Open AccessSystemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension
Author(s) -
İsmail Koçyiğit,
Serpil Taheri,
Eray Eroğlu,
Elif Funda Şener,
Gökmen Zararsız,
İlknur Uzun,
Esra Tufan,
Ecmel Mehmetbeyoğlu,
Keziban Korkmaz Bayramov,
Murat Hayri Sipahioğlu,
Yusuf Özkul,
Bülent Tokgöz,
Oktay Oymak,
Jonas Axelsson
Publication year - 2019
Publication title -
cardiorenal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.661
H-Index - 21
eISSN - 1664-3828
pISSN - 1664-5502
DOI - 10.1159/000500478
Subject(s) - autosomal dominant polycystic kidney disease , medicine , endocrinology , hypoxia (environmental) , blood pressure , kidney , whole blood , aldosterone , hypoxia inducible factors , renin–angiotensin system , kidney disease , polycystic kidney disease , biology , gene , chemistry , biochemistry , organic chemistry , oxygen
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-1β 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-1α gene expression from whole blood and urine samples and IL-1βgene 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-1α and IL-1β geneexpression by using quantitative real-time PCR. Results: There were significant differences in whole blood HIF-1α, IL-1β geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1β 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-1β geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively). Conclusions: Increased age,low eGFR, and HIF-1α and IL-1β 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.