Chronic renal failure among HIV-1-infected patients.
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.
Mocroft
Amanda
A
Royal Free Centre for HIV Medicine, and Department of Primary Care and Population Sciences, Royal Free and University College Medical Schools, Royal Free Campus, Rowland Hill Street, London, UK. a.mocroft@pcps.ucl.ac.uk
Kirk
Ole
O
Gatell
Jose
J
Reiss
Peter
P
Gargalianos
Panagiotis
P
Zilmer
Kai
K
Beniowski
Marek
M
Viard
Jean-Paul
JP
Staszewski
Schlomo
S
Lundgren
Jens D
JD
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D015497:HIV-1; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D019469:Indinavir / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D000068698:Tenofovir
D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine