Serum Biomarkers of Macrophage Activation and Incident CKD in People with and without HIV: Findings from the MACS-WIHS Combined Cohort Study

Abstract Background Macrophages play an important role in kidney inflammation and fibrosis. Circulating biomarkers of macrophage activation are elevated in people with HIV (PWH). We therefore determined their associations with kidney function and chronic kidney disease (CKD) risk in people with and without HIV. Methods We analyzed data from two prospective cohorts: the Women’s Interagency HIV Study and Multicenter AIDS Cohort Study. Serum concentrations of soluble (s)CD14, sCD163, galectin-3 (Gal-3) and Gal-3 binding protein (Gal-3BP) were measured between 2004 and 2006. We examined each biomarker’s association with estimated glomerular filtration rate (eGFR) using multivariable linear regression and with incident CKD (two consecutive eGFR <60 mL/min/1.73m2) using cause-specific Cox proportional hazards models, adjusting for socio-demographics, CKD risk factors, and HIV-related factors. Results Among 1,284 participants, 61% were women, 70% were PWH, of whom 59% were virally suppressed (HIV RNA<200 copies/mL); median eGFR was 93 mL/min/1.73m2 at baseline. All macrophage biomarker concentrations were higher in PWH versus without HIV (p<0.05). Cross-sectionally, higher concentrations of sCD14 and Gal-3 were independently associated with lower eGFR (p<0.001). Over a median follow-up of 14.2 years, incident CKD occurred in 23% of PWH and in 11% without HIV. Each standard deviation higher concentration of sCD14 and Gal-3BP was independently associated with 22% and 29% increased CKD risk, respectively. Associations for sCD163 and Gal-3 were attenuated after multivariable adjustment. Findings were similar in analyses restricted to PWH. Conclusion Macrophage activation may mark and/or contribute to CKD development. Studies are needed to determine whether targeting immune activation improves kidney health in PWH.