Downregulation of the Cl-/HCO3-Exchanger Pendrin in Kidneys of Mice with Cystic Fibrosis: Role in the Pathogenesis of Metabolic Alkalosis

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Mujan Varasteh KiaManoocher Soleimani

Abstract

Patients with cystic fibrosis (CF) are prone to the development of metabolic alkalosis; however, the pathogenesis of this life threatening derangement remains unknown. We hypothesized that altered acid base transport machinery in the kidney collecting duct underlies the mechanism of impaired bicarbonate elimination in the CF kidney. Balance studies in metabolic cages were performed in WT and CFTR knockout (CF) mice with the intestinal rescue in response to bicarbonate loading or salt restriction, and the expression levels and cellular distribution of acid base and electrolyte transporters in the proximal tubule, collecting duct and small intestine were examined by western blots, northern blots and/or immunofluorescence labeling. Baseline parameters, including acid-base and systemic vascular volume status were comparable in WT and CF mice, as determined by blood gas, kidney renin expression and urine chloride excretion. Compared with WT animals, CF mice demonstrated a significantly higher serum HCO3- concentration (22.63 in WT vs. 26.83 mEq/l in CF mice; n=4, p=0.013) and serum pH (7.33 in WT vs. 7.42 in CF mice; n=4, p=0.00792) and exhibited impaired kidney HCO3- excretion (urine pH 8.10 in WT vs. 7.35 in CF mice; n=7, p=0.0099...Continue Reading

Citations

Jan 25, 2019·Physiological Reports·John J BisslerManoocher Soleimani
Jun 2, 2020·Annals of Internal Medicine·Sudip GhimireMartin Sedlacek
Jul 25, 2020·Journal of the American Society of Nephrology : JASN·Peder BergJens Leipziger
Apr 26, 2020·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Thi Nga NguyenHideaki Suzuki
Oct 12, 2020·Biochemical Pharmacology·Bianca N QuadeRossana Occhipinti
Jul 19, 2020·Journal of the Academy of Nutrition and Dietetics·Dimitri DeclercqStephanie Van Biervliet
May 25, 2021·Current Opinion in Nephrology and Hypertension·Peder BergJens Leipziger
May 9, 2021·The Journal of Physiology·Peder BergJens Leipziger

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