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Increased colonic K⁺ excretion through inhibition of the H,K-ATPase type 2 helps reduce plasma K⁺ level in a murine model of nephronic reduction.

ABSTRACT: Hyperkalemia is frequently observed in patients at the end-stage of chronic kidney disease (CKD), and has possible harmful consequences on cardiac function. Many strategies are currently used to manage hyperkalemia, one consisting of increasing fecal K⁺ excretion through the administration of cation-exchange resins. In this study, we explored another more specific method of increasing intestinal K⁺ secretion by inhibiting the H,K-ATPase type 2 (HKA2), which is the main colonic K⁺ reabsorptive pathway. We hypothetised that the absence of this pump could impede the increase of plasma K⁺ levels following nephronic reduction (N5/6) by favoring fecal K⁺ secretion. In N5/6 WT and HKA2KO mice under normal K⁺ intake, the plasma K⁺ level remained within the normal range, however, a load of K⁺ induced strong hyperkalemia in N5/6 WT mice (9.1?±?0.5 mM), which was significantly less pronounced in N5/6 HKA2KO mice (7.9?±?0.4 mM, p?+ in their feces. The absence of HKA2 also increased fecal Na⁺ excretion by inhibiting its colonic ENaC-dependent absorption. We also showed that angiotensin-converting-enzyme inhibitor like enalapril, used to treat hypertension during CKD, induced a less severe hyperkalemia in N5/6 HKA2KO than in N5/6 WT mice. This study therefore provides the proof of concept that the targeted inhibition of HKA2 could be a specific therapeutic maneuver to reduce plasma K⁺ levels in CKD patients.

SUBMITTER: Walter C

PROVIDER: S-EPMC7815745 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Increased colonic K+ excretion through inhibition of the H,K-ATPase type 2 helps reduce plasma K+ level in a murine model of nephronic reduction.

Walter Christine C Rafael Chloé C Genna Anthony A Baron Stéphanie S Crambert Gilles G

Scientific reports 20210119 1

Hyperkalemia is frequently observed in patients at the end-stage of chronic kidney disease (CKD), and has possible harmful consequences on cardiac function. Many strategies are currently used to manage hyperkalemia, one consisting of increasing fecal K+ excretion through the administration of cation-exchange resins. In this study, we explored another more specific method of increasing intestinal K+ secretion by inhibiting the H,K-ATPase type 2 (HKA2), which is the main colo ...[more]

PMID: 33469051

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Dataset Information

Increased colonic K⁺ excretion through inhibition of the H,K-ATPase type 2 helps reduce plasma K⁺ level in a murine model of nephronic reduction.

Publications

Increased colonic K<sup>+</sup> excretion through inhibition of the H,K-ATPase type 2 helps reduce plasma K<sup>+</sup> level in a murine model of nephronic reduction.

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