Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, Rajasthan, India.
Division of Nephrology, Department of Internal Medicine IV, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany.
Arch Physiol Biochem. 2022 Aug;128(4):1024-1038. doi: 10.1080/13813455.2020.1745851. Epub 2020 Mar 30.
Liver and kidney are vital organs that maintain homeostasis and injury to either of them triggers pathogenic pathways affecting the other. For example, non-alcoholic fatty liver disease (NAFLD) promotes the progression of chronic kidney disease (CKD), vice versa acute kidney injury (AKI) endorses the induction and progression of liver dysfunction. Progress in clinical and basic research suggest a role of excessive fructose intake, insulin resistance, inflammatory cytokines production, activation of the renin-angiotensin system, redox imbalance, and their impact on epigenetic regulation of gene expression in this context. Recent developments in experimental and clinical research have identified several biochemical and molecular pathways for AKI-liver interaction, including altered liver enzymes profile, metabolic acidosis, oxidative stress, activation of inflammatory and regulated cell death pathways. This review focuses on the current preclinical and clinical findings on kidney-liver crosstalk in NAFLD-CKD and AKI-liver dysfunction settings and highlights potential molecular mechanisms and therapeutic targets.
肝脏和肾脏是维持体内平衡的重要器官，其中任何一个器官受到损伤都会触发影响另一个器官的致病途径。例如，非酒精性脂肪性肝病（NAFLD）会促进慢性肾脏病（CKD）的进展，反之亦然，急性肾损伤（AKI）会促进肝功能障碍的诱导和进展。临床和基础研究的进展表明，过量摄入果糖、胰岛素抵抗、炎性细胞因子产生、肾素-血管紧张素系统的激活、氧化还原失衡及其对基因表达的表观遗传调控在这方面起着重要作用。实验和临床研究的最新进展确定了 AKI-肝相互作用的几种生化和分子途径，包括改变的肝酶谱、代谢性酸中毒、氧化应激、炎性和调控性细胞死亡途径的激活。这篇综述重点介绍了目前关于 NAFLD-CKD 和 AKI-肝功能障碍背景下肾-肝相互作用的临床前和临床研究结果，并强调了潜在的分子机制和治疗靶点。
