Proximal tubular dysfunction associated with tenofovir in an HVC-HIV co-infected patient undergoing HVC therapy

Sir, Tenofovir is an adenosine analogue, and exposure to ribavirin (RBV) could increase the intracellular phosphorylated metabolities of tenofovir. Nucleoside analogues essentially have mitochondrial toxicity. Nephrotoxicity of these nucleoside analogues in combination with HVC therapy is a rare complication [1]. We present the case of a 40-year-old white man, with HIV infection diagnosed in 2001 and VHC in 2006. The HIV infection was asymptomatic with a CD4+ lymphocyte count of 711 cells/μl and undetectable plasma HIV-RNA. The antiretroviral treatment was efavirenz (600 mg/day), emtricitabine (200 mg/day) and tenofovir disoproxil fumarate (300 mg/day). In November 2006, the patient initiated therapy for the VHC infection consisting of pegylated interferon and RBV therapy. The renal function was normal, with a serum creatinine of 86 μmol/l and a creatinine clearance of 100 ml/min/1.73 m2. Five months after initiation of treatment for the VHC infection, the patient showed general weakness and dyspnea. Blood and urine analyses on admission indicated the presence of anaemia (haemoglobin 6.4 g/dl and haematocrit 20.6%), renal failure (creatinine of 424 μmol/l, urea 10.7 mmol/l, MDRD 12.3 ml/min/1.73 m2 and proteinuria 1.13 g/24 h) and proximal tubular kidney dysfunction with hypophosphataemia, hypouricaemia, hyperchloraemic metabolic acidosis with normal anion gap and a low-molecular-weight proteinuria. A renal biopsy showed the presence of chronic tubulo-interstitial lesions and focal-segmental glomerulosclerosis (Figure ​(Figure11). Fig. 1 Optical microscopy. Hematoxilin-eosine. 100×: chronic tubulo-interstitial damage with some inflammation, and segmental sclerotic lesion in one glomerulus. The patient was diagnosed with HIV nephropathy and proximal tubular dysfunction secondary to tenofovir and RBV treatment. The administration of these drugs was stopped. Two months later the metabolic disorders completely regressed with partial recovery of renal function (creatinine of 186 μmol/l and MDRD of 37 ml/min/1.73 m2) and reduction of proteinuria (0.40 g/24 h). Some cases of acute tubular necrosis, isolated tubular defects such as Fanconi syndrome, distal tubular acidosis and nephrogenic diabetes insipidus, have been reported with reverse transcriptase inhibitors [2]. Tenofovir is eliminated by glomerular filtration and active tubular secretion. Hypothetically, this effect could enhance the risk of kidney tubular dysfunction in HVC-HIV co-infected patients undergoing HVC therapy, although tenofovir-related nephrotoxicity is apparently rare and mainly seen in patients with mild pre-existing renal impairment [3,4]. In the same manner as other reverse transcriptase inhibitors, RBV could compete with tenofovir for the human organic anion transporter-1 (hOAT1), on the basolateral membrane of the proximal tubules, resulting in an increased tenofovir concentration and tubular toxicity [1,5]. Conflict of interest statement. None declared.