Effect of increased potassium intake on the renin–angiotensin–aldosterone system and subcutaneous resistance arteries: a randomized crossover study

Dreier, Rasmus; Abdolalizadeh, Bahareh; Asferg, Camilla; Hølmich, Lisbet Rosenkrantz; Buus, Niels Henrik; Forman, Julie Lyng; Andersen, Ulrik B.; Egfjord, Martin; Sheykhzade, Majid; Jeppesen, Jørgen

doi:10.1093/ndt/gfaa292

Cited by 2 publications

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“…Third, the fact that we did not observe a rise in plasma renin suggests that KCl supplementation failed to induce potassium-induced natriuresis. In healthy males, 90 mmol KCl did increase plasma renin and angiotensin II, likely reflecting urinary sodium chloride loss with secondary activation of the renin-angiotensin system 49 . Potassium-induced natriuresis is one of the proposed mechanisms by which potassium reduces BP, an effect that is mediated by potassium’s inhibition of the thiazide-sensitive sodium-chloride cotransporter 31 , 50 – 52 .…”

Section: Discussionmentioning

confidence: 99%

“…In healthy males, 90 mmol KCl did increase plasma renin and angiotensin II, likely reflecting urinary sodium chloride loss with secondary activation of the renin-angiotensin system. 49 Potassium-induced natriuresis is one of the proposed mechanisms by which potassium reduces BP, an effect that is mediated by potassium's inhibition of the thiazide-sensitive sodium-chloride cotransporter. 31,[50][51][52] Finally, the BP-lowering effect of potassium may have been offset by the increase in plasma aldosterone or the development of hyperchloremic metabolic acidosis.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD

Gritter

Wouda

Yeung

et al. 2022

JASN

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BackgroundObservational studies suggest that adequate dietary potassium intake (90–120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the risk of hyperkalemia are unknown.MethodsThis is a prespecified analysis of the run-in phase of a clinical trial in which 191 patients (age 68±11 years, 74% males, 86% European ancestry, eGFR 31±9 ml/min per 1.73 m2, 83% renin-angiotensin system inhibitors, 38% diabetes) were treated with 40 mmol potassium chloride (KCl) per day for 2 weeks.ResultsKCl supplementation significantly increased urinary potassium excretion (72±24 to 107±29 mmol/day), plasma potassium (4.3±0.5 to 4.7±0.6 mmol/L), and plasma aldosterone (281 [198–431] to 351 [241–494] ng/L), but had no significant effect on urinary sodium excretion, plasma renin, BP, eGFR, or albuminuria. Furthermore, KCl supplementation increased plasma chloride (104±3 to 105±4 mmol/L) and reduced plasma bicarbonate (24.5±3.4 to 23.7±3.5 mmol/L) and urine pH (all P<0.001), but did not change urinary ammonium excretion. In total, 21 participants (11%) developed hyperkalemia (plasma potassium 5.9±0.4 mmol/L). They were older and had higher baseline plasma potassium.ConclusionsIn patients with CKD stage G3b–4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium. Longer-term studies should address whether cardiorenal protection outweighs the risk of hyperkalemia.Clinical trial number:NCT03253172

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD

Gritter

Wouda

Yeung

et al. 2022

JASN

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Amiloride lowers plasma TNF and interleukin-6 but not interleukin-17A in patients with hypertension and type 2 diabetes

Thangaraj,

Oxlund,

Andersen

et al. 2024

American Journal of Physiology-Renal Physiology

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Interleukin-17A (IL-17A) contributes to hypertension in preclinical models. Th-17 and dendritic cells are activated by NaCl which could involve the epithelial sodium channel (ENaC). We hypothesized that the ENaC blocker amiloride reduces plasma IL-17A and related cytokines in patients with hypertension. Concentrations of IL-17A, IFN-γ, TNF, IL-6, IL-1β, and IL-10 were determined by immunoassays in plasma from two patient cohorts before and after amiloride treatment: 1) patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension (n=69, amiloride 5-10mg/day for 8weeks); 2) patients with hypertension and T1DM (n=29) on standardized salt intake (amiloride 20-40mg/day, 2 days). Plasma and tissue from ANGII-hypertensive mice with T1DM treated with amiloride (2mg/kg/day, 4 days) were analyzed. The effect of amiloride and benzamil on macrophage cytokines was determined in vitro. Plasma cytokines showed higher concentrations (IL-17A~40-fold) in patients with T2DM compared with T1DM. In patients with T2DM, amiloride had no effect on IL-17A but lowered TNF and IL-6. In patients with T1DM, amiloride had no effect on IL-17A but increased TNF. In both cohorts, blood pressure decline and plasma K+ increase did not relate to plasma cytokine changes. In mice, amiloride exerted no effect on IL-17A in plasma, kidney, aorta, or left cardiac ventricle but increased TNF in cardiac and kidney tissues. In lipopolysaccharide-stimulated human THP-1 macrophages, amiloride and benzamil (from 1 nmol/L) decreased TNF, IL-6, IL-10, and IL-1β. In conclusion, inhibition of ENaC by amiloride reduces proinflammatory cytokines TNF and IL-6, but not IL-17A in vivo, potentially by a direct action on macrophages.

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Effect of increased potassium intake on the renin–angiotensin–aldosterone system and subcutaneous resistance arteries: a randomized crossover study

Cited by 2 publications

References 0 publications

Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD

Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD

Amiloride lowers plasma TNF and interleukin-6 but not interleukin-17A in patients with hypertension and type 2 diabetes

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