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

Amanda Mocroft, Ole Kirk, Peter Reiss, Stephane De Wit, Dalibor Sedlacek, Marek Beniowski, Jose Gatell, Andrew N. Phillips, Bruno Ledergerber, Jens D. Lundgren, M. Losso, C. Elias, N. Vetter, R. Zangerle, I. Karpov, A. Vassilenko, V. M. Mitsura, O. Suetnov, N. Clumeck, B. PollR. Colebunders, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, L. Machala, H. Rozsypal, J. Nielsen, G. Kronborg, T. Benfield, M. Larsen, J. Gerstoft, T. Katzenstein, A. B. Hansen, P. Skinhøj, C. Pedersen, L. Oestergaard, K. Zilmer, J. Smidt, M. Ristola, C. Katlama, J. P. Viard, P. M. Girard, J. M. Livrozet, P. Vanhems, C. Pradier, F. Dabis, D. Neau, J. Rockstroh, R. Schmidt, J. van Lunzen, O. Degen, H. J. Stellbrink, S. Staszewski, J. Bogner, G. Fätkenheuer, J. Kosmidis, P. Gargalianos, G. Xylomenos, J. Perdios, G. Panos, A. Filandras, E. Karabatsaki, H. Sambatakou, D. Banhegyi, F. Mulcahy, I. Yust, D. Turner, M. Burke, S. Pollack, G. Hassoun, S. Maayan, A. Chiesi, R. Esposito, I. Mazeu, C. Mussini, C. Arici, R. Pristera, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, A. Chirianni, E. Montesarchio, M. Gargiulo, G. Antonucci, F. Iacomi, P. Narciso, C. Vlassi, M. Zaccarelli, A. Lazzarin, R. Finazzi, M. Galli, A. Ridolfo, A. d'Arminio Monforte, B. Rozentale, P. Aldins, S. Chaplinskas, R. Hemmer, T. Staub, J. Bruun, A. Maeland, V. Ormaasen, B. Knysz, J. Gasiorowski, A. Horban, E. Bakowska, D. Prokopowicz, R. Flisiak, A. Boron-Kaczmarska, M. Pynka, E. Mularska, H. Trocha, E. Jablonowska, E. Malolepsza, K. Wojcik, F. Antunes, E. Valadas, K. Mansinho, F. Maltez, D. Duiculescu, V. Babes, A. Rakhmanova, E. Vinogradova, D. Jevtovic, M. Mokrás, D. Staneková, J. Tomazic, J. González-Lahoz, V. Soriano, L. Martin-Carbonero, P. Labarga, S. Moreno, B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, J. M. Miró, P. Domingo, M. Gutierrez, G. Mateo, M. A. Sambeat, A. Karlsson, P. O. Persson, L. Flamholc, R. Weber, P. Francioli, M. Cavassini, B. Hirschel, E. Boffi, H. Furrer, M. Battegay, L. Elzi, E. Kravchenko, N. Chentsova, G. Kutsyna, S. Servitskiy, S. Antoniak, M. Krasnov, S. Barton, A. M. Johnson, D. Mercey, M. A. Johnson, M. Murphy, J. Weber, G. Scullard, M. Fisher, C. Leen, B. Gazzard, A. D'Arminio Montforte, N. Friis-Møller, A. Cozzi-Lepri, W. Bannister, M. Ellefson, A. Borch, D. Podlekareva, J. Kjaer, L. Peters, J. Reekie, J. Kowalska

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: 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. Design: A cohort study including 6843 HIV-positive persons with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. Methods: CKD was defined as either confirmed (two measurements ≥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. Results: 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 dugs were associated with increased incidence of CKD. Conclusion: 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.

Original languageEnglish
Pages (from-to)1667-1678
Number of pages12
JournalAIDS
Volume24
Issue number11
DOIs
StatePublished - 17 Jul 2010

Keywords

  • antiretroviral drugs
  • chronic kidney disease
  • estimated glomerular filtration rate

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