Néphrotoxicité du ténofovir

Abstract

Tenofovir is currently the only commercially available nucleotidic reverse-transcriptase inhibitor of human immunodeficiency virus (HIV). It is overall very well tolerated and is prescribed to millions of patients–without any specific monitoring in developing countries. However a significant nephrotoxicity has been described. Acute nephrotoxicity is well characterized. Tenofovir is excreted in urine by proximal tubular epithelial cells. In case of cytoplasmic accumulation, tenofovir inhibits mitochondrial DNA polymerase γ, which causes a dysfunction of the respiratory chain, and in turn an alteration of the energy-deprived cells. Fanconi syndrome is the clinical expression of tenofovir acute toxicity, with sometimes an associated acute kidney failure. These abnormalities are usually reversible, at least partially, when tenofovir is discontinued. Tenofovir chronic toxicity has been debated but seems now well established by several cohort studies, even though it pathophysiology has yet to be understood. It manifests as an accelerated glomerular filtration rate decline in treated patients with no other renal abnormalities. The identification of this chronic toxicity was probably blurred by multiple cofactors, usually excluded from clinical trials. Simple measures such as dose adaptation to kidney function, identification of risk factors, and plasmatic tenofovir concentration monitoring can help decrease the risk of nephrotoxicity.