Background: The role of exposure to antiretrovirals in chronic renal failure (CRF) is not well understood. Glomerular filtration rates (GFR) are estimated using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations.
Methods: Baseline was arbitrarily defined as the first recorded GFR; patients with two consecutive GFR < or = 60 ml/min per 1.73 m(2) were defined as having CRF. Logistic regression was used to determine odds ratio (OR) of CRF at baseline. ART exposure (yes/no or cumulative exposure) prior to baseline was included in multivariate models (adjusted for region of Europe, age, prior AIDS, CD4 cell count nadir, viral load, hypertension and use of nephrotoxic anti-infective therapy).
Results: Using CG, the median GFR at baseline (n = 4474) was 94.4 (interquartile range, 80.5-109.3); 158 patients (3.5%) had CRF. Patients with CRF were older (median, 61.9 versus 43.1 years), had lower CD4 cell count nadirs (median, 80 versus 137 cells/microl), and were more likely to be diagnosed with AIDS (44.3 versus 30.4%), diabetes (16.5 versus 4.3%) or hypertension (53.8 versus 26.4%), all P < 0.001. In a multivariate model any use of indinavir [odds ratio (OR) 2.49; 95% confidence interval (CI), 1.62-3.83] or tenofovir (OR, 2.18; 95% CI, 1.25-3.81) was associated with increased odds of CRF, as was cumulative exposure to indinavir (OR, 1.15 per year of exposure; 95% CI, 1.06-1.25) or tenofovir (OR, 1.60; 95% CI, 1.20-2.15). Highly consistent results were seen using the MDRD formula.
Conclusions: Among antiretrovirals, only exposure to indinavir or tenofovir was associated with increased odds of CRF. We used a confirmed low GFR to define CRF to increase the robustness of our analysis, although there are several potential biases associated with this cross-sectional analysis.