Tenofovir disoproxil fumarate and the kidney in HIV-infected patients: the evidence thus far.

Tenofovir disoproxil fumarate (TDF) is an integral part of the initial treatment regimen for HIV and a subgroup of hepatitis B coinfected patients, after its safety and efficacy were demonstrated in a number of prospective studies. However, concerns still remain regarding its potential for kidney injury. The nature of kidney involvement is variable, with various phenotypes reported in different studies. Proximal kidney tubular dysfunction (PKTD) has been reported as one of the commonly recurring phenotypes from most studies. The exact mechanism of TDF-induced PKTD is unknown, but it has been suggested to be due to a combination of functional polymorphisms in the genes that encode efflux transporter proteins and raised proximal tubular cell concentrations of TDF, resulting in oxidative stress and mitochondrial dysfunction. Gaps still remain in our understanding of this novel concept of TDF-induced kidney toxicity, and conflicting observations are made with accumulating evidence. For instance, whether HIV p...