Wu Aihua, Wolley Martin J, Mayr Hannah L, Cheng Lei, Cowley Diane, Li Bo, Campbell Katrina L, Terker Andrew S, Ellison David H, Welling Paul A, Fenton Robert A, Stowasser Michael
Endocrine Hypertension Research Centre, University of Queensland Frazer Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia.
Department of Nephrology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Kidney Int Rep. 2023 Mar 27;8(6):1201-1212. doi: 10.1016/j.ekir.2023.03.011. eCollection 2023 Jun.
The putative "renal-K switch" mechanism links dietary potassium intake with sodium retention and involves activation of the sodium chloride (NaCl) cotransporter (NCC) in the distal convoluted tubule in response to low potassium intake, and suppression in response to high potassium intake. This study examined NCC abundance and phosphorylation (phosphorylated NCC [pNCC]) in urinary extracellular vesicles (uEVs) isolated from healthy adults on a high sodium diet to determine tubular responses to alteration in potassium chloride (KCl) intake.
Healthy adults maintained on a high sodium (∼4.5 g [200 mmol]/d) low potassium (∼2.3 g [60 mmol]/d) diet underwent a 5-day run-in period followed by a crossover study, with 5-day supplementary KCl (active phase, Span-K 3 tablets (potassium 24 mmol) thrice daily) or 5-day placebo administrated in random order and separated by 2-day washout. Ambulatory blood pressure (BP) and biochemistries were assessed, and uEVs were analyzed by western blotting.
Among the 18 participants who met analysis criteria, supplementary KCl administration (vs. placebo) was associated with markedly higher levels of plasma potassium and 24-hour urine excretion of potassium, chloride, and aldosterone. KCl supplementation was associated with lower uEV levels of NCC (median fold change = 0.74 [0.30-1.69], < 0.01) and pNCC (fold change = 0.81 [0.19-1.75], < 0.05). Plasma potassium inversely correlated with uEV NCC (R = 0.11, = 0.05).
The lower NCC and pNCC in uEVs in response to oral KCl supplementation provide evidence to support the hypothesis of a functional "renal-K switch" in healthy human subjects.
假定的“肾 - 钾开关”机制将饮食中的钾摄入与钠潴留联系起来，涉及在低钾摄入时激活远端曲管中的氯化钠（NaCl）共转运体（NCC），以及在高钾摄入时抑制该转运体。本研究检测了从高钠饮食的健康成年人中分离出的尿细胞外囊泡（uEVs）中NCC的丰度和磷酸化水平（磷酸化NCC [pNCC]），以确定肾小管对氯化钾（KCl）摄入量改变的反应。
维持高钠（约4.5 g [200 mmol]/天）低钾（约2.3 g [60 mmol]/天）饮食的健康成年人经过5天的导入期，随后进行交叉研究，随机顺序给予5天的补充KCl（活跃期，Span - K 3片（钾24 mmol），每日三次）或5天的安慰剂，中间间隔2天的洗脱期。评估动态血压（BP）和生化指标，并通过蛋白质印迹法分析uEVs。
在符合分析标准的18名参与者中，补充KCl（与安慰剂相比）与血浆钾水平以及钾、氯和醛固酮的24小时尿排泄量显著升高有关。补充KCl与uEVs中较低水平的NCC（中位数倍数变化 = 0.74 [0.30 - 1.69]，< 0.01）和pNCC（倍数变化 = 0.81 [0.19 - 1.75]，< 0.05）相关。血浆钾与uEV NCC呈负相关（R = 0.11， = 0.05）。
口服补充KCl后uEVs中NCC和pNCC水平降低，为支持健康人类受试者中功能性“肾 - 钾开关”假说提供了证据。
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