Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.

Abstract

Autosomal-dominant polycystic kidney disease (ADPKD) is associated with oxidative stress and hypertension development before renal function decline and cardiovascular disease development. Oxidative stress-responsive kinase-1 (OSR-1) participates in the signaling regulating Na+ transport during oxidative stress and also plays a role in the regulation of cell volume and blood pressure. Therefore, we aimed to investigate the potential role of OSR-1 in ADPKD patients. Eighty ADPKD patients, 80 healthy controls, and 80 non-ADPKD patients with hypertension were enrolled in this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood samples were taken after 12-h fasting for the measurement of biochemical parameters and OSR-1 gene expression. Vascular dysfunction was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Briefly, of the 80 ADPKD patients, 41(51%) were male, and 53(66%) of them were hypertensive. The mean age of the 80 controls was 35.3 ± 12.6 years, and 37(46%) of them were male. The mean age of the 80 non-ADPKD patients with hypertension was 44.6 ± 11.9 years, and 38(47.5) of them were male. There were significant differences in serum OSR-1 gene expression between the ADPKD patients and the control subjects. Serum OSR-1 gene expression was also significantly increased in hypertensive ADPKD patients in comparison with both normotensive ADPKD counterparts and non-ADPKD hypertensive subjects. Serum OSR-1 gene expression was increased in patients with ADPKD than healthy subjects. Low estimated glomerular filtration rate (eGFR), OSR-1 gene expression, total kidney volume (TKV), and high-density lipoprotein (HDL) were also independently associated with hypertension in ADPKD patients.