The epidemiology of glomerular hyperfiltration among men with HIV in the era of highly active antiretroviral therapy
Ng, Derek K.
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Background Men infected with HIV and receiving highly active antiretroviral therapy are at higher risk of metabolic and cardiovascular abnormalities as well as accelerated renal function decline and chronic kidney disease (CKD). Glomerular hyperfiltration, defined as elevated glomerular filtration rate (GFR) to pathologically high levels, is associated with diabetes and hypertension and is a treatable risk factor for CKD. The epidemiology of hyperfiltration has not been described in an HIV population. The purposes of this dissertation is to a) describe the prevalence of elevated GFR using directly measured iohexol GFR, a gold standard; b) describe the incidence of hyperfiltration using the serum creatinine-based CKD-EPI estimated GFR equation, a clinical standard; and c) investigate the effect of hyperfiltration on accelerated GFR decline in the Multicenter AIDS Cohort Study. Methods Data consisted of a nested cross-sectional study within the MACS comprising 241 HIV-uninfected and 367 HIV-infected men with iohexol GFR, and all MACS data in the era of HAART comprising approximately 1373 HIV-uninfected and 1255 HIV-infected men. Hyperfiltration was classified using adapted definitions, including estimating the 90th percentiles among HIV-uninfected men. Competing risks analyses, with age (after 30 years) as the time scale, were used to assess the effect of HIV-infection on incident hyperfiltration. To determine the effect of hyperfiltration on GFR decline, downward inflection points were identified. Results There was a higher prevalence of elevated GFR among HIV-infected men compared to HIV-uninfected men (25% vs. 17%; adjusted odds ratio: 1.70, 95%CI: 1.11, 2.61) based on directly measured GFR. Using estimated CKD-EPI GFR, HIV infection was associated with increased risk of incident hyperfiltration among non-blacks at younger ages that diminished over time. A higher non-significant risk was observed among blacks. Hyperfiltration was not associated with accelerated 5-year GFR decline. Compared to uninfected men, men treated for HIV-infection had a faster 5-year GFR decline. Conclusions Treated HIV infection was associated with an increased independent risk of prevalent and incident hyperfiltration, and varied by race. HIV infection, but not hyperfiltration, was associated with accelerated short term GFR decline. Therapies for metabolic, cardiovascular and renal abnormalities, including hyperfiltration, remain important considerations for HIV management.