An Integrated View of Potassium Homeostasis

Gumz, Michelle L.; Rabinowitz, L.; Wingo, Charles S.

doi:10.1056/nejmra1313341

Cited by 242 publications

(215 citation statements)

References 88 publications

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“…Although K + excretion is determined by many factors, 28 these results argue that aldosterone plays an essential and nonredundant role in daily K + balance. We did not perform formal balance studies, however, so that MR effects on plasma [K + ] may not reflect changes in total body K + content as suggested.…”

Section: Discussionmentioning

confidence: 96%

Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport

Terker

Yarbrough

Ferdaus

et al. 2015

JASN

121

113

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Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide-sensitive Na + -Cl 2 cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney-specific MR-knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.

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Section: Discussionmentioning

confidence: 96%

Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport

Terker

Yarbrough

Ferdaus

et al. 2015

JASN

121

113

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“…The plasma potassium level is maintained within rather narrow limits (between 3.6 and 5 mmol/l) and is tightly controlled by multiple mechanisms (6,7). The kidneys are central in controlling systemic potassium homeostasis, as they eliminate more than 90% of a highly variable dietary potassium intake.…”

Section: Introductionmentioning

confidence: 99%

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

Palygin¹,

Levchenko²,

Ilatovskaya³

et al. 2017

JCI Insight

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“…[1] Potassium is regulated by two concurrent processes, an internal system that maintains the total body potassium between intracellular and extracellular fluid and an external system that controls balance and distribution via dietary intake and renal excretion ( Figure 1). …”

Section: Introductionmentioning

confidence: 99%

“…Coupled with passive potassium efflux, the level of intracellular versus extracellular potassium may be shifted by external factors, including certain medications and level of physical activity. [1] External potassium homeostasis relies on healthy renal function for potassium excretion, which occurs in response to increases in serum potassium levels via physiological feedback systems within the body. This type of potassium homeostasis can be compromised by impaired renal excretion as a consequence of a patient's physical condition (i.e., chronic kidney disease [CKD]) or through use of certain medications, such as renin-angiotensin-aldosterone system inhibitors (RAASi).…”

Section: Introductionmentioning

confidence: 99%

“…This type of potassium homeostasis can be compromised by impaired renal excretion as a consequence of a patient's physical condition (i.e., chronic kidney disease [CKD]) or through use of certain medications, such as renin-angiotensin-aldosterone system inhibitors (RAASi). [1] In individuals with unregulated potassium, high levels of serum potassium (≥5.1 mEq/L), or hyperkalemia, is associated with increased rate of death, progression of cardiac and kidney disease, and interstitial fibrosis; and when severe can directly result in fatal cardiac arrhythmias. [1] Hyperkalemia is a common electrolyte disorder in patients with heart failure (HF), CKD, and diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacodynamics and pharmacokinetics of sodium zirconium cyclosilicate [ZS-9] in the treatment of hyperkalemia

Packham

Kosiborod

2016

Expert Opinion on Drug Metabolism & Toxicology

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ZS-9 has a unique mechanism of action consisting of thermodynamically favorable sequestration of potassium ions, enabling rapid trapping and removal of excess potassium. The potassium lowering action of ZS-9 is predictable and rapid, leading to significant reduction of serum potassium within 1 hour of administration by irreversibly eliminating excess potassium rather than acting via intracellular translocation. Its safety profile, including gastrointestinal events, has been generally similar to that of placebo, with the exception of infrequent but manageable events of peripheral edema and transient hypokalemia. ZS-9 has demonstrated potential for enabling renin-angiotensin-aldosterone system inhibitors in mid-term studies, with long-term studies ongoing.

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An Integrated View of Potassium Homeostasis

Cited by 242 publications

References 88 publications

Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport

Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

Pharmacodynamics and pharmacokinetics of sodium zirconium cyclosilicate [ZS-9] in the treatment of hyperkalemia

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