Cumulative exposure of TDF is associated with kidney tubulopathy whether it is currently used or discontinued.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) increases the risk of kidney tubular dysfunction (KTD). This study was conducted to elucidate whether KTD persists after discontinuation of TDF. DESIGN: A prospective cross-sectional study which enrolled 941 HIV-1-infected patients. METHODS: KTD was predefined as the presence of at least two abnormalities among the five tubular markers (fractional excretion of phosphate, fractional excretion of uric acid, ß2 microglobulinuria, N-acetyl-ß-D-glucosaminidase, nondiabetic glycosuria). Logistic regression model was used to examine the association between KTD and cumulative TDF use, as well as current status of TDF use. RESULTS: In total, 94% of study patients were men (median age 45, estimated glomerular filtration rate 75 ml/min per 1.73 m, CD4 575 cells/µl. About 98% were on antiretroviral therapy. In total, 64% of the patients ever used TDF and 39% currently used TDF. Twenty-nine percent used TDF for more than 5 years. KTD was diagnosed in 116 (12%) patients. In multivariate model, more than 5 years of TDF exposure and current TDF use [odds ratio (OR) 4.2, 95% confidence interval (CI) 2.37-7.56], more than 5 years and past TDF use (OR 2.4, 95% CI 1.09-5.33), less than 5 years and current TDF (OR 2.4, 95% CI 1.24-4.85), and less than 5 years and past TDF (OR 2.4, 95% CI 1.22-4.64) were all significantly associated with KTD, with never TDF use as reference. The results were the same using 4 and 3 years of exposure as the cutoff. However, with 2 years exposure, both less than 2 years and current TDF (OR 2.3, 95% CI 0.84-6.20) and less than 2 years and past TDF (OR 1.9, 95% CI 0.73-4.93) were not associated with KTD, whereas both more than 2 years and current TDF and more than 2 years and past TDF were associated. CONCLUSION: The association between cumulative TDF use and KTD was strong and robust. The results of the study suggested that TDF-related KTD might persist after discontinuation of TDF if patients used TDF for more than 2 years.

Prevalence and factors associated with chronic kidney disease and end-stage renal disease in HIV-1-infected Asian patients in Tokyo.

This single-center cross-sectional study determined the prevalence and factors associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD) in HIV-1-infected Asian patients at the largest HIV clinic in Japan. HIV-1-infected patients who visited the clinic between September and December 2016 were analyzed. CKD was defined as estimated glomerular filtration rate of <60 ml/min/1.73 m2 or proteinuria ≥1+, observed at least over three months. A logistic regression model was used to estimate the effects of various variables on CKD. The study included 1,990 patients; with 97% Asians, 34% aged of ≥50 years, and 94% had HIV-1 load <50 copies/ml. The median time from HIV-1 diagnosis to study enrollment and duration of ART were 9.1 years (IQR4.8-14.2) and 7.35 years (IQR3.28-12), respectively. CKD and ESRD were diagnosed in 256 (13%) and 9 (0.5%) patients, respectively. The prevalence of CKD was 18.6% for age 50-59, 28.5% for 60-69, and 47% for over 70. Older age, heavier body weight, diabetes mellitus, hypertension, and longer duration of ART, but not duration of TDF exposure, were associated with CKD. The traditional risk factors, rather than HIV-1-related variables, were associated with CKD, suggesting the importance of management of such comorbidities in maintenance of renal function.