Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia

Abstract

Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment.

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.…”

“…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. Other studies have suggested an association between CD4+ cell count of less than 200 cells/uL and renal dysfunction among patients exposed to TDF [6,9,23]. In this study, the median CD4+ cell count was 243.9 cells/ uL for those with CrCl>50ml/uL eliminating the assumption that renal dysfunction in this group could have been due to advanced HIV infection.…”

“…In Zambia, national guidelines recommends close renal monitoring at 2 weeks, 3 months and thereafter 6 monthly review of renal function for patients on ART. Mulenga and co-workers, recommends that if TDF is used as part of first line regimen, as is the case in Zambia, benefits should be weighed against the more intensive renal monitoring that has to follow [9]. We argue that although TDF-based regimes are used, there is limited information on the proportion of patients that develop renal dysfunction.…”

“…TDF has been considered safe and associated with fewer side-effects in many clinical trials [4,5,8]. However, there have been many case reports, cross sectional and cohort studies describing TDF associated and non-TDF associated nephrotoxicity [9][10][11][12]. However, there is increasing evidence suggesting that TDF has been associated with renal abnormalities [13] and more specifically that it can cause mild to moderate renal dysfunction [10,[12][13][14][15].…”

Timing of antiretroviral therapy initiation in adults with HIV-associated tuberculosis: Outcomes of therapy in an urban hospital in KwaZulu-Natal

“…A study in Lusaka demonstrated that even mild (GFR 60 -89 ml/min) baseline renal insufficiency was associated with increased mortality after ART initiation. 13 This is important, as tenofovir is now part of the first-line HIV treatment regimen in South Africa. Screening for renal insufficiency is recommended before initiating ART, and patients with renal impairment must be followed up regularly.…”