Tenofovir Renal Toxicity: Evaluation of Cohorts and Clinical Studies—Part One

Abstract

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