Treatment with the nucleotide analogue tenofovir (Viread) is associated with mild kidney toxicity, according to a German study published in January 3rd edition of AIDS. The study investigators note that the mild kidney dysfunction resulting from therapy with tenofovir could make the kidneys more vulnerable to side-effects from other drugs causing kidney toxicities.
Tenofovir shares some of its molecular structure with adefovir, another nucleotide analogue which was originally investigated as a treatment for HIV. However was not pursued as a treatment for HIV after clinical trials showed that the dose of adefovir needed for HIV therapy caused renal failure and Fanconi’s syndrome. A lower dose of adefovir which is not toxic to the kidneys is used as a treatment for hepatitis B.
Clinical trials leading to the licensing of tenofovir as an HIV therapy did not find a higher incidence of kidney dysfunction, however since the drug’s approval there have been anecdotal reports of kidney dysfunction in people taking tenofovir, although investigators found in many cases that preexisting kidney problems were the cause.
German investigators conducted a cross-sectional study to assess the effects of tenofovir on glomerular and tubular renal function. A total of 82 patients taking tenofovir and 92 patients who were taking HAART, but not tenofovir, were recruited to the study.
Glomerular kidney function was assessed by measuring creatine in urine or cystatin C in serum (glomerular filtration rate). Tubular renal function was measured by looking at protein in urine.
Patients taking tenofovir had lower creatine clearance and lower cystatin clearance (both p
In addition, patients taking tenofovir had higher mean protein in urine (124mg/day versus 94mg/day, p = 0.03), and 30% of individuals taking tenofovir versus only 5% of patients not taking the drug had protein in urine greater than 130mg/day (p
“Treatment with tenofovir was associated with a lower mean glomerular filtration rate”, conclude the investigators, adding that patients treated with tenofovir were also significantly more likely to have protein in their urine.
However, the investigators note that the kidney dysfunction noted in their study was mild. Although impaired, the mean glomerular filtration rate in the tenofovir-treated patients was still within the normal range. Furthermore, in contrast to tenofovir, the tubular dysfunction caused by tenofovir did not result in enhanced renal loss of electrolytes.
“Treatment with tenofovir may induce mild renal dysfunction in a higher proportion of patients compared with patients never treated with tenofovir. Treatment with tenofovir may render the kidney more vulnerable to concomitant treatment with nephrotoxic drugs”, conclude the investigators.
Mauss S et al. Antiretroviral therapy with tenofovir is associated with mild renal dysfunction. AIDS 19: 93 – 99, 2005.