Department of Medical Sciences, Nephrology and Dialysis Unit, Research Hospital "Casa Sollievo della Sofferenza" Foundation, San Giovanni Rotondo, Italy.
Department of Public Health, Chair of Nephrology, University of Naples Federico II, Naples, Italy.
Kidney Blood Press Res. 2024;49(1):812-820. doi: 10.1159/000540659. Epub 2024 Sep 6.
Physical exercise (PE) can regulate inflammation, cardiovascular health, sarcopenia, anaemia, and bone health in the chronic kidney disease (CKD) population. Experimental and clinical studies both help us better understand the mechanisms that underlie the beneficial effects of the exercise, especially in renal anaemia and CKD-mineral bone disorders (CKD-MBDs). Here, we summarize this evidence, exploring the biological pathways involved, locally released substances, and crosstalk between tissues, but also the shortcomings of current knowledge.
Anaemia: Both in healthy and CKD subjects, PE may mimic hypoxia, inhibiting PHDs; so hydroxylate HIF-α subunits may be translocated into the nucleus, resulting in dimerization of HIF-1α and HIF-1β, recruitment of p300 and CBP, and ultimately, binding to HREs at target genes to cause activation. However, in CKD subjects acute PE causes higher levels of lactate, leading to iron restriction by upregulating hepatic hepcidin expression, while chronic PE allows an increased lactate clearance and HIF-α and VEGFα levels, stimulating both erythropoiesis and angiogenesis.
CKD-MBD: PE may improve bone health decreasing bone resorption and increasing bone formation throughout at least three main pathways: (a) increasing osteoprotegerin and decreasing RANKL system; (b) decreasing cytokine levels; and (c) stimulating production of myokines and adipokines.
Future research needs to be defined to develop evidence-based exercise guidance to provide optimal benefit for CKD using exercise interventions as adjuvant therapy for CKD-related complications such as anaemia and CKD-MBD.
体育锻炼（PE）可以调节炎症、心血管健康、肌肉减少症、贫血和慢性肾脏病（CKD）患者的骨骼健康。实验和临床研究都有助于我们更好地理解运动有益作用的机制，特别是在肾脏性贫血和 CKD 矿物质骨代谢紊乱（CKD-MBD）方面。在这里，我们总结了这方面的证据，探讨了涉及的生物学途径、局部释放的物质以及组织之间的串扰，但也指出了当前知识的不足之处。
贫血：在健康人和 CKD 患者中，PE 可能模拟缺氧，抑制 PHDs；因此，HIF-α亚基可能被羟化并转移到细胞核中，导致 HIF-1α和 HIF-1β二聚体形成，招募 p300 和 CBP，最终与靶基因上的 HRE 结合，导致激活。然而，在 CKD 患者中，急性 PE 会导致更高水平的乳酸，通过上调肝脏铁调素表达导致铁限制，而慢性 PE 允许增加乳酸清除率和 HIF-α和 VEGFα水平，刺激红细胞生成和血管生成。
CKD-MBD：PE 可以通过至少三种主要途径改善骨骼健康，减少骨吸收并增加骨形成：（a）增加骨保护素并减少 RANKL 系统；（b）降低细胞因子水平；和（c）刺激肌因子和脂肪因子的产生。
需要进一步研究以制定循证运动指南，通过运动干预作为 CKD 相关并发症（如贫血和 CKD-MBD）的辅助治疗，为 CKD 患者提供最佳益处。
