Plasma levels of endothelin-1 and renal function among young and healthy adults

Endothelin-1 (ET-1), a vasoconstrictive and pro-inflammatory peptide, is associated with several cardiovascular risk factors and outcomes. We aimed to investigate the association of plasma ET-1 levels and renal function among young and healthy adults.

Individuals aged 25-41 years were enrolled in a population-based cohort study. Main exclusion criteria were established kidney disease, cardiovascular diseases, diabetes mellitus and a body mass index>35 kg/m2. Fasting venous plasma samples were used to measure creatinine, cystatin C and ET-1. The estimated glomerular filtration rate (eGFR) was calculated using the creatinine based chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Multivariable regression models were constructed to assess interrelationships of plasma ET-1 with parameters of renal function.

Median age of the 2139 participants was 37 years, 47% males. Median creatinine and eGFR were 67 μmol/L and 112 mL/min/1.73 m2, respectively. Using quartile one as the reference group, the β-coefficients (95% confidence intervals [CIs]) for eGFR were 0.06 (- 1.22 to 1.35),-0.66 (- 1.95 to 0.62) and-1.70 (- 3.01 to-0.39) for quartiles 2-4 (p-for-trend=0.0056), respectively and β-coefficients (95% CIs) for cystatin C were 0.002 (- 0.01 to 0.02), 0.02 (0.003-0.03) and 0.03 (0.01-0.04) for quartiles 2-4 (p-for-trend<0.0001), respectively. Using ET-1 as a continuous variable, the β-coefficient (95% CI) for eGFR per 1-unit increase was-1.82 (- 3.19 to-0.44, p=0.0095) and 0.02 (0.01-0.04, p=0.0003) for cystatin C. Similar results were found between creatinine and ET-1 levels.

ET-1 levels are strongly associated with parameters of renal function among young and healthy adults, suggesting an important role of ET-1 and endothelial function in the regulation of kidney function.