Circulating endothelin-1 levels are positively associated with chronic kidney disease in women but not in men: a longitudinal study in the Vara-Skövde cohort

Background: The vasoconstricting peptide endothelin-1 (ET-1) is associated with endothelial dysfunction. The aim of this paper was to investigate whether circulating ET-1 levels predicts chronic kidney disease (CKD) in a prospective population study. Methods: In 2002-2005, 2816 participants (30-74 years) were randomly selected from two municipalities in South-Western Sweden and followed up in a representative sample of 1327 individuals after ten years. Endothelin-1 levels were assessed at baseline. Outcome was defined as CKD stage 3 or above based on eGFR < 60 mL/min/1.73m 2 . Those 1314 participants with successful analysis of ET-1 were further analyzed using binary logistic regression. Results: At follow-up, 47 (7.2%) men and 63 (9.6%) women had CKD stage 3 and above. The level of ET-1 was divided into quintiles showing that women in the highest quintile (n=132) had a significantly increased risk of developing CKD during the follow up period (OR=2.379, 95% CI:1.23-4.61, p<0.01) compared with the other quintiles (1-4), even when adjusted for age, physical activity, current smoking, alcohol consumption, hypertension, diabetes, BMI, high- sensitive CRP and LDL-cholesterol (OR=2.66, 95% CI:1.29-5.49, p<0.01). No significant differences were observed between quintiles of ET-1 and development of CKD in men (NS). Conclusions: High levels of ET-1 are associated with development of CKD in women but not in men.