First report of tenofovir kidney toxicity

French researchers have reported a case of kidney failure and Fanconi syndrome attributable to tenofovir treatment. Although kidney toxicity is a well established side effect of tenofovir’s sister drugs adefovir and cidofovir, it has not previously been reported as a consequence of tenofovir treatment.

Although pre-clinical animal studies showed that high doses of tenofovir could cause kidney failure, large scale licensing studies in humans produced no evidence of kidney toxicity. Nevertheless, there has been concern among clinicians that this side-effect remains a possibility.

The case occurred in a 45 year old woman with HIV and HCV co-infection, who developed acute renal failure and Fanconi syndrome five months after introducing tenofovir to her anti-HIV regimen. At the time she was also taking ddI, lopinavir/ritonavir, cotrimoxazole, fluconazole, omeprazole, valproid acid and methadone, all of which were discounted by researchers as a cause of kidney failure.

The toxicity is likely to be a consequence of the effect of tenofovir on particular cells in the kidneys. Although tenofovir has been shown to have very low levels of mitochondrial toxicity in kidney cells, even when dosed far above the recommended level, the authors argue that tenofovir is most likely to have been responsible for the problems due to the specific presentation. Fanconi syndrome, they note, has not been a feature of any of the cases of acute renal failure or dysfunction reported with other drugs taken by the patient.

Fanconi syndrome is a disruption of the normal filtering processes that take place in the tubes of the kidneys, which are supposed to reabsorb substances like glucose, potassium, bicarbonate and calcium before they are excreted in urine. Eventually the syndrome results in bone disease due to lack of essential substances like calcium, as well as fractures. In this case, Fanconi syndrome was also associated with the onset of nephrogenic diabetes insipidus, a condition in which the kidneys fail to return water to the blood and excrete it as very dilute urine, leading to severe dehydration.

The temporal relationship between tenofovir treatment, the onset of kidney failure and the normalisation of serum creatinine levels is also suggestive, the authors say. Serum creatinine levels had returned to normal (1.3mg/dL) within four weeks of stopping the drug, and were still at this level eight weeks later. Renal function, Fanconi syndrome and diabetes insipidus all improved rapidly after ceasing tenofovir.

Although this case report does not imply that kidney disease will become a widespread problem for people receiving tenofovir treatment, the authors emphasise the importance of regular monitoring of serum creatinine and electrolytes in patients receiving tenofovir. Anyone on tenofovir who begins to experience symptoms of extreme thirst, frequent urination, confusion or muscular weakness should report these symptoms to their doctor immediately.