Potassium and Its Discontents

Abstract

Hyperkalemia is common in patients with impaired kidney function or who take drugs that inhibit the renin-angiotensin-aldosterone axis. During the past decade, substantial advances in understanding how the body controls potassium excretion have been made, which may lead to improved standard of care for these patients. Renal potassium disposition is primarily handled by a short segment of the nephron, comprising part of the distal convoluted tubule and the connecting tubule, and regulation results from the interplay between aldosterone and plasma potassium. When dietary potassium intake and plasma potassium are low, the electroneutral sodium chloride cotransporter is activated, leading to salt retention. This effect limits sodium delivery to potassium secretory segments, limiting potassium losses. In contrast, when dietary potassium intake is high, aldosterone is stimulated. Simultaneously, potassium inhibits the sodium chloride cotransporter. Because more sodium is then delivered to potassium secretory segments, primed by aldosterone, kaliuresis results. When these processes are disrupted, hyperkalemia results. Recently, new agents capable of removing potassium from the body and treating hyperkalemia have been tested in clinical trials. This development suggests that more effective and safer approaches to the prevention and treatment of hyperkalemia may be on the horizon.

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

“…The beneficial effects of dietary potassium are most likely related to the reduced activity of NKCC2 and NCC. It was recently reported that NCC activity in the DCT is induced by augmented plasma K + (41,50). The rapid phosphorylation of NCC in response to a low-potassium diet involves activation of WNK/SPAK by decreased intracellular Cl -concentrations due to hyperpolarization of the cell membrane in the DCT cells (8,51).…”

“…Dietary potassium loading results in rapid kaliuresis, diuresis, and natriuresis (7,40,41), and the next aim was to test the effect of high-K + supplementation in SS Kcnj16-/-rats on body and kidney weights. As summarized in Figure 9, the kidney and body weights of SS Kcnj16-/-rats were significantly improved when the dietary potassium content was increased.…”

Mutant Cullin 3 causes familial hyperkalemic hypertension via dominant effects

“…Increased NCC activity causes excessive Na + reabsorption that raises extracellular fluid volume and, thus, blood pressure. It has also been proposed to cause hyperkalemia by reducing Na + delivery to the epithelial sodium channel (ENaC) along the collecting duct (CD), which decreases the electrogenic drive for K + secretion through the renal outer medullary K + channel (ROMK) (11)(12)(13)(14)(15). However, it should be noted that direct effects of Wnk mutations on Na + -K + -2Cl -cotransporter (NKCC2) (16), ENaC (16,17), …”

Role and mechanisms of regulation of the basolateral Kir4.1/Kir5.1K+channels in the distal tubules

“…As it was recently summarized by Ellison et al ., there is direct link between the dietary K + intake and activity of NCC cotransporter in DCT (Ellison et al . ). Sorensen et al .…”