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Extracellular fluid (ECF) potassium concentration ([K+]) is maintained by adaptations of kidney and skeletal muscle, responses heretofore studied separately. We aimed to determine how these organ systems work in concert to preserve ECF [K+] in male C57BL/6J mice fed a K+-deficient diet (0K) versus 1% K+ diet (1K) for 10 days (n = 5–6/group). During 0K feeding, plasma [K+] fell from 4.5 to 2 mM; hindlimb muscle (gastrocnemius and soleus) lost 28 mM K+ (from 115 ± 2 to 87 ± 2 mM) and gained 27 mM Na+ (from 27 ± 0.4 to 54 ± 2 mM). Doubling of muscle tissue [Na+] was not associated with inflammation, cytokine production or hypertension as reported by others. Muscle transporter adaptations in 0K- versus 1K-fed mice, assessed by immunoblot, included decreased sodium pump α2-β2 subunits, decreased K+-Cl− cotransporter isoform 3, and increased phosphorylated (p) Na+,K+,2Cl− cotransporter isoform 1 (NKCC1p), Ste20/SPS-1-related proline-alanine rich kinase (SPAKp), and oxidative stress-responsive kinase 1 (OSR1p) consistent with intracellular fluid (ICF) K+ loss and Na+ gain. Renal transporters’ adaptations, effecting a 98% reduction in K+ excretion, included two- to threefold increased phosphorylated Na+-Cl− cotransporter (NCCp), SPAKp, and OSR1p abundance, limiting Na+ delivery to epithelial Na+ channels where Na+ reabsorption drives K+ secretion; and renal K sensor Kir 4.1 abundance fell 25%. Mass balance estimations indicate that over 10 days of 0K feeding, mice lose ~48 μmol K+ into the urine and muscle shifts ~47 μmol K+ from ICF to ECF, illustrating the importance of the concerted responses during K+ deficiency. [ABSTRACT FROM AUTHOR]

Background: Losing or donating a kidney is associated with risks of developing hypertension and albuminuria. Few studies address mechanisms or interventions. We investigate potential benefits of a K+- alkali-enriched diet and the mechanisms underlying proteinuria., Methods: Male Sprague Dawley rats were fed either a 2% NaCl + 0.95% KCl diet (HNa-LK) or a 0.74% NaCl + 3% K+-alkali diet (HK-alk) for 3 wk prior to uninephrectomy then maintained on respective diets for 12 wk. Blood pressure (by tail-cuff), urine, blood and kidney proteins were analyzed Pre- and Post-uninephrectomy., Results: Pre-uninephrectomy, HK-alk vs. HNa-LK fed rats exhibited similar blood pressures and plasma [K+], [Na+], but lower proximal (NHE3, NBCe1, NaPi2) and higher distal (NCC, ENaC, pendrin) transporter abundance, a pattern facilitating K+ and HCO3- secretion. Post-uninephrectomy, single nephron GFR rose 50% and Li+ clearance doubled with both diets; in HK-alk vs HNa-LK: the rise in blood pressure was less and ammoniagenesis was lower, abundance of proximal tubule transporters remained lower, ENaC-α fell and NCCp rose consistent with K+ conservation. Post-uninephrectomy, independent of diet, albuminuria increased 8-fold and abundance of endocytic receptors was reduced (megalin by 44%, dab2 by 25-35%) and KIM-1 was increased., Conclusions: The K-alkali-enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing proximal Na+ transporters and increasing K+ -alkali secretion. Further, uninephrectomy associated proteinuria could be attributed, at least in part, to elevated SNGFR coupled to downregulation of megalin which reduced fractional protein endocytosis and Vmax., (Copyright © 2024 by the American Society of Nephrology.)

Chronic kidney disease is a debilitating condition associated with significant morbidity and mortality. In recent years, the kidney effects of incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), have garnered substantial interest in the management of type 2 diabetes and obesity. This review delves into the intricate interactions between the kidney, GLP-1RAs, and glucagon, shedding light on their mechanisms of action and potential kidney benefits. Both GLP-1 and glucagon, known for their opposing roles in regulating glucose homeostasis, improve systemic risk factors affecting the kidney, including adiposity, inflammation, oxidative stress, and endothelial function. Additionally, these hormones and their pharmaceutical mimetics may have a direct impact on the kidney. Clinical studies have provided evidence that incretins, including those incorporating glucagon receptor agonism, are likely to exhibit improved kidney outcomes. Although further research is necessary, receptor polypharmacology holds promise for preserving kidney function through eliciting vasodilatory effects, influencing volume and electrolyte handling, and improving systemic risk factors.

Extracellular fluid (ECF) potassium concentration ([K + ]) is maintained by adaptations of kidney and skeletal muscle, responses heretofore studied separately. We aimed to determine how these organ systems work in concert to preserve ECF [K + ] in male C57BL/6J mice fed a K + -deficient diet (0K) versus 1% K + diet (1K) for 10 days ( n = 5-6/group). During 0K feeding, plasma [K + ] fell from 4.5 to 2 mM; hindlimb muscle (gastrocnemius and soleus) lost 28 mM K + (from 115 ± 2 to 87 ± 2 mM) and gained 27 mM Na + (from 27 ± 0.4 to 54 ± 2 mM). Doubling of muscle tissue [Na + ] was not associated with inflammation, cytokine production or hypertension as reported by others. Muscle transporter adaptations in 0K- versus 1K-fed mice, assessed by immunoblot, included decreased sodium pump α2-β2 subunits, decreased K + -Cl - cotransporter isoform 3, and increased phosphorylated (p) Na + ,K + ,2Cl - cotransporter isoform 1 (NKCC1p), Ste20/SPS-1-related proline-alanine rich kinase (SPAKp), and oxidative stress-responsive kinase 1 (OSR1p) consistent with intracellular fluid (ICF) K + loss and Na + gain. Renal transporters' adaptations, effecting a 98% reduction in K + excretion, included two- to threefold increased phosphorylated Na + -Cl - cotransporter (NCCp), SPAKp, and OSR1p abundance, limiting Na + delivery to epithelial Na + channels where Na + reabsorption drives K + secretion; and renal K sensor Kir 4.1 abundance fell 25%. Mass balance estimations indicate that over 10 days of 0K feeding, mice lose ~48 μmol K + into the urine and muscle shifts ~47 μmol K + from ICF to ECF, illustrating the importance of the concerted responses during K + deficiency.