CATIE News - Are high tenofovir levels linked to kidney damage?
The anti-HIV drug tenofovir (Viread) is available in fixed-dose combinations with other drugs and sold under these brand names:
- Truvada (tenofovir + FTC)
- Atripla (tenofovir + FTC + efavirenz)
Tenofovir has antiviral activity against HIV and hepatitis B. In general, tenofovir is well tolerated and an effective part of HIV treatment regimens. As a result, it is a popular choice.
Tenofovir is removed from the blood by the kidneys. The kidneys can do this because there are small transporter proteins that help move tenofovir from the blood. There have been reports of kidney dysfunction and, in rare cases, serious kidney damage as a result of exposure to tenofovir.
Researchers in Spain and Italy have been investigating the potential for tenofovir to cause kidney dysfunction. They think that there might be some people who are predisposed to developing tenofovir toxicity. This predisposition appears to occur because in some people there are not sufficient transporter proteins to remove tenofovir and flush it into urine. Tenofovir levels in these people can therefore build up in the blood and kidneys, causing side effects.
Researchers recruited 284 HIV-positive people and divided them into the following three groups:
- regimens containing tenofovir - 154 people
- regimens without tenofovir - 49 people
- not taking treatment - 81 people
Participants had their urine collected over 24 hours and this was used for a toxicity analysis called kidney tubular dysfunction (KTD). Urine samples were checked for abnormal levels of the following substances:
- uric acid
- beta 2 -microglobulin
Having two or more of these substances in the abnormal range resulted in a diagnosis of KTD in this study.
The proportion of people diagnosed with KTD was as follows:
- regimens containing tenofovir - 22%
- regimens without tenofovir - 6%
- not taking treatment - 12%
This difference among tenofovir users and other participants was statistically significant; that is, not likely due to chance alone.
That HIV-positive people not on treatment had a relatively high rate of KTD should not be surprising, as HIV attacks the kidneys and inflames these organs.
The research team then performed a second study with 92 tenofovir users divided into the following groups:
- 18 participants with KTD
- 74 participants without KTD
Blood was drawn from these subjects for analysis between 10 and 14 hours after they had taken tenofovir.
The researchers found that tenofovir levels in the blood of people with KTD were high (about 183 ng/ml) compared to people who were taking tenofovir but who did not have KTD (106 ng/ml). This difference was statistically significant.
Taking into account many factors, the researchers focused on this finding:
- Having a concentration of tenofovir in the blood greater than 160 ng/ml was associated with a 500% increased relative risk for developing KTD.
Additionally, the researchers found that women were more likely to have higher levels of tenofovir in the blood.
Precisely how tenofovir might damage the kidneys of some people is unclear. The Spanish-Italian team speculates that higher-than-normal levels of tenofovir in the blood leads to the accumulation of this drug in the kidney, specifically in the tubes (called tubules) that help filter blood and reabsorb nutrients and other substances.
The study team suggests that tenofovir toxicity is influenced by other factors, such as age and weight.
The Spanish-Italian study has a cross-sectional design-blood was drawn only at one time. This type of study can find associations but cannot prove that tenofovir caused the observed kidney dysfunction. Cross-sectional studies are generally cheaper and faster to do than studies of a more robust design. Indeed, the study team acknowledges that its findings require confirmation in a larger study that monitors people over time.
In summary, the results from the Spanish-Italian study suggest that higher-than-normal levels of tenofovir in the blood are associated with kidney toxicity, detected as kidney tubular dysfunction (KTD).
The researchers warn that prolonged kidney damage arising from tenofovir may result in premature thinning of the bones. So they call for further research to understand the role of tenofovir levels in the blood to prevent and detect tubular damage.
- Sean R. Hosein
Rodríguez-Nóvoa S, Labarga P, D'avolio A, et al. Impairment in kidney tubular function in patients receiving tenofovir is associated with higher tenofovir plasma concentrations. AIDS . 2010 Apr 24;24(7):1064-6.
CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.
From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca
Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE