Abstract
ObjectiveTo examine the role of antiretroviral drugs (ART), HIV-related and traditional risk factors on the incidence of chronic kidney disease (CKD) in HIV-infected patients.DesignProspective hospital-based cohort of HIV-infected patients from 2004 to 2012.MethodsCKD was defined using MDRD equation as an estimated glomerular filtration rate (eGFR) less than 60 ml/mn/1.73 m2 at 2 consecutive measurements ≥3 months apart. Poisson regression models were used to study determinants of CKD either measured at baseline or updated. ART exposure was classified as ever or never. We additionally tested the role of tenofovir (TDF), whether or not prescribed concomitantly with a Protease Inhibitor (PI), taking into account the cumulative exposure to the drug.Results4,350 patients (74% men) with baseline eGFR>60 ml/mn/1.73 m2 were followed for a median of 5.8 years. At the end of follow-up, 96% had received ART, one third of them (35%) jointly received TDF and a PI. Average incidence rate of CKD was 0.95% person-years of follow-up. Incidence of CKD was higher among women (IRR = 2.2), older patients (>60 y vs <45 y: IRR = 2.5 and 45–60 y: IRR = 1.7), those with diabetes (IRR = 1.9), high blood pressure (IRR = 1.5), hyperlipidemia (IRR = 1.5), AIDS stage (IRR = 1.4), low baseline eGFR (IRR = 15.8 for 60<eGFR<70 ml/mn/1.73 m2 vs >90 and IRR = 7.1 for 70<eGFR<80 ml/mn/1.73 m2), current CD4+<200 cells/mm3 vs >500/mm3 (IRR = 2.5), and exposure to TDF (IRR = 2.0). Exposure to TDF was even strongly associated with CKD when co-administered with PIs (IRR = 3.1 vs 1.3 when not, p<0,001). A higher risk of CKD was found when tenofovir exposure was >12 months [IRR = 3.0 with joint PIs vs 1.3 without (p<0.001)]. A vast majority of those developing CKD (76.6%) had a baseline eGFR between 60 and 80 ml/mn/1.73 m2.ConclusionIn patients with eGFR between 60 and 80 mL/min/1.73 m2, a thorough control of CKD risk factors is warranted. The use of TDF, especially when co-administered with PIs, should be mentioned as a relative contraindication in presence of at least one of these risk factors.
Highlights
Chronic kidney disease (CKD) is defined by the National Kidney Foundation as evidence of either kidney damage or glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 that persists for at least 3 months [1]
933 were excluded from the analysis for the following reasons: estimation of estimated glomerular filtration rate (eGFR) by MDRD formula was not applicable for 412 patients (pregnant women, Body Mass Index (BMI),18 kg/m2 or BMI .30 kg/m2, creatinine concentration,30 mmol/L, ascites, insufficient data to use and calculate MDRD formula), patients had MDRD,60 mL/min and were considered prevalent cases of chronic kidney disease (CKD) and patients had less than two eGFR measures after the first normal one
Median annual eGFR decline in patients who progressed to CKD was 9.0 ml/mn/1.73 m2 [IQR: 3.8; 17.8]
Summary
Chronic kidney disease (CKD) is defined by the National Kidney Foundation as evidence of either kidney damage or glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 that persists for at least 3 months [1]. CKD is an important risk factor of cardio-vascular morbidity, hospitalizations and mortality, in the general population as in HIV-infected patients [2,3]. Since the widespread availability of combination antiretroviral therapy (ART), HIVAN is rare but a longer survival of treated HIV-infected patients may expose them to other harmful factors for renal function. Traditional risk factors of CKD previously identified in the general population [9,10] are frequently reported among HIV infected patients [6,11,12]. Low CD4 count, high plasma HIV RNA or a history of AIDS-defining diagnosis, have been associated with a higher incidence of CKD [7,11,12,13]
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