Doctors from the Hopital Saint-Loius in Paris report three cases of tenofovir related kidney toxicity in the 15thApril 2003 edition of Clinical Infectious Diseases. There have now been several reports of tenofovir-related renal toxicity (see link below for aidsmap news stories).
All three patients treated at the Hopital Saint-Louis had chronic HIV infection and had been treated with earlier HAART regimens before starting a regimen containing tenofovir. None of the other drugs the patients were prescribed had renal toxicity as a recognised side-effect and all the patients had normal kidney function.
A slight increase in serum creatinine levels (under 1.6mg/dl) in all three patients was observed after a few weeks of tenofovir therapy, but treatment was not interrupted at this time.
After several months taking tenofovir two patients required hospitalisation because of a rapid decline in renal function. One patient had a peak creatinine level of 7.80mg/dl, the other of 2.71mg/dl. Renal failure could not be attributed to the use of other medication or to infection. Kidney biopsy indicated that there was severe acute tubular necrosis.
Discontinuation of HAART was associated with rapid improvement in kidney function, although serum creatinine levels remained elevated (2.14mg/dl in one patient and 1.69mg/dl in the other) suggesting partially irreversible kidney damage to the treating physicians.
Anti-HIV therapy, minus tenofovir, was restarted a few weeks later, with no new increases in creatinine level or recurrences of tubular dysfunction.
In the third patient, tenofovir use was associated with daily urine output above six litres (severe polyuro-polydipsic syndrome). Protein was also detected in urine. Within three weeks of tenofovir therapy being stopped, there was no sign of kidney toxicity. Doctors believe that this case demonstrated that tenofovir is potentially toxic not only to the proximal tubes, but also to the epithelial cells in the kidney’s collecting duct.
However, the doctors are unclear why tenofovir caused renal toxicity in their three patients. They speculate that as tenofovir is excreted by the kidneys, a drug or drugs which interfere with renal excretion may have caused a build-up of tenofovir and be responsible. Lopinavir-ritonavir (Kaletra) has been shown to increase plasma concentrations of tenofovir by up to 30% and the doctors note that two patients were treated with this antiretroviral.
The Parisian doctors conclude by stressing that: “Patients receiving tenofovir must be monitored closely for early signs of tubulopathy…even several months after the initiation of treatment; if there are signs of tubulopathy, therapy should be stopped as soon as possible to avoid the risk of definitive renal failure."
Further information on this website
Tenofovir - Overview
First report of tenofovir kidney toxicity - News story
Additional reports of tenofovir kidney toxicity - News story
Case report of kidney lesions in HIV-positive man treated with tenofovir - News story
The kidneys - Factsheet
Karras A et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetes inspididus. Clinical Infectious Diseases, 36 (on-line edition), 2003.