Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency

Todkar A, Picard N, Loffing-Cueni D, Sorensen MV, Mihailova M, Nesterov V, Makhanova N, Korbmacher C, Wagner CA, Laffing J (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Journal of the American Society of Nephrology American Society of Nephrology

Book Volume: 26

Pages Range: 425-38

Journal Issue: 2

DOI: 10.1681/ASN.2013111156

Abstract

Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High-K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(-/-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K(+) excretion was detected only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was downregulated in mice of both genotypes in response to increased K(+) intake. Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-) mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can be achieved in aldosterone deficiency by aldosterone-independent activation of the renal outer medullary K(+) channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K(+) secretion and increased intratubular availability of Na(+) that can be reabsorbed in exchange for K(+) secreted.

Authors with CRIS profile

Viatcheslav Nesterov Lehrstuhl für Physiologie (Vegetative Physiologie) Christoph Korbmacher Lehrstuhl für Physiologie (Vegetative Physiologie)

Involved external institutions

University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) University of North Carolina at Chapel Hill US United States (USA) (US)

How to cite

APA:

Todkar, A., Picard, N., Loffing-Cueni, D., Sorensen, M.V., Mihailova, M., Nesterov, V.,... Laffing, J. (2015). Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency. Journal of the American Society of Nephrology, 26(2), 425-38. https://doi.org/10.1681/ASN.2013111156

MLA:

Todkar, Abhijeet, et al. "Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency." Journal of the American Society of Nephrology 26.2 (2015): 425-38.

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