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

Abstract

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.

Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

“… 2 , 3 In many studies, treatment with TDF was associated with kidney tubular dysfunction and reduced renal function, with higher prevalence being associated with female gender and age between 40 and 50 years. 4 , 5 , 6 The main target of toxicity is the proximal renal tubule, and in severe cases patients developed renal Fanconi syndrome. 7 Studies have shown that albuminuria might be a more reliable marker for glomerular and proximal tubular dysfunction.…”

“… 8 The effect of TFV on glomerular function is less severe than renal tubular function. 6 TFV nephrotoxicity leads to break down of solute transport characterised by urine wasting of solutes and proteins such as albumin normally reabsorbed in the proximal tubule. 7 Genetic polymorphisms in proximal tubule transporters may predispose certain individuals to accumulate high intracellular TFV levels and could increase the risk of developing proximal tubular toxicity.…”

Impact of Co-administered Lopinavir/Ritonavir and Sulfamethoxazole/Trimethoprim on Reproductive Indices of Male Albino Rats

“…Lopinavir is usually boosted with ritonavir to increase its pharmacological profile. In the management of HIV/AIDS lopinavir/ritonavir is used as a combination therapy with other antiretroviral drugs [12,13,14,15]. Lopinavir/ritonavir mediates its antiviral activity by binding the protease enzyme, and preventing the cleavage of the gag and gag/pol polyproteins into structural functional proteins and enzymes thereby preventing the formation of new viral particles [16].…”

Maternal and infant renal safety following tenofovir disoproxil fumarate exposure during pregnancy in a randomized control trial

“…Since its approval by the US Food and Drug Administration (FDA) in 2001, tenofovir disoproxil fumarate (TDF) has been in clinical use as treatment for HIV-1 infection in combination with other antiretroviral (ARV) drugs, pre-exposure prophylaxis (PrEP) for prevention of sexually acquired HIV-1 infection, and treatment of chronic hepatitis B virus (HBV) infection [ 1 , 2 ]. Because TDF has a favorable potency, tolerability, and pharmacokinetic profile that allows for daily dosing, it is one of the most commonly used ARVs in adolescents and adults [ 3 ].…”