Tenofovir is one of the most commonly used antiretrovirals in adolescents and adults because of its potency and favorable pharmacokinetic and relative safety toxicological profile. It has been combined successfully with antiretroviral drugs from classes such as protease inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors to achieve virologic suppression in a high percentage of recipients. Despite its therapeutic success, quite a number of cohorts and clinical studies have associated tenofovir with the development of renal toxicity with few studies on the opposing end. This stimulated us to review reported cohorts and clinical studies on tenofovir renal toxicity. In this study it was observed that literature reported incidence of tenofovir renal toxicity falls within the range of 0.7% -17%. Available studies gave different appellations to tenofovir renaltoxicity, which include fanconis syndrome, proximal tubule dysfunction, acute renal failure, chronic renal failure, chronic kidney disease and nephrogenic diabetes insipidus. Markers of renal toxicity (tubulopathy) which include glycosuria, hyperaminoaciduria, proteinuria, hyperphosphaturia, hyperuricosuria, retinol-binding protein, beta2-microglobulinuria, decreased creatinine clearance and decreased glomerular filtration rate were also reported. In some studies renal biopsy demonstrated cytoplasmic vacuolization, apical localization of nuclei and reduction of the brush border on proximal tubule epithelial cells. This study observed that tenofovir renal toxicity could be reversible on discontinuation of tenofovir therapy despite contrary views by some studies. Regardless of tenofovir reported renal toxicity, it is well tolerated with a relative safety profile but it is advised that renal profile of patients should be evaluated before and routinely during tenofovir therapy.

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.