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Tenofovir-related renal dysfunction can’t always be reversed

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Tenofovir nephrotoxicity can’t always be fully reversed in HIV-infected men, according to a new study.

Up to 2% of patients have adverse renal effects from the nucleotide reverse transcriptase inhibitor, and reportedly, kidney function rapidly normalizes when tenofovir is stopped. But “because of the few cases, limited follow-up and the insensitive measure used” (serum creatinine) in the previous reports, it’s not known how reversible the nephrotoxicity really is, note senior author Dr. Andrew Carr, from St. Vincent’s Hospital, Sydney, Australia, and colleagues.

In a paper published online February 19th in the Journal of Acquired Immune Deficiency Syndromes, Dr. Carr and his associates describe 24 men who discontinued tenofovir because their estimated glomerular filtration rate (eGFR) was less than 60 ml/minute/1.73 m2.

During a median of 30 months between start of tenofovir and drug cessation, median eGFR fell from 74 to 51 ml/min/1.73 m2 – a reduction about 10 times greater than expected with normal aging.

During the median period of 13 months after tenofovir discontinuation, eGFR rose by a median of 19 ml/min/1.73 m2. Most improvement occurred in the first month.

In only 10 (42%) patients did eGFR return to pre-tenofovir levels, and only two exceeded 90 ml/min/1.73 m2.

Twelve patients had eGFR increases above the median; this group had a more rapid monthly decline while on tenofovir compared to those with less improvement (1.9 vs 0.7 ml/min/1.73 m2, p = 0.009) and a shorter duration of tenofovir therapy (21 vs 51 months, p = 0.08), suggesting that “more acute renal damage is less likely to be permanent.”

These patients were also more likely to have received protease inhibitors (100% vs 54%, p = 0.02). The authors explain that protease inhibitors can increase tenofovir levels in plasma and renal tubular epithelium. Therefore, the greater improvement was likely due to cessation of higher tenofovir exposure.

The single-center study was retrospective, relatively small and had a variable duration of follow-up, and so prospective validation in a larger, more heterogeneous population is needed, the researchers say.

Nevertheless, they conclude, earlier discontinuation of tenofovir might have led to greater improvements in renal function, “which underlines the importance of regular assessment and perhaps of earlier intervention.”

Specifically, they advise, even gradual deterioration in eGFR to levels above 60 ml/min/1.73 m2 might be cause enough to discontinue tenofovir.

Reference:
J Acquir Immune Defic Syndr 2010.