Mulenga, L. B. et al. Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. AIDS 22, 1821-1827

Centre for Infectious Disease Research, Zambia.
AIDS (London, England) (Impact Factor: 5.55). 10/2008; 22(14):1821-7. DOI: 10.1097/QAD.0b013e328307a051
Source: PubMed


To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in an urban African setting.
Open cohort evaluation.
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 equation, and serum creatinine.
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, 8456 (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)(1/4)1.7; 95% confidence interval (95% CI)(1/4)1.5-1.9], moderately (AHR(1/4)2.3; 95% CI(1/4)2.0-2.7), and severely (AHR(1/4)4.3; 95% CI(1/4)3.1-5.5) reduced creatinine clearance. Mild (AHR(1/4)1.4; 95% CI(1/4)1.2-1.6), moderate (AHR(1/4)1.9; 95% CI(1/4)1.5-2.3), and severe (AHR(1/4)3.6; 95% CI(1/4) 2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared with those with normal renal function. Trends were similar when renal function was estimated with Modification of Diet in Renal Disease or serum creatinine.
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 pretreatment assessment.

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Available from: Lloyd B Mulenga, Oct 05, 2015
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    • "According to this survey, the incidence rate of CKD/ESRD/renal death was 1.32/1000 person-years of follow-up and the independent predictors of the endpoint included any cardiovascular event, lower eGFR and CD4 count [2]. Other studies investigating the prevalence of CKD among HIV infected subjects (defined as the presence proteinuria and/or glomerular filtration rate (GFR) lover than 60 ml/min) report on 3.5-4.7% in Europe, Argentina and Israel [3], 11 % in USA [4], 33 to 38 % in Zambia [5] and Nigeria [6], and 48.5% in Uganda [7], respectively. In our experience, in a sample of 1151 subjects with HIV infection followed at the University of Modena and Reggio Emilia, a normal renal function (defined as an estimated GFR greater than 90 ml/min/1.73 "
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    • "Studies from several countries in sub-Saharan Africa have demonstrated a high prevalence of renal dysfunction in HIV-infected individuals, reporting that 34% to 77% of patients have estimated glomerular filtration rates (eGFRs) <90 ml/min/1.73 m2 [3]–[6]. At our hospital, we recently found that 64% of HIV-infected patients had decreased eGFRs at the time of beginning ART, while 72% had microalbuminuria [7]. "
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    PLoS ONE 02/2014; 9(2):e89573. DOI:10.1371/journal.pone.0089573 · 3.23 Impact Factor
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    • "The choice of one specific drugs versus another primarily depends on tolerance: hematologic and renal toxicity guiding the choice between zidovudine and tenofovir; and skin toxicity, hepatotoxicity, fetotoxicity and interaction with rifampicin guiding the choice between efavirenz and nevirapine [44–46]. In recent years, evidence was specifically lacking in relation to the renal toxicity of tenofovir in a context of high prevalence of chronic kidney disease [47,48], as well as on efavirenz’ fetotoxicity. There is now stronger evidence on tenofovir's use in LMIC which clearly shows that (1) renal toxicity exists, justifying existing recommendations on monitoring creatinine clearance and/or dipstick screening for proteinuria [28]; (2) only a small percentage of patients exposed to tenofovir for at least 12 months developed severe renal intolerance, which does not make this drug more toxic than zidovudine, abacavir or nevirapine [28,49–51]. "
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