fumarate (TDF)-containing combination since at least 6 months, taking TDF at night, and without significant comorbidities (diabetes, untreated hypertension, known renal malformations, recurrent nephrolithiasis) and nephrotoxic drugs were included. TFV plasma and urinary concentrations were measured 12h after drug intake (C-12). RBP was measured through enzyme immunoassay kit on spot urines and corrected per urinary creatinine (uRBP/uCr); normality ranges were below 130g/g (in patients aged <50 years) and below 172g/g (in patients aged 50 years).Results:Two hundred and eighty-nine patients were included (median age of 45.8 years, 71.6% male and 85.4% whites); patients were concomitantly treated with nonnucleoside reverse transcriptase inhibitors (155, 53.6%), protease inhibitors (118, 40.8%), or integrase inhibitors (16, 5.5%)-containing regimens. Estimated creatinine clearance was 89.4ml/min (78.6-105.9). Urinary RBP (uRBP) and uRBP/uCr were 204.6ng/ml (92-380) and 169.7g/g (85.8-318.3), respectively; abnormally high uRBP/uCr was observed in 157 patients (54.3%). A multivariate binary logistic regression confirmed that both ethnicity (P=0.004, 2.93, 95% confidence interval 1.41-6.10) and TFV urinary C-12 less than 21mg/ml (P=0.006, 2.04, 95% confidence interval 1.12-3.41) were significantly associated with abnormal uRBP/uCr.Conclusion:HIV-positive TDF-treated patients showed a high prevalence of proximal tubular impairment: ethnicity (whites) and low urinary TFV concentrations were significantly associated with elevated uRBP.SDC video:http://links.lww.com/QAD/A852. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.