Association of soluble TNFR-1 concentrations with long-term decline in kidney function: The multi-ethnic study of atherosclerosis

Abstract

Background TNF receptor-1 (TNFR-1), which plays a causative role in endothelial cell dysfunction and inflammation, is expressed on the cell surface in glomerular and peritubular capillary endothelium of the kidneys. Higher soluble TNFreceptor-1 (sTNFR-1) concentrations are associated with kidney disease progression among persons with established diabetic kidney disease. However, no studies have assessed sTNFR-1's role in longterm kidney function changes in a multiethnic population without cardiovascular disease at baseline. Methods We tested associations between baseline sTNFR-1 concentrations and 10-year decline in eGFR (incident ≥40% decline and annual proportional decline) among 2548 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study. Serum creatinine concentrations were determined at enrollment and study years 3, 5, and 10. Results Mean age of participants was 61 years old, 53% were women, and mean baseline eGFR was 79 ml/min per 1.73 m2. Serum sTNFR-1 was inversely associated with baseline eGFR. Over median follow-up of 9.3 years, 110 participants developed ≥40% decline in eGFR; each SD higher concentration of sTNFR1 was associated with higher risk of 40% eGFR decline (adjusted hazard ratio, 1.43; 95% confidence interval [95%CI], 1.16 to 1.77; P,0.001). The highest sTNFR-1 tertile was associated with adjusted annualized decline in eGFR of 1.94% (95% CI, 1.79 to 2.09). Associations persisted across subgroups defined by demographics, hypertension, diabetes, and baseline CKD status. Conclusions Elevated serum sTNFR-1 concentrations are associated with faster declines in eGFR over the course of adecade in a multiethnic population, independent of previously known risk factors for kidney disease progression.