Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

• Published in: AIDS (London) Vol. 24; no. 11; pp. 1667 - 1678
• Main Authors: MOCROFT, Amanda, KIRK, Ole, REISS, Peter, DE WIT, Stephane, SEDLACEK, Dalibor, BENIOWSKI, Marek, GATELL, Jose, PHILLIPS, Andrew N, LEDERGERBER, Bruno, LUNDGREN, Jens D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 17.07.2010
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adult; AIDS/HIV; Anti-HIV Agents - adverse effects; Atazanavir Sulfate; Biological and medical sciences; Disease Progression; Epidemiologic Methods; Female; Glomerular Filtration Rate - drug effects; Glomerulonephritis; HIV Seropositivity - drug therapy; HIV Seropositivity - epidemiology; HIV Seropositivity - physiopathology; HIV-1; Human immunodeficiency virus; Human viral diseases; Humans; Indinavir - adverse effects; Infectious diseases; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - epidemiology; Kidney Failure, Chronic - physiopathology; Kidneys; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Oligopeptides - adverse effects; Organophosphonates - adverse effects; Pyridines - adverse effects; Reverse Transcriptase Inhibitors - adverse effects; Tenofovir; Urinary system involvement in other diseases. Miscellaneous; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Kidney disease; Glomerulonephritis; Immunopathology; Antiretroviral agent; Urinary system disease; Filtration; estimated glomerular filtration rate; AIDS; Chronic kidney disease; Immune deficiency; Infection; Viral disease; Renal failure; Antiviral; antiretroviral drugs
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/qad.0b013e328339fe53

Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. A cohort study including 6843 HIV-positive persons with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. CKD was defined as either confirmed (two measurements >or=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above 60 ml/min per 1.73 m or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m or less, using the Cockcroft-Gault formula. Poisson regression was used to determine factors associated with CKD. Two hundred and twenty-five (3.3%) persons progressed to CKD during 21 482 person-years follow-up, an incidence of 1.05 per 100 person-years follow-up [95% confidence interval (CI) 0.91-1.18]; median follow-up was 3.7 years (interquartile range 2.8-5.7). After adjustment for traditional factors associated with CKD and other confounding variables, increasing cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P < 0.0001), indinavir (IRR 1.12, 95% CI 1.06-1.18, P < 0.0001), atazanavir (IRR 1.21, 95% CI 1.09-1.34, P = 0.0003) and lopinavir/r (IRR 1.08, 95% CI 1.01-1.16, P = 0.030) were associated with a significantly increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral drugs were associated with increased incidence of CKD. In this nonrandomized large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD, as was true for indinavir and atazanavir, whereas the results for lopinavir/r were less clear.