Tenofovir, a new nucleotide reverse transcriptase inhibitor that has good antiviral activity against drug-resistant strains of HIV, is structurally similar to cidofovir and adefovir and seems to be less nephrotoxic. Nephrotoxicity of cidofovir and adefovir is well established and they have been associated with increase for acute renal insufficiency due to tubular toxicity, possibly induced via mitochondrial deplection. Tenofovir has little mithocondrial toxicity in in vitro assays and early clinical studies. However some cases of renal tubular dysfuntion and renal failure related to tenofovir treatment have been published recently. Increased plasma concentrations of didanosine were observed after the adition of tenofovir and protease inhibitors can interact with the renal transport of organic anions leading to proximal tubular intracellular accumulation of tenofovir, yield Fanconi syndrome-type tubulopathy. We present a case in wich acute renal failure and proximal tubular dysfunction developed after therapy with tenofovir in a patiente with HIV who had suffered from complications of didanosine treatment. Although nephrotoxicity certainly occurs much less frequently with tenofovir that it does with other nuclotide analogues, use of tenofovir by patients with underlying renal disfuntion, for longer durations and/or associated with didanosine or lopinavir-ritonavir, might be associated with renal toxicity. Patients receiving tenofovir must be monitored for sings of tubulopathy with simple tests such us glycosuria, phosphaturia, proteinuria, phosphoremia and renal function, as well as assessment for signs of mithocondrial toxicity when a nucleoside analogue is being administered, and therapy should be stopped to avoid the risk of definitive renal failure.