Association of the serum endostatin level, renal function, and carotid atherosclerosis of healthy residents of Japan: Results from the kyushu and okinawa population study (KOPS)

Aim: To analyze associations among the serum endostatin level, renal function, and carotid atherosclerosis of healthy residents of Japan. Methods: Among 1,057 Japanese residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents (200 men and 448 women, age 24 to 84 years) for whom the serum endostatin level and common carotid intima-media thickness (IMT) were measured. Renal function was assessed by estimated glomerular filtration rate (eGFR). Multiple linear regression analysis was done to determine the association of eGFR and serum endostatin level after adjustment for known covariates. Mediation analysis was done using Baron and Kenny’s regression approach. Results: The median endostatin level was 63.7 ng/mL (interquartile range: 49.7–93.2). The mean eGFR was 78.4±14.8 mL/min/1.73m². Univariate analysis showed that age (r =－0.37, P＜0.01), non current smoking (85.8±13.0 vs. 77.5±14.8 mL/min/1.73 m², P＜0.01), hemoglobin A1c (r=－0.08, P=0.05), low-density lipo-protein-cholesterol (r =－0.13, P＜0.01), uric acid (r =－0.15, P＜0.01), carotid IMT (r=－0.11, P＜0.01), and log-transformed endostatin (r=－0.36, P＜0.01) were significantly associated with eGFR. In multiple linear regression analysis, log-transformed endostatin was significantly associated with eGFR (beta=－0.24, P＜0.01). While, carotid IMT was no longer significant. Mediation analysis showed serum endostatin level to be a mediator in the association between carotid IMT and eGFR. Conclusions: The association between carotid IMT and eGFR is mediated by the serum endostatin level of healthy individuals.