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

Kocyigit İ., Taheri S., Eroglu E., Sener E. F., Zararsız G., Uzun I., ...Daha Fazla

CARDIORENAL MEDICINE, cilt.9, sa.6, ss.370-381, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 9 Sayı: 6
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1159/000500478
  • Dergi Adı: CARDIORENAL MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.370-381
  • Anahtar Kelimeler: Hypoxia-inducible factor-1 alpha, Hypertension, Polycystic kidney disease, Succinate, TOLL-LIKE RECEPTORS, ENDOTHELIAL DYSFUNCTION, INFLAMMATION, HIF-1-ALPHA, PROGRESSION, DIAGNOSIS, INNATE
  • Erciyes Üniversitesi Adresli: Evet

Özet

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.