Savira Feby, Magaye Ruth, Liew Danny, Reid Christopher, Kelly Darren J, Kompa Andrew R, Sangaralingham S Jeson, Burnett John C, Kaye David, Wang Bing H
Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Br J Pharmacol. 2020 Jul;177(13):2906-2922. doi: 10.1111/bph.15065. Epub 2020 May 13.
Cardiorenal syndrome (CRS) is a multi-organ disease, encompassing heart, kidney and vascular system dysfunction. CRS is a worldwide problem, with high morbidity, mortality, and inflicts a significant burden on the health care system. The pathophysiology is complex, involving interactions between neurohormones, inflammatory processes, oxidative stress and metabolic derangements. Therapies remain inadequate, mainly comprising symptomatic care with minimal prospect of full recovery. Challenges include limiting the contradictory effects of multi-organ targeted drug prescriptions and continuous monitoring of volume overload. Novel strategies such as multi-organ transplantation and innovative dialysis modalities have been considered but lack evidence in the CRS context. The adjunct use of pharmaceuticals targeting alternative pathways showing positive results in preclinical models also warrants further validation in the clinic. In recent years, studies have identified the involvement of gut dysbiosis, uraemic toxin accumulation, sphingolipid imbalance and other unconventional contributors, which has encouraged a shift in the paradigm of CRS therapy.
心肾综合征(CRS)是一种多器官疾病,包括心脏、肾脏和血管系统功能障碍。CRS是一个全球性问题,具有高发病率、高死亡率,并给医疗保健系统带来巨大负担。其病理生理学很复杂,涉及神经激素、炎症过程、氧化应激和代谢紊乱之间的相互作用。治疗方法仍然不足,主要包括对症治疗,完全康复的前景极小。挑战包括限制多器官靶向药物处方的矛盾作用以及持续监测容量超负荷。多器官移植和创新透析模式等新策略已被考虑,但在CRS背景下缺乏证据。在临床前模型中显示出积极结果的针对替代途径的药物辅助使用也需要在临床上进一步验证。近年来,研究已经确定肠道微生物群失调、尿毒症毒素积累、鞘脂失衡和其他非常规因素的参与,这促使CRS治疗模式发生转变。