Improved immunological profile of HIV infected patients with renal abnormalities on antiretroviral therapy

Abstract

The kidneys can be susceptible to antiretroviral drug toxicity because of their layout and function. A growing number of cross sectional reports and longitudinal studies have described an association between treatment with antiretroviral therapy and proximal tubular dysfunction or impaired glomerular filtration rate (GFR) in patients with human immunodeficiency virus (HIV) infection.1, 2 Alterations on tenofovir secretion by proximal renal tubule may lead directly to a greater drug accumulation in the renal tubular cells and, consequently lead to proximal tubular damage and renal toxicity.3,4 Several studies have found that CKD is associated with increased mortality among HIV-infected individuals.5 Studies of TDF toxicity suggested that mitochondria were unlikely to be the targets.6 Studies by Hall et al.7 have consistently observed marked ultrastructural abnormalities in mitochondria in the proximal tubule in cases of TDF-induced Fanconi syndrome. Further evidence in support of the fact that mitochondria are the major targets of TDF toxicity in the kidney has been provided by 2 recent rodent studies.8−10 However, the animals were exposed to about twice the normal dose in humans when adjusted for body weight.9 Interactions with other nephrotoxic agents and/or underlying genetic polymorphisms in transporters might help explain why TDF accumulates in proximal tubule cells in some patients, but do not shed further light on the exact intracellular targets of toxicity.11 Finally, there is evidence that TDF is specifically toxic to mitochondria in the proximal tubule, and the exact mechanisms of this damage remain unknown till date.