Case report of kidney lesions in HIV-positive man treated with tenofovir

In the April edition of AIDS French doctors report a case of kidney lesions in a 60 year old HIV-positive man treated with a HAART regimen including tenofovir. The case report adds to the growing body of evidence that kidney toxicity - specifically, proximal tubular dysfunction - is a rare side-effect of tenofovir.

The case concerned a 60 year-old white, gay man who had been living with diagnosed HIV infection for 13 years. He had been extensively pre-treated with antiretroviral drugs and was on his sixth regimen, which included tenofovir, ddI and d4T, adding atazanavir and ritonavir after 15 days. When this treatment was started his viral load was 4.04 log₁₀ copies/ml, CD4 cell count 318 cells/mm³ and serum creatinine level, a measure of kidney function, was 72 micromol/l (0.8mg/dL).

After four weeks of treatment the patient developed acute renal failure. Protein and blood were detected in his urine (proteinuria and haematuria) and his serum creatinine level increased to 351 micromol/l (3.9mg/dL). There was no fever or evidence of infection.

Fanconi’s syndrome was diagnosed. The syndrome is a disorder of the proximal renal tubes of the kidneys, involving an inability to reabsorb electrolyes and nutrients back into the body. Fanconi's syndrome can be used by nucleotide analogue damage to the mitochondria in the proximal renal tubes.

A kidney biopsy revealed that lesions were present in proximal convoluted tubes.

All anti-HIV medication was stopped and serum creatinine levels stabilised at 200 micromol/l (2.2mg/dL) for two months.

Tenofovir acts on the proximal tubular cells, affecting clearance of the drug. This is also the case with the anti-hepatitis B drug adefovir which was originally developed as an HIV treatment but was abandoned as the dose required to treat HIV (but not hepatitis B) caused kidney toxicities.

The investigators recommend that people taking tenofovir are screened for proximal dysfunction and have their creatinine levels checked regularly.

Monitoring for kidney toxicity on tenofovir: recent expert discussion

A recently published discussion between US experts has highlighted issues to consider in relation to tenofovir kidney toxicity. Published at the new Clinical Care Options for HIV website, the discussion between Edward Acosta (University of Alabama at Birmingham), Stephen Becker (University of Califonia, San Francisco) and Courtney Fletcher (University of Colorado) highlights a number of key issues:

• Certain types of patients are likely to be predisposed, especially those that have had any prior exposure to a nephrotoxic drug, whether it be adefovir or amphotericin.
• Some patients reported to have experienced kidney toxicity had creatinine levels and creatinine clearance at the upper limit of normal; current tenofovir labelling recommends that individuals with creatinine levels greater than 1.5mg/dL (132 micromol/l) should not commence tenofovir treatment.
• It is probably better to assess creatinine clearance rather than serum creatinine, since the latter may not reflect the adequacy of clearance in patients with more advanced disease who may not have a great deal of muscle mass.

Further information on this website

Tenofovir - overview

Adefovir - overview

First report of tenofovir kidney toxicity - news story

Additional reports of tenofovir kidney toxicity - news story

The kidneys - factsheet