Chronic kidney disease (CKD) causes salt-sensitive hypertension that is often resistant to treatment and contributes to the progression of kidney injury and cardiovascular disease. A better understanding of the mechanisms contributing to salt-sensitive hypertension in CKD is essential to improve these outcomes. This review critically explores these mechanisms by focusing on how CKD affects distal nephron sodium (Na⁺) reabsorption. CKD causes glomerulotubular imbalance with reduced proximal Na⁺ reabsorption and increased distal Na⁺ delivery and reabsorption. Aldosterone secretion further contributes to distal Na⁺ reabsorption in CKD and is not only mediated by renin and potassium, but also by metabolic acidosis, endothelin-1, and vasopressin. CKD also activates the intrarenal renin-angiotensin system (RAS) generating intratubular angiotensin II to promote distal Na⁺ reabsorption. High dietary Na⁺ intake in CKD contributes to Na⁺ retention by an aldosterone-independent activation of the mineralocorticoid receptor mediated through Rac1. High dietary Na⁺ also produces an inflammatory response mediated by T helper 17 cells and cytokines increasing distal Na⁺ transport. CKD is often accompanied by proteinuria, which contains plasmin capable of activating the epithelial Na⁺ channel. Thus, CKD causes both local and systemic changes that together promote distal nephron Na⁺ reabsorption and salt-sensitive hypertension. Future studies should address remaining knowledge gaps, including the relative contribution of each mechanism, the influence of sex, differences between stages and etiologies of CKD, and the clinical relevance of experimentally identified mechanisms. Several pathways offer opportunities for intervention, including with dietary Na⁺ reduction, distal diuretics, RAS-inhibitors, mineralocorticoid receptor antagonists, and potassium or hydrogen ion binders.

中文翻译：

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慢性肾脏病中的盐敏感性高血压：肾小管远端机制

慢性肾脏病（CKD）引起对盐敏感的高血压，通常对治疗有抵抗力，并导致肾脏损伤和心血管疾病的进展。更好地了解导致CKD盐敏感性高血压的机制对于改善这些结果至关重要。这篇综述着重于CKD如何影响远端肾单位钠（Na ⁺）重吸收，从而探索了这些机制。CKD引起肾小球小管失衡，降低了近端Na ^+的吸收，并增加了远端Na ^+的释放和吸收。醛固酮分泌进一步促进远端Na ⁺在CKD中的重吸收不仅由肾素和钾介导，而且还由代谢性酸中毒，内皮素-1和加压素介导。CKD还激活肾内肾素-血管紧张素系统（RAS），生成肾小管内血管紧张素II，促进远端Na ⁺重吸收。CKD中高饮食中Na ^+的摄入通过Rac1介导的盐皮质激素受体的醛固酮非依赖性激活而有助于Na ⁺保留。高饮食中的Na ⁺还会产生由T辅助细胞17和细胞因子介导的炎症反应，从而增加远端Na ^+的转运。CKD常伴有蛋白尿，蛋白尿中含有能激活上皮Na ^+的纤溶酶渠道。因此，CKD引起局部和全身性改变，共同促进远端肾单位对Na ^+的重吸收和盐敏感性高血压。未来的研究应解决剩余的知识空白，包括每种机制的相对贡献，性别的影响，CKD的阶段和病因学之间的差异以及实验确定的机制的临床相关性。几种途径提供了干预的机会，包括减少饮食中的Na ⁺含量，利尿剂的远端使用，RAS抑制剂，盐皮质激素受体拮抗剂以及钾或氢离子结合剂。