Daily dietary potassium (K+) intake may be as large as the extracellular K+ pool. To avoid acute hyperkalemia, rapid removal of K+ from the extracellular space is essential. This is achieved by translocating K+ into cells and increasing urinary K+ excretion. Emerging data now indicate that the renal thiazide-sensitive NaCl cotransporter (NCC) is critically involved in this homeostatic kaliuretic response. This suggests that the early distal convoluted tubule (DCT) is a K+ sensor that can modify sodium (Na+) delivery to downstream segments to promote or limit K+ secretion. K+ sensing is mediated by the basolateral K+ channels Kir4.1/5.1, a capacity that the DCT likely shares with other nephron segments. Thus, next to K+-induced aldosterone secretion, K+ sensing by renal epithelial cells represents a second feedback mechanism to control K+ balance. NCC's role in K+ homeostasis has both physiological and pathophysiological implications. During hypovolemia, NCC activation by the renin-angiotensin system stimulates Na+ reabsorption while preventing K+ secretion. Conversely, NCC inactivation by high dietary K+ intake maximizes kaliuresis and limits Na+ retention, despite high aldosterone levels. NCC activation by a low-K+ diet contributes to salt-sensitive hypertension. K+-induced natriuresis through NCC offers a novel explanation for the antihypertensive effects of a high-K+ diet. A possible role for K+ in chronic kidney disease is also emerging, as epidemiological data reveal associations between higher urinary K+ excretion and improved renal outcomes. This comprehensive review will embed these novel insights on NCC regulation into existing concepts of K+ homeostasis in health and disease.

中文翻译：

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肾脏NaCl共转运蛋白的调节及其在钾稳态中的作用。

每日饮食中的钾（K +）摄入量可能与细胞外K +库一样大。为了避免急性高钾血症，从细胞外空间快速清除K +是必不可少的。这可以通过将K +转运到细胞中并增加尿K +排泄来实现。现在，越来越多的数据表明，肾脏对噻嗪类敏感的NaCl共转运蛋白（NCC）严重参与了这种稳态的利尿剂反应。这表明早期的远端旋回小管（DCT）是一个K +传感器，可以修改钠（Na +）向下游节段的传递，以促进或限制K +分泌。K +感测由基底外侧K +通道Kir4.1 / 5.1介导，DCT可能与其他肾单位段共享这种能力。因此，除了由K +诱导的醛固酮分泌外，肾上皮细胞对K +的传感代表了控制K +平衡的第二种反馈机制。NCC在K +稳态中的作用具有生理和病理生理意义。在血容量不足时，肾素-血管紧张素系统激活NCC会刺激Na +重吸收，同时阻止K +分泌。相反，尽管醛固酮水平高，但高饮食K +摄入会使NCC失活最大程度地利尿，并限制Na +保留。低钾饮食会激活NCC导致对盐敏感的高血压。通过NCC诱导的K +排钠为高K +饮食的降压作用提供了新颖的解释。由于流行病学数据显示，尿K +排泄量增加与肾脏预后改善之间的相关性，K +在慢性肾脏疾病中的可能作用也正在显现。这项全面的综述将把有关NCC调节的这些新颖见解嵌入到健康和疾病中K +稳态的现有概念中。