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Older Age Impairs Kidney Function During Tenofovir Therapy
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11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento
Mark Mascolini
Among people taking tenofovir, estimated glomerular filtration rate (eGFR) fell 11 mL/min more for every year of age in 30-to-45-year-olds than in people under 30, according to a 1031-person analysis at Johns Hopkins University in Baltimore [1]. Compared with people younger than 30, people over 45 had a 15 mL/min per year greater drop in eGFR when taking tenofovir. Number of days taking tenofovir and protease inhibitor use also independently lowered eGFR. The analysis is limited, observed Hopkins investigator Keith Crawford, by the relatively short 701-day average tenofovir duration in this cohort.
Aging is a well-recognized correlate of declining kidney function in the general population. And it's no news that the HIV population is aging as improved therapies tighten control of HIV. At the Hopkins clinic, median age of people with HIV stands at 48. In Italy, Giovanni Di Perri told Pharmacology Workshop attendees, the average age at HIV diagnosis has climbed to 43.
Tenofovir slows creatinine clearance and has been linked to renal tubular damage and Fanconi syndrome. To weigh the impact of age on creatinine clearance in people taking tenofovir, the Johns Hopkins team retrospectively tracked eGFR (calculated by MDRD) in all 1031 patients who took tenofovir in their clinic from 2002 to 2009. The analysis rested on 17,383 eGFR observations.
Two thirds of the study group were men, and two thirds were African American. Over the study period, individuals had a median of 10 clinic visits (interquartile range 4 to 16) while taking tenofovir for an average of 701 days. At the initial clinic visits, eGFR averaged 112.7 mL/min. In univariate analysis, average eGFR declined 0.016 mL/min for each day of tenofovir use (P < 0.000). That decline appeared to start flattening out after 300 days of tenofovir use in the three age groups analyzed: under 30, 30 to 45, and over 45.
Crawford and colleagues constructed a multivariate model that factored in HCV infection (affecting 24.6% of this cohort), diabetes (affecting 11.3%), initial MDRD-determined eGFR, PI use, nonnucleoside use, gender, and race. This analysis determined that, compared with the under-30 group, people from 30 to 45 years old saw their eGFR drop 11.07 mL/min more for every year of age (confidence interval [CI] -17.06 to -4.97, P < 0.0001). Compared with the under-30 group, people over 45 had a 15.39-mL/min per year greater decline in eGFR (CI -21.73 to -9.07, P < 0.0001).
The eGFR drop for people taking tenofovir under 300 days was 0.0351 mL/min, compared with 0.016 mL/min for people taking the drug more than 300 days. PI use was associated with a 4.28 mL/min eGFR decline compared with non-PI regimens (CI -7.21 to -1.34, P < 0.004). Baseline MDRD value also independently predicted creatinine clearance, but HCV infection, diabetes, age, and gender did not.
The Hopkins team suggested that the changes in eGFR seen with tenofovir, though statistically significant, may not be clinically relevant on their own. But because tenofovir, PIs, and older age all independently lower eGFR, people with two or three of these risk factors probably deserve special attention.
Reference
1. Goeddel L, Crawford KW, Moore R, Fine DM, Atta M, Flexner C. Impact of age on renal function in patients receiving tenofovir. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 38.
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