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  • Review Article
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The nephrotoxic effects of HAART

Nature Reviews Nephrology volume 5, pages 563–573 (2009)Cite this article

Abstract

With significant reductions in mortality and risk of progression to AIDS in the era of highly active antiretroviral therapy (HAART), complications of long-standing HIV infection and treatment have become increasingly important. Such complications include the nephrotoxic effects of HAART, which are the subject of this Review. The most common nephrotoxic effects associated with HAART include crystal-induced obstruction secondary to use of protease inhibitors (mainly indinavir and atazanavir), and proximal tubule damage related to the nucleotide analog reverse transcriptase inhibitor tenofovir. Acute kidney injury (AKI) can occur following tenofovir-induced tubule dysfunction or as a result of severe mitochondrial dysfunction and lactic acidosis induced by nucleoside reverse transcriptase inhibitors. The potential insidious long-term renal toxicity of antiretroviral treatment is probably underappreciated in patients with HIV: a proportion of patients with treatment-related AKI did not recover their baseline renal function at 2-year follow-up, suggesting the possibility of permanent renal damage. Finally, nonspecific metabolic complications might increase the risk of vascular chronic kidney disease in patients on HAART. However, given the benefits of HAART, fear of nephrotoxic effects is never a valid reason to withhold antiretroviral therapy. Identification of patients with pre-existing chronic kidney disease, who are at increased risk of renal damage, enables appropriate dose modification, close monitoring, and avoidance or cautious use of potentially nephrotoxic medications.

Key Points

  • HIV suppression by highly active antiretroviral therapy (HAART) is associated with improvements in glomerular filtration rate

  • HAART itself can cause renal toxic effects

  • Identifying and addressing renal risk factors before HAART is initiated could minimize therapy-associated renal toxicity

  • The renal function of patients treated with HAART should be monitored at each medical consultation

  • Fear of possible nephrotoxic effects is not a valid reason to withhold life-saving HAART

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Figure 1: Flowchart for diagnosis of renal symptoms in patients on highly active antiretroviral therapy.
Figure 2: Proposed mechanism of tenofovir processing by proximal tubule cells through active tubular secretion in the absence a | or in the presence b | of probenecid and ritonavir.

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Authors and Affiliations

  1. Department of Nephrology, La Pitié-Salpêtrière Hospital, Paris, France

    Hassane Izzedine

  2. AIDS Research Programme, St Paul's Hospital, Providence Healthcare, Vancouver, BC, Canada

    Marianne Harris

  3. Department of Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA

    Mark A. Perazella

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Izzedine, H., Harris, M. & Perazella, M. The nephrotoxic effects of HAART. Nat Rev Nephrol 5, 563–573 (2009). https://doi.org/10.1038/nrneph.2009.142

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