Tenofovir-induced acute renal failure in an HIV patient with normal renal function

Sir,

Tenofovir is a nucleotide reverse transcriptase inhibitor widely used to treat HIV infection. Some cases of acute tubular necrosis and Fanconi's syndrome have been reported, but the drug is usually not considered as nephrotoxic. We would like to report here a first case presenting as acute renal failure related to tenofovir, leading to chronic dialysis.

Case. A 39-year-old white man, with an HIV infection diagnosed in 1999, was admitted in June 2003 with acute renal failure. Two months prior to admission his renal function was normal, with a serum creatinine of 0.81 mg/dl (72 µM) and a creatinine clearance of 100 ml/min. HIV infection was asymptomatic with a CDC classification of A2, and he was treated with lamivudine, zidovudine and nevirapine. In May 2003, as his viral load increased and the CD4 count fell, the treatment was changed to tenofovir (245 mg/day), didanosine (250 mg/day) and abacavir (600 mg/day). Two weeks later, the patient had an episode of vomiting. His serum creatinine was 2.67 mg/dl (237 µmol/l). Because of deteriorating renal function, he was admitted to hospital 1 week later.

Physical examination showed a well-hydrated and normotensive man. He was oliguric and had no rash.

Laboratory data showed renal failure (blood urea nitrogen 80 mg/dl, creatinine 11.7 mg/dl) and metabolic acidosis (bicarbonate 11 mmol/l). Electrolytes, liver tests and blood formula were within the normal range without hyper-eosinophilia. The urinalysis revealed proteinuria (1 g/day), haematuria (27 cells/µl), leukocyturia (291 cells/µl), no crystals and some peeled epithelial cells. The fractional excretion of sodium was 4%.

Renal ultrasound was normal and renal histology revealed a typical aspect of acute tubular necrosis with vacuolation of the proximal tubular cells and no evidence of focal or global glomerulosclerosis.

The antiretroviral treatment was withheld and intermittent haemodialysis was started. Despite optimal hydration, renal function did not improve. One year later, he is now on peritoneal dialysis with a viral load of 50 copies/ml and a CD4 count of 350 cells/mm3. His actual antiretroviral treatment is stavudine, didanosine and nelfinavir.

Comment. This patient had no other cause of acute renal failure and the chronology strongly suggests the imputability of tenofovir. Indeed, abacavir has only been responsible for acute renal failure associated with hypersensitivity reaction [1] and no pharmacokinetics interaction that could lead to drug accumulation or enhanced toxicity was identified.

Until recently, the renal tolerance of tenofovir, ≤300 mg/day, was considered excellent. Occasional reports of Fanconi's syndrome (0–3%) or renal failure have been mentioned in survey studies (tenofovir studies GS-00–902 and GS-00–907, Gilead Sciences, 2000) with a similar incidence of renal dysfunction in the placebo groups. In the literature, only five case reports of tenofovir-induced tubular necrosis have been published and serum creatinine improved in all cases after drug cessation [2–5].

This report highlights the nephrotoxicity of tenofovir, which can be severe enough to lead to end-stage renal disease and to require chronic dialysis. Practitioners should be aware of this potential adverse reaction and monitor renal function closely, particularly at the start of the treatment, even in patients with normal renal function.

Conflict of interest statement. None declared.

Thierry Krummel1, Laura Parvez-Braun1, Luc Frantzen1, Henri Lalanne2, Luc Marcellin3, Thierry Hannedouche1 and Bruno Moulin1

1 Department of Nephrology2 Department of Internal Medicine3 Department of Pathology University Hospital of Strasbourg France Email: Thierry.Krummel{at}chru-strasbourg.fr

References

  1. Krishnan M, Nair R, Haas M, Atta MG. Acute renal failure in an HIV-positive 50-year-old man. Am J Kidney Dis 2000; 36: 1075–1078[ISI][Medline]
  2. Karras A, Lafaurie M, Furco A et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis 2003; 36: 1070–1073[CrossRef][ISI][Medline]
  3. Coca S, Perazella MA. Acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. Am J Med Sci 2002; 324: 342–344[CrossRef][ISI][Medline]
  4. Creput C, Gonzalez-Canali G, Hill G, Piketty C, Kazatchkine M, Nochy D. Renal lesions in HIV-1-positive patient treated with tenofovir. Aids 2003; 17: 935–937[CrossRef][ISI][Medline]
  5. Schaaf B, Aries SP, Kramme E, Steinhoff J, Dalhoff K. Acute renal failure associated with tenofovir treatment in a patient with acquired immunodeficiency syndrome. Clin Infect Dis 2003; 37: e41–e43[CrossRef][ISI][Medline]