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.
Highlights
The nephron is the functional unit of the kidney and consists of a continuous tube of highly specialized heteroge-neous cells
The organic anion transporters in the basolateral membrane are responsible for the active transportation of tenofovir into renal proximal tubule cells [4,5], subsequently the drug is secreted to the tubular lumen by the apical membrane transporters [6]
In our previous study we evaluated tenofovir associated renal toxicity with emphasis on cohorts, clinical studies and its reversibility
Summary
Some drug substances are actively transported across the renal proximal tubule by drug transporters followed by elimination via the urine which is a major pathway in the detoxification process [2]. Some of these eliminated drugs are toxic and their contact with drug transporters in tubular cells is the first fundamental stage in the development of their nephrotoxic process. Due to tenofovir reported renal toxicity, in our initial study—Part one, we critically looked at cohorts and clinical studies In this second part, we are evaluated case reports, genetic factors, pharmacology of tenofovir renal toxicity and the implications of drug-drug interactions on tenofovir renal toxicity
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