Prevalence and significance of proximal renal tubular abnormalities in HIV-infected patients receiving tenofovir.

Abstract

Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial. Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV-infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study. PRTD was defined as two or more tubular abnormalities. After a median of 65 months (interquartile range, 42.7-84.7), at least one tubular alteration was found in 72% of patients, mostly proteinuria (42, 50, and 14% in current, previous and never TDF use; P=0.02) and phosphaturia (46, 42, and 14%; respectively, P < 0.01). PRTD was found in 63 patients (32%) receiving TDF, ranging from 14 to 46% according to concomitant hepatitis C virus coinfection, diabetes mellitus or hypertension arterial, in contrast with six (23%) following TDF discontinuation, and zero cases in no TDF-treated patients. The use of TDF [odds ratio (OR) 13.2; 95% confidence interval (CI) 1.4-22.7; P = 0.01], cumulative time on combination antiretroviral therapy (OR 1.011; 95% CI 1.07-1.019 per month; P = 0.01), and baseline estimated glomerular filtration rate (eGFR, OR 0.97; 95% CI 0.94-0.99 per ml/min per 1.73 m higher; P = 0.04) were associated with PRTD. The number of tubular abnormalities was linearly associated with eGFR decline since TDF initiation (β-coefficient -0.15, P = 0.02), together with age (-0.18; P = 0.01), baseline eGFR (0.49, P = 0.01), diabetes mellitus (-0.19, P = 0.02), and time on TDF (-0.23; P = 0.01). The use of TDF leads to an increased rate of tubular dysfunction, and modulated by age, baseline eGFR, and classical factors, is associated with kidney function decline.