Systemic succinate, Hypoxia-Inducible factor-1 alpha, and IL-1 beta gene expression in autosomal dominant polycystic kidney disease with and without Hypertension

Kocyigit, Ismail, Taheri, Serpil, Eroglu, Eray, Sener, Elif Funda, Zararsiz, Gokmen, Uzun, Ilknur, Tufan, Esra, Mehmetbeyoglu, Ecmel ORCID: https://orcid.org/0000-0002-4597-6811, Bayramov, Kezban Korkmaz, Sipahioglu, Murat Hayri, Ozkul, Yusuf, Tokgoz, Bulent, Oymak, Oktay and Axelsson, Jonas 2019. Systemic succinate, Hypoxia-Inducible factor-1 alpha, and IL-1 beta gene expression in autosomal dominant polycystic kidney disease with and without Hypertension. Cardiorenal Medicine 9 (6) , pp. 370-381. 10.1159/000500478

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
ISSN:	1664-5502
Date of First Compliant Deposit:	17 January 2023
Date of Acceptance:	9 April 2019
Last Modified:	19 May 2023 00:48
URI:	https://orca.cardiff.ac.uk/id/eprint/154369

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