Renal dysfunction among HIV-infected patients starting antiretroviral therapy

Abstract

Objective HIV-related renal dysfunction is associated with high mortality. Data on the prevalence of renal dysfunction among HIV-infected outpatients starting antiretroviral therapy (ART) in sub-Saharan Africa is limited. Recent recommendations to include the nephrotoxic drug tenofovir in first-line ART regimens make clarification of this issue urgent. Methods We screened for renal dysfunction by measuring serum creatinine, proteinuria, and microalbuminuria in HIV-positive outpatients initiating ART in Mwanza, Tanzania. We excluded patients with preexisting renal disease, hypertension, diabetes, or Hepatitis C virus co-infection. Estimated glomerular filtration rates (eGFRs) were calculated by Cockroft-Gault and Modification of Diet in Renal Disease (MDRD) equations. Results Only 129 (36%) of 355 enrolled patients had normal eGFRs (Grade 0 or 1) above 90 ml/min/1.73m2. Grade 2 renal dysfunction (eGFR between 60 and 89 ml/min/1.73m2) was present in 137 patients (38.6%), and 87 patients (25%) had Grade 3 dysfunction (eGFR between 30 and 59 ml/min/1.73m2). Microalbuminuria and proteinuria were detected in 72% and 36% of patients, respectively. Factors predictive of renal dysfunction in multivariate analysis included female gender (OR 3.0, 95% confidence interval (CI) [1.8–5.1], p<0.0001), Body Mass Index (BMI) <18.5 (OR 2.3 [1.3–4.1], p=0.004), CD4+ T-cell count <200 cells/mm3 (OR 2.3 [1.1–4.8], p=0.04), and World Health Organization (WHO) clinical stage II or above (OR 1.6 [1.2–2.3], p=0.001). Conclusions Renal dysfunction was highly prevalent in this population of HIV-positive outpatients initiating first ART in Tanzania. This highlights the critical and underappreciated need to monitor renal function in HIV-positive patients in sub-Saharan Africa, particularly given the increasing use of tenofovir in first-line ART.

Renal Dysfunction among HIV-infected Patients on Tenofovir-Based Antiretroviral Therapy at Ronald Ross Hospital in Zambia

“…The prevalence found in this study agrees to similar studies done around the world ranging from 3.6% to 42% [9,12,21,22]. The risk factors for renal dysfunction that we found in this population are consistent with previous findings, for example, in the adult population at University Teaching Hospital, Zambia [9,10] which suggested that CD4+ cell counts is an important risk factor.…”

Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens

“…Studies set in Mwanza, Tanzania and Johannesburg, South Africa have shown that the prevalence of stage 2 CKD (eGFR 60 to 89 ml/min per 1.73 m) is 30–40% while the prevalence of stage 3 CKD (eGFR 30 to 59 ml/min per 1.73 m) is estimated to be 5.2% to up to 25% [21, 22]. Much of the incident kidney dysfunction in TDF patients was related to preexisting renal disorder [21].…”

Kidney Disease in HIV-Infected Persons

“…These studies describe wide variability in CKD prevalence among Africans living with HIV, ranging from 0.7% to 42% for GFR <60 ml/min/1.73 m 2 , including 0.7% to 18.9% in the largest studies [5,6,8,[32][33][34][35][36][37]. Proteinuria was detected in 6.1% to 23% of HIV-infected Africans, and lower CD4 cell counts were correlates of lower GFR and increased proteinuria in these studies.…”

“…All of these equations were validated in industrialized settings and may be less accurate in populations with lower dietary protein intake and lower average body weights [5]. Accordingly, and in contrast to industrialized settings, moderate renal impairment (<60 ml/min) was more frequently identified by the Caukcroft-Gault compared to the MDRD equation, in a large randomized clinical trial that compared routine versus clinically-driven laboratory monitoring of ART in the Development of Antiretroviral Therapy Trial (DART) in Uganda and Zimbabwe, and in several other studies from sub-Saharan Africa [6][7][8].…”