Hyperkalemia and blood pressure regulation.
Hyperkalemia and blood pressure regulation.
复制标题
DOI：
10.1093/ndt/gfz218
复制
发表时间：
2019-12
期刊：
影响因子：
--
通讯作者：
K. Mutig;S. Bachmann
中科院分区：
文献类型：
--
作者：
K. Mutig;S. Bachmann
高血压在普通人群中很常见。由于存在潜在的危及生命的并发症，如心脏骤停，高血钾高血压患者的管理是具有挑战性的。慢性高钾血症通常与肾脏排泄过量钾离子(K+)的能力受损有关。这可能是指慢性肾脏疾病或某些药物干预，包括广泛使用的肾素-血管紧张素-醛固酮系统和钙调神经磷酸酶抑制剂。了解肾脏适应高钾血症的内在机制对于选择治疗策略至关重要。家族性高血钾高血压综合征(FHHt)是研究高血压与高钾血症的经典模型，对FHHt综合征的研究具有重要意义。FHHt可由几个基因的突变引起，所有这些基因都导致肾脏远端肾单位中无赖氨酸激酶(WNKS)的过度活动。WNKs已被认为是调节肾脏钠离子(Na+)和K+处理的关键信号酶，使其能够对由于饮食中钾摄入量或疾病的变化而导致的系统钾稳态变化做出适应性反应。WNK信号通路招募了一个复杂的蛋白质网络，介导不同WNK亚型对相关的Na+或K+转运蛋白的催化和非催化作用。在这篇综述文章中，我们总结了在理解WNK信号方面的最新进展。介绍了肾脏对高血钾条件适应的现有模型的最新进展。对血压调节的后果进行了讨论。WNKS或其底物的药理学靶向为控制高血压和预防高钾血症提供了有希望的选择。
Hypertension is common in the general population. Management of hypertensive patients at risk of hyperkalemia is challenging due to potential life-threatening complications such as cardiac arrest. Chronic hyperkalemia is often associated with impaired renal ability to excrete excessive potassium ions (K+). This may refer to chronic kidney disease or certain pharmacological interventions, including broadly used renin-angiotensin-aldosterone system and calcineurin inhibitors. Understanding the intrinsic mechanisms permitting kidney adaptations to hyperkalemia is critical for choosing therapeutic strategies. Valuable insights were obtained from the analysis of familial hyperkalemic hypertension (FHHt) syndrome, which became a classic model for coincidence of high blood pressure and hyperkalemia. FHHt can be caused by mutations in several genes, all of them resulting in excessive activity of with-no-lysine kinases (WNKs) in the distal nephron of the kidney. WNKs have been increasingly recognized as key signalling enzymes in the regulation of renal sodium ions (Na+) and K+ handling, enabling adaptive responses to systemic shifts of potassium homoeostasis consequent to variations in dietary potassium intake or disease. The WNK signalling pathway recruits a complex protein network mediating catalytic and non-catalytic effects of distinct WNK isoforms on relevant Na+- or K+-transporting proteins. In this review article, we summarize recent progress in understanding WNK signalling. An update of available models for renal adaptation to hyperkalemic conditions is presented. Consequences for blood pressure regulation are discussed. Pharmacological targeting of WNKs or their substrates offers promising options to manage hypertension while preventing hyperkalemia.