Tenofovir-induced nephrotoxicity: incidence, mechanism, risk factors, prognosis and proposed agents for prevention

In this study, data regarding epidemiology, risk factors, pathogenesis and outcome of tenofovir-induced nephrotoxicity will be reviewed, and current and future approaches for prevention will be discussed. The data were collected by searching Scopus, PubMed, Medline, Science direct, Clinical trials and Cochrane database systematic reviews. The keywords used as search terms were "Tenofovir", "TDF", "NRTI", "Nephrotoxicity", "Renal failure", "Kidney damage", "HIV" and "AIDS". Several predisposing factors including elevated baseline SCr, concomitant nephrotoxic medications, low body weight, advanced age, tenofovir disoproxil fumarate (TDF) dose and duration of treatment and lower CD4 cell count were identified as risk factors for development of TDF-induced nephrotoxicity. Cellular accumulation through increased entry from the human organic anion transporters and decreased efflux into tubular lumen is main mechanism of nucleotide analogue antiviral induced nephrotoxicity. Renal function assessment and monitoring at baseline and during TDF treatment are the main approach of prevention of TDF-induced nephrotoxicity. Rosiglitazone may be helpful in patients presenting with TDF-induced nephrotoxicity. Pretreatment with melatonin prevented all known histological changes in proximal tubular mitochondira induced by TDF. Use of antioxidants with mitochondria-targeted properties such as MitoQ or Mito-CP may prevent proximal tubular mitochondrial against TDF damage. Vitamin E, ebselen, lipoic acid, plastoquinone, nitroxides, SOD enzyme mimetics, Szeto-Schiller (SS) peptides, and quercetin are other potential agents for prevention of TDF-induced nephrotoxicity. However, data regarding effectiveness of nephroprotective agents against TDF-induced nephrotoxicity are not conclusive. Before extrapolation of the preclinical evidence to clinical practice, these evidence should be confirmed in future human studies.