Article ; Online: 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
Scientific Reports, Vol 11, Iss 1, Pp 1-
2021 Volume 10
Abstract: 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 ... ...
| Abstract | 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 < 0.01). This was correlated to a higher capacity of HKA2KO mice to excrete K+ 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. |
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| Keywords | Medicine ; R ; Science ; Q |
| Language | English |
| Publishing date | 2021-01-01T00:00:00Z |
| Publisher | Nature Portfolio |
| Document type | Article ; Online |
| Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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