TITLE:
Tenofovir Renal Toxicity: Evaluation of Cohorts and Clinical Studies—Part 2
AUTHORS:
Adikwu Elias, Ogbuehi Ijeoma, Nkereuwen Jonathan Edikpo, Deo Oputiri, Oru-Bo Precious Geoffrey
KEYWORDS:
Tenofovir; Renal; Toxicity; Interactions; Polymorphism; Pharmacology
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.1,
January
23,
2014
ABSTRACT: Tenofovir is a nucleotide reverse transcriptase inhibitor used as part of
antiretroviral regimens. It is well tolerated with relative toxicological
effects but recent reports have linked it with renal toxicity which is of
clinical concern. This study reviews literary work on tenofovir renal toxicity
with more light on case reports. Tenofovir renal toxicity manifests as
Fanconi’s syndrome, nephrogenic diabetes insipidus and acute renal failure.
Fanconi’s syndrome is characterised by acidosis, protenuria, albuminuria, aminoaciduria,
hyperchloremic, metabolic acidosis, hypouricemia, hypophosphatemia and
glycosuria. The presence of urine osmolality, polydipsia
and polyuria could give credence totenofovir induced nephrogenic diabetes
insipidus. In some cases of tenofovir renal toxicity, renal biopsy revealed
sclerosed glomeruli with ischemic injury including portal collapse of capillary
loops. Histopathological changes in glumeruli include mild mesangial proliferation, increased mesangial matrix and thickened
capillary loops. Moderate degenerative tubular changes, loss of tubular mass, interstitial
scarring and scattered cellular infiltrates. Pharmacodynamic and
pharmacokinetic interactions may occur with the co administration of tenofovir
with non steroidal anti-inflammatory drugs, aminoglycosides and some protease inhibitors
which may potentiate renal toxicity. Tenofovir renal toxicity is associated
with some risk factors including genetic polymorphism as supported by dichotomy
in renal toxicity among different race and the association between ABCC2 gene and tenofovir kidney tubular
dysfunction. The pharmacology of tenofovir renal toxicity is unclear but it is
attributed to the interaction between tenofovir and theorganic anion
transporters (hOAT1, and to a lesser extent, OAT3) favoring intracellular accumulation in renal proximal tubule cells. This
may lead to ultrastructural mitochondrial abnormalities
and decreased mtDNA levels which could stimulate reactive oxygen species production, depletion of antioxidants and
antioxidant enzymes. These processes can stimulate the destruction of biomolecules such as DNA,
proteins, and lipids, thus causing the deregulation of redox-sensitive
metabolic pathways,
signaling pathways, and cell death. Despite tenofovir renal toxicity it has
achieved notable therapeutic success nevertheless patients on tenofovir
containing regimens should be monitored for renal function parameters. Co administration
with potential nephrotoxic drugs should be avoided except when benefit outweighs
risk.