Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom.
Antioxid Redox Signal. 2021 Dec 10;35(17):1426-1448. doi: 10.1089/ars.2020.8184. Epub 2021 Jul 30.
Chronic kidney disease (CKD) can be regarded as a burden of lifestyle disease that shares common underpinning features and risk factors with the aging process; it is a complex constituted by several adverse components, including chronic inflammation, oxidative stress, early vascular aging, and cellular senescence. A systemic approach to tackle CKD, based on mitigating the associated inflammatory, cell stress, and damage processes, has the potential to attenuate the effects of CKD, but it also preempts the development and progression of associated morbidities. In effect, this will enhance health span and compress the period of morbidity. Pharmacological, nutritional, and potentially lifestyle-based interventions are promising therapeutic avenues to achieve such a goal. In the present review, currents concepts of inflammation and oxidative damage as key patho-mechanisms in CKD are addressed. In particular, potential beneficial but also adverse effects of different systemic interventions in patients with CKD are discussed. Senotherapeutics, the nuclear factor erythroid 2-related factor 2-kelch-like ECH-associated protein 1 (NRF2-KEAP1) signaling pathway, the endocrine klotho axis, inhibitors of the sodium-glucose cotransporter 2 (SGLT2), and live bio-therapeutics have the potential to reduce the burden of CKD and improve quality of life, as well as morbidity and mortality, in this fragile high-risk patient group. 35, 1426-1448.
慢性肾脏病 (CKD) 可以被视为一种生活方式病的负担，它与衰老过程具有共同的潜在特征和危险因素；它是由几个不利因素构成的复杂疾病，包括慢性炎症、氧化应激、早期血管老化和细胞衰老。基于减轻相关炎症、细胞应激和损伤过程的系统性方法来解决 CKD 问题，有可能减轻 CKD 的影响，但也可以预防相关疾病的发生和进展。实际上，这将延长健康寿命并压缩发病期。基于药理学、营养和潜在的生活方式干预的方法是实现这一目标的有前途的治疗途径。在本综述中，我们讨论了炎症和氧化损伤作为 CKD 关键病理机制的现有概念。特别是，我们讨论了不同系统性干预措施对 CKD 患者的潜在有益和不利影响。衰老治疗学、核因子红细胞 2 相关因子 2-克拉夫特样 ECH 相关蛋白 1 (NRF2-KEAP1) 信号通路、内分泌 klotho 轴、钠-葡萄糖共转运蛋白 2 (SGLT2) 抑制剂和活体生物治疗具有减轻 CKD 负担的潜力，并提高该脆弱高危患者群体的生活质量以及降低发病率和死亡率。35, 1426-1448.
