Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1 beta Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension

Background and Objectives: Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1 beta activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1 alpha gene expression from whole blood and urine samples and IL-1 beta gene expression from whole blood were measured. Methods: One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1 alpha and IL-1 beta geneexpression by using quantitative real-time PCR. Results: There were significant differences in whole blood HIF-1 alpha, IL-1 beta geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1 alpha gene expression, IL-1 beta geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1 beta geneexpression were increased in ADPKD patients with high levels of HIF-1 alpha geneexpression (p = 0.018 and p = 0.029, respectively). Conclusions: Increased age,low eGFR, and HIF-1 alpha and IL-1 beta geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD