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Review
. 2020 Sep 2;13(6):952-968.
doi: 10.1093/ckj/sfaa157. eCollection 2020 Dec.

Dietary potassium and the kidney: lifesaving physiology

Kuang-Yu Wei  1   2 , Martin Gritter  1 , Liffert Vogt  3 , Martin H de Borst  4 , Joris I Rotmans  5 , Ewout J Hoorn  1
Affiliations
Review

Dietary potassium and the kidney: lifesaving physiology

Kuang-Yu Wei et al. Clin Kidney J. .

Abstract

Potassium often has a negative connotation in Nephrology as patients with chronic kidney disease (CKD) are prone to develop hyperkalaemia. Approaches to the management of chronic hyperkalaemia include a low potassium diet or potassium binders. Yet, emerging data indicate that dietary potassium may be beneficial for patients with CKD. Epidemiological studies have shown that a higher urinary potassium excretion (as proxy for higher dietary potassium intake) is associated with lower blood pressure (BP) and lower cardiovascular risk, as well as better kidney outcomes. Considering that the composition of our current diet is characterized by a high sodium and low potassium content, increasing dietary potassium may be equally important as reducing sodium. Recent studies have revealed that dietary potassium modulates the activity of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule (DCT). The DCT acts as a potassium sensor to control the delivery of sodium to the collecting duct, the potassium-secreting portion of the kidney. Physiologically, this allows immediate kaliuresis after a potassium load, and conservation of potassium during potassium deficiency. Clinically, it provides a novel explanation for the inverse relationship between dietary potassium and BP. Moreover, increasing dietary potassium intake can exert BP-independent effects on the kidney by relieving the deleterious effects of a low potassium diet (inflammation, oxidative stress and fibrosis). The aim of this comprehensive review is to link physiology with clinical medicine by proposing that the same mechanisms that allow us to excrete an acute potassium load also protect us from hypertension, cardiovascular disease and CKD.

Keywords: CKD; albuminuria; aldosterone; blood pressure; hyperkalaemia; hypertension; nutrition.

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Figures

FIGURE 1
FIGURE 1
Overview of the main apical transport pathways contributing to Na+ reabsorption and K+ secretion in the ASDN. In the initial two-thirds of the DCT (DCT1), the apical NCC is the major Na+ transporter, which mediates electroneutral Na+ reabsorption. In the final one-third of the DCT (DCT2), NCC is co-expressed with the ENaC and ROMK. K+ secretion progressively increases in the principal cells of DCT2, CNT and CCD that express ENaC and ROMK. Na+ reabsorption by ENaC is electrogenic and is regulated by aldosterone. Na+ reabsorption through ENaC generates a lumen-negative transepithelial voltage that drives K+ secretion via ROMK. BK channels mediate flow-dependent K+ secretion in the collecting duct. The three major factors that promote K+ secretion are (i) Na+ delivery to CNT/CCD, (ii) tubular flow rate and (iii) aldosterone.
FIGURE 2
FIGURE 2
Model of how the DCT and ASDN work in concert in response to a low or high K+ diet. (A) A low K+ diet leads to phosphorylation (activation) of the NCC in the DCT, resulting in increased electroneutral Na+ reabsorption through NCC. This will reduce Na+ delivery to the ASDN and inhibit electrogenic Na+ reabsorption through the ENaC and K+ secretion through ROMK. (B) A high K+ diet leads to dephosphorylation (inactivation) of NCC, thereby reducing electroneutral Na+ reabsorption. This increases Na+ delivery to the ASDN for electrogenic Na+ reabsorption through ENaC and drives K+ secretion through ROMK.
FIGURE 3
FIGURE 3
Molecular pathways involved in the effects of a low K+ diet on the NCC. A low extracellular K+ concentration is sensed by the K+ channel Kir 4.1/5.1, resulting in efflux of K+ through Kir4.1/5.1. This leads to membrane hyperpolarization and chloride (Cl−) efflux through a basolateral voltage-gated Cl−channel (ClC-Kb/barttin). A reduction in intracellular Cl− concentration relieves the inhibition of WNK4 autophosphorylation. In turn, phosphorylated WNK4 activates SPAK–OSR1, which phosphorylates NCC. In Drosophila melanogaster kidney tubules, WNK4 phosphorylation of SPAK–OSR1 depends on the scaffold protein Mo25.
FIGURE 4
FIGURE 4
Molecular pathways involved in the effects of a high K+ diet on the NCC. High extracellular K+ concentration is sensed by K+ channel Kir4.1/5.1 and causes membrane depolarization. This may lead to an increase in intracellular calcium (Ca2+) through unknown mechanisms. Ca2+ stimulates calcium-binding protein calmodulin (CaM) and downstream PPs such as PP3 (calcineurin). This dephosphorylates NCC. In acute K+ loading, mechanisms that depend on intracellular chloride ([Cl−]in) may also be stimulated through effects dependent on the K+ channel Kir4.1/5.1. An increase in [Cl−]in may inhibit WNK4 autophosphorylation. This would prevent SPAK–OSR1 phosphorylation and ultimately, NCC phosphorylation.
FIGURE 5
FIGURE 5
Working hypothesis of how dietary K+ may confer cardiovascular and kidney protection. The effects of dietary K+ may either be relayed through its effect on the microbiome and its metabolites (gut–vessel and gut–kidney signalling) or through plasma K+. The protective effects of K+ can be mediated both through BP-dependent and -independent mechanisms.
FIGURE 6
FIGURE 6
Overview of cohort studies that analysed the association between urinary K+ or urine Na+/K+ (as proxy for dietary intake) and kidney outcomes. The average baseline eGFR is shown for each cohort.
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