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Jasmine Riviere Marcelin from the Mayo Clinic in Rochester and colleagues performed a retrospective chart review looking at frequency of and risk factors associated with kidney dysfunction among people with HIV taking tenofovir (Viread, also in several coformulations including Truvada).

This analysis included 117 HIV positive adults in the Mayo Clinic HIV Database who took tenofovir between 2010 and 2013 and who received at least 1 urinalysis and test for serum creatinine, a marker of kidney function. Most (81%) were men, about 80% were white, 19% were African-American -- a group at greater risk for chronic kidney disease -- and the mean age was 45 years.

Kidney Function Markers

Participants had been taking antiretroviral therapy (ART) containing tenofovir for a median of about 3 years, most had good viral suppression (median 62 copies/mL), and the median CD4 T-cell count was about 450 cells/mm³. Looking at other conditions, 33% had abnormal blood lipids, 24% had hypertension (high blood pressure), 14% had hepatitis C, and 12% had hepatitis B; 21% were taking the antibiotic TMP-SMX, which can also cause kidney toxicity. With regard to kidney function markers at baseline, 68% had an abnormal protein-osmolality (P:O) indicating protein in the urine, 39% had abnormal predicted 24-hour proteinuria, and 9% had abnormal estimated glomerular filtration rate (eGFR).

Results

• After adjusting for age, patients taking tenofovir for more than 5 years had nearly a 4-fold higher risk of having abnormal P:O than people on tenofovir for less than 1 year (odds ratio [OR] 3.9).
• Increasing age was associated with abnormal P:O ratio (OR 1.42), abnormal 24-hour proteinuria (OR 1.5), and a 2-fold higher risk of abnormal eGFR (OR 2.1).
• All 11 diabetic patients had an abnormal P:O ratio.
• Patients with hypertension were nearly 4 times more likely to have abnormal eGFR (OR 3.8).
• However, neither abnormal P:O ratio nor abnormal predicted 24-hour proteinuria were associated with a significantly increased risk of abnormal eGFR.

"Abnormal renal function is common in HIV infected patients on tenofovir but rarely progresses to abnormal eGFR," the researchers summarized. "Duration of tenofovir use, age, diabetes, and hypertension are risk factors for the development of renal dysfunction in these patients," they added. "Therefore, caution should be used when prescribing this medication in older patients or patients with hypertension or diabetes."

As neither abnormal P:O ratio nor predicted 24-hour proteinuria were associated with development of abnormal eGFR, they concluded that serum creatinine remains the "gold standard" for monitoring kidney function while on tenofovir. 

Low Body Weight

In the second study, described in the August 24 edition of AIDS, Takeshi Nishijimafrom the AIDS Clinical Center of the National Center for Global Health and Medicine in Tokyo and colleagues looked at the effect of long-term tenofovir use on kidney function in people with low body weight who may be more vulnerable to nephrotoxicity.

This observational study included 792 treatment-naive people with HIV at a single center in Tokyo. Of these, 422 started ART containing tenofovir while the remaining 370 took regimens containing abacavir (Ziagen, also in Epzicom) and served as a control group. Almost all were men, the mean age was 36 years, and the median CD4 count was approximately 190 cells/mm³. The median body weight was 63 kg (139 lb) and the median body mass index was 22 (18.5-24.9 is considered normal weight).

The researchers estimated the effect of tenofovir use on eGFR over 10 years. The 3 kidney function endpoints were a decrease in eGFR of more than 10 mL/min/1.73 m² relative to baseline, a greater than 25% decrease in eGFR, and eGFR below 60 mL/min/1.73 m² measured at least 3 months apart.

Results

• Patients taking tenofovir had a significantly higher likelihood of all 3 abnormal kidney function outcomes compared with the control group:

o   2-fold higher risk of a 10 mL/min/1.73 m² decrease in eGFR (adjusted OR 2.1);

o   2-fold higher risk of >25% decrease in eGFR (adjusted OR 2.1);

o   4-fold higher risk of eGFR below 60 mL/min/1.73 m² (adjusted OR 3.9).

• eGFR loss increased with greater duration of tenofovir exposure.
• Cumulative mean eGFR loss after 1, 2, 3, 4, and 5 years on tenofovir, relative to the control group, was -3.8, -3.6, -5.5, -6.6, and -10.3 mL/min/1.73 m², respectively.

"In this cohort of patients with low body weight, [tenofovir] exposure increased the risk of renal dysfunction," the study authors concluded. "Furthermore, the loss in eGFR relative to the control [group] increased continuously up to 5 years."

Furthermore, the effect of tenofovir on the decrement in eGFR "was more evident" in patients with body weight of lower than 70 kg (154 lb) compared with the entire study population, they noted in their discussion. The adjusted OR for tenofovir recipients relative to the control group was 2.5 for people weighing less than 70 kg versus 2.1 for the population as a whole. In fact, the effect of tenofovir on kidney function was "only marginally significant" among people weighing at least 70 kg (adjusted OR 1.7).

The decline in eGFR associated with tenofovir use "is alarming considering that the aging-related decrement in normal renal function is only 0.4 mL/min per year," they wrote.

"The results of the study certainly warrant regular and long-term monitoring of renal function in patients with low body weight who start [tenofovir]-containing ART," they advised. "Further larger studies are needed to confirm the long-term renal prognosis with [tenofovir] use in patients with low body weight."

10/17/14

References

J Riviere Marcelin, M Berg, MW Cummins and S Rizza. Risk factors for Tenofovir-associated Renal Dysfunction in HIV-positive Patients. IDWeek 2014. Philadelphia, October 8-12, 2014. Abstract 1571.

T Nishijima, Y Kawasaki, N Tanaka, et al. Long-term Exposure to Tenofovir Continuously Decrease Renal Function in HIV-1-Infected Patients With Low Body Weight. AIDS 28(13):1903-1910. August 24, 2014.