PDF(Pubmed)
Abstract：
Cardiorenal syndrome type 3 (CRS3) is defined as acute kidney injury (AKI)-induced acute cardiac dysfunction, characterized by high morbidity and mortality. CRS3 often occurs in elderly patients with AKI who need intensive care. Approximately 70% of AKI patients develop into CRS3. CRS3 may also progress towards chronic kidney disease (CKD) and chronic cardiovascular disease (CVD). However, there is currently no effective treatment. Although the major intermediate factors that can mediate cardiac dysfunction remain elusive, recent studies have summarized the AKI biomarkers, identified direct mechanisms, including mitochondrial dysfunction, inflammation, oxidative stress, apoptosis and activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS), inflammasome, as well as indirect mechanisms such as fluid overload, electrolyte imbalances, acidemia and uremic toxins, which are involved in the pathophysiological changes of CRS3. This study reviews the main pathological characteristics, underlying molecular mechanisms, and potential therapeutic strategies of CRS3. Mitochondrial dysfunction and inflammatory factors have been identified as the key initiators and abnormal links between the impaired heart and kidney, which contribute to the formation of a vicious circle, ultimately accelerating the progression of CRS3. Therefore, targeting mitochondrial dysfunction, antioxidants, Klotho, melatonin, gene therapy, stem cells, exosomes, nanodrugs, intestinal microbiota and Traditional Chinese Medicine may serve as promising therapeutic approaches against CRS3.
摘要：
心肾综合征3型（CRS3）定义为急性肾损伤（AKI）引起的急性心功能不全，具有高发病率和高死亡率的特点。CRS3通常发生在需要重症监护的老年AKI患者中。大约70%的AKI患者发展成CRS3。CRS3也可能进展为慢性肾病(CKD)和慢性心血管疾病(CVD)。然而,目前没有有效的治疗方法。尽管可以介导心功能不全的主要中间因素仍然难以捉摸，最近的研究总结了AKI生物标志物，确定的直接机制，包括线粒体功能障碍,炎症,氧化应激，交感神经系统（SNS）和肾素-血管紧张素-醛固酮系统（RAAS）的凋亡和激活，炎性体,以及流体过载等间接机制，电解质失衡，酸血症和尿毒症毒素，参与了CRS3的病理生理变化。本研究回顾了主要病理特征，潜在的分子机制，以及CRS3的潜在治疗策略。线粒体功能障碍和炎症因子已被确定为心脏和肾脏受损之间的关键启动和异常联系，这有助于形成恶性循环，最终加速CRS3的进展。因此,靶向线粒体功能障碍，抗氧化剂,Klotho,褪黑激素,基因治疗,干细胞,外泌体,纳米药物，肠道微生物群和中药可能是针对CRS3的有希望的治疗方法。
