Association between Endothelin-1 Levels and Kidney Disease among Blacks

Endothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000-2004; n=3538). We defined incident CKD as eGFR<60 ml/min per 1.73 m² and ≥30% eGFR decline at the third visit (2009-2013) relative to baseline among those participants with baseline eGFR ≥60 ml/min per 1.73 m² At baseline, mean age was 55 years old, 37% of participants were men, and mean eGFR was 94 ml/min per 1.73 m² Over a median follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants. Participants with baseline endothelin-1 levels in higher quartiles had a greater incidence of CKD in the fully adjusted model (odds ratio for fourth versus first quartile, 1.81; 95% confidence interval, 1.11 to 2.96; P_trend=0.04). Endothelin-1 positively associated with all-cause mortality (hazard ratio for fourth versus first quartile, 1.64; 95% confidence interval, 1.24 to 2.16; P_trend<0.001). In conclusion, higher baseline serum endothelin-1 levels associated with incident CKD and all-cause mortality during follow-up in this general population sample of blacks.