Dutta Abhi, Chakraborty Sanchari, Roy Antara, Mittal Anupam, Basak Trayambak
School of Biosciences and Bioengineering, Indian Institute of Technology (IIT), Mandi, Himachal Pradesh, India.
Department of Translational and Regenerative Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Nephrol Dial Transplant. 2025 Jan 13. doi: 10.1093/ndt/gfaf009.
Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (Macrophages, Monocytes, and T-cells) infiltration and myofibroblast activation. An inflammatory to fibrotic transition corresponds with macrophage transition (M1-M2) associated with increased TGF-β response. Chronic inflammation disrupts hemodynamic pathways, leading to imbalanced oxidative stress and the production of cytokines and growth factors that promote fibrotic stimulation, contributing to pathological cardiorenal remodeling. The inflammatory response paves the pre-fibrotic cardiorenal niche and drives subsequent fibrotic remodeling by activated myofibroblasts. A fibrotic cardiorenal response in CRS is characterized by increased and degradation-resistant deposition of extracellular proteins especially fibrillar Collagen -I, -III, -V, and non-fibrillar Collagen-IV by active myofibroblasts. Recent advances in basic research animal models of CRS have advanced the knowledge of cardiorenal fibrosis. However, a significant need for clinical applications, trials, and evaluation is still needed. Circulating biomarkers like procollagen peptides and TGF-β have clinically been associated with cardiorenal fibrosis diagnosis in CRS. Treatments targeting the fibrotic pathways have also shown efficacy in amelioration of cardiorenal fibrosis in preclinical models. Recent combination therapies targeting multiple fibrotic pathways have been shown to offer promising results. Understanding the heterogenic pathological progression and fibrogenesis could identify novel therapeutic approaches for clinical CRS diagnosis and treatment.
心肾综合征（CRS）表现为心脏和肾脏之间复杂的功能失调相互作用，其特征是心肾炎症和纤维化。与其他器官不同，心肾损伤的修复过程包括一个以增殖和多倍体化为特征的再生阶段，随后是纤维化的致病阶段。在CRS中，急性或慢性心肾损伤会导致炎症反应亢进和纤维化重塑，这与损伤介导的免疫细胞（巨噬细胞、单核细胞和T细胞）浸润以及肌成纤维细胞活化有关。炎症向纤维化的转变与巨噬细胞转变（M1-M2）相关，伴随着转化生长因子-β反应增强。慢性炎症会破坏血流动力学途径，导致氧化应激失衡以及细胞因子和生长因子的产生，这些因子会促进纤维化刺激，从而导致病理性心肾重塑。炎症反应为纤维化前期的心肾微环境奠定基础，并由活化的肌成纤维细胞驱动随后的纤维化重塑。CRS中的纤维化心肾反应的特征是细胞外蛋白尤其是活性肌成纤维细胞产生的抗降解的I型、III型、V型纤维状胶原蛋白和IV型非纤维状胶原蛋白沉积增加。CRS基础研究动物模型的最新进展增进了对心肾纤维化的认识。然而，临床应用、试验和评估仍有很大需求。循环生物标志物如前胶原肽和转化生长因子-β在临床上已与CRS的心肾纤维化诊断相关联。针对纤维化途径的治疗在临床前模型中也显示出改善心肾纤维化的功效。最近针对多种纤维化途径的联合疗法已显示出有希望的结果。了解异质性病理进展和纤维化形成可以为临床CRS诊断和治疗确定新的治疗方法。
