The role of drug interactions and monitoring in the prevention of tenofovir-associated kidney disease.

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Abstract
To The Editor—Zimmerman et al. [1] described 5 patients and reviewed 22 published cases of tenofovir-associated renal injury, emphasizing the potential role of drug interactions, incomplete recovery of renal function that occurred in some cases, and intensive monitoring of kidney function. Increased exposure to tenofovir occurs when the combination of lopinavir-ritonavir or atazanavir is coadministered [2]. The statement that ritonavir causes tenofovir to accumulate in renal tubules because of inhibition of multidrug resistance protein (MRP) 2—mediated efflux is not supported by experimental evidence. Recent studies have demonstrated that another renal transporter, MRP-4, is responsible for the efflux of tenofovir, and this process is not diminished by protease inhibitors [3]. Concurrent use of lopinavir-ritonavir, didanosine, or atazanavir occurred often in their report, but analysis of an appropriate control population is necessary for one to infer meaningful associations. Although lopinavir-ritonavir use may contribute directly to toxicity, use of this agent also may be a marker of patients who have a higher risk of adverse events associated with use of multiple medications due to advanced disease. In an analysis of patients treated with tenofovir, lopinavir-ritonavir use was not associated with diminished glomerular filtration rate after controlling for other clinical variables [4].