Case of Fanconi syndrome caused by ddI reported

A case of severe kidney toxicity associated with ddI therapy has been reported in the May 20^th edition of AIDS.

It is well known that ddI can cause side-effects including peripheral neuropathy, lactic acidosis and hepatitis. However, only one case of kidney failure associated with ddI treatment has been previously published.

Doctors in Paris, however, reported a case of Fanconi syndrome involving a 32 year old gay man diagnosed with HIV 16 years previously. He started antiretroviral therapy in 1997 with a regimen including the protease inhibitor indinavir that can cause kidney problems, and was diagnosed with hepatitis B virus in 2002, which was being treated with 10mg adefovir a day.

In the summer of 2004 he was hospitalised after he reported fatigue, dehydration, weight loss and blood in his urine. Although he was drinking between four and five litres of water a day he reported a dry mouth. At the time of his hospitalisation his CD4 cell count was 87 cells/mm³ and his viral load was 13,000 copies/ml. The investigators do not provide details of the individual’s anti-HIV treatment at this time, other than he was taking ddI.

On examination doctors found that he had high blood pressure and a racing pulse. There was no clinical evidence of inflammation or infection. Laboratory analysis indicated high lactate levels, a blood phosphate level of 0.54mmol/l, and a creatine clearance of 66ml/min. Urine output on the second day of hospitalisation was 4.5 litres with glucose and blood present.

A renal biopsy which yielded results consisted with Fanconi syndrome was performed .

Although high-dose adefovir can cause kidney toxicities, the 10mg daily dose does not have this side-effect profile. Doctors therefore concluded that the patient had developed Fanconi syndrome caused by ddI.

Consequently the treatment with ddI was discontinued but therapy with adefovir was continued. One month later the man’s general health had improved with urine output decreasing to two litres daily. Blood pressure had also stabilised and the patient’s peripheral neuropathy had improved. Creatinine clearance was 80ml/min and plasma potassium and uric acid had normalised. There was no longer sugar in the man’s urine and the level of protein was falling.

“Our patient’s clinical and biological characteristics are consistent with those of Fanconi syndrome”, write the investigators. They conclude “ddI must be added to the list of antiviral drugs that can induce Fanconi syndrome, which includes tenofovir, cidofovir and high-dose adefovir and foscarnet.”