Nehus Edward, Mitsnefes Mark
Department of Pediatrics, West Virginia University School of Medicine Charleston Campus, Charleston, WV, 25314, USA.
Institute for Academic Medicine, Charleston Area Medical Center, Charleston, WV, USA.
Pediatr Nephrol. 2025 Jun;40(6):1879-1893. doi: 10.1007/s00467-024-06623-y. Epub 2024 Dec 16.
Herein, we review the devastating consequences of the worldwide obesity epidemic on kidney health and outcomes. We submit that the obesity epidemic is the most pressing public health crisis facing the nephrology community today. A historical approach has been undertaken, wherein major breakthroughs in the recognition and understanding of obesity-related kidney disease (ORKD) are highlighted. We begin with a description of the worldwide obesity epidemic followed by an account of the discovery and characterization of ORKD. A detailed summary of the pathophysiology of ORKD disease is presented, wherein we set forth the following two propositions: first, ORKD is due to a maladaptive response to caloric surplus; and second, this maladaptive response causes kidney damage via hemodynamic (hyperfiltration), hormonal (adipokine dysregulation), and lipotoxic pathways. Each of these pathways is described, with particular emphasis on the relatively recent discovery that the final stage of cellular injury in ORKD is mitochondrial oxidative damage. The prevention and treatment of ORKD are then discussed, including environmental, behavioral, pharmacologic, and surgical options. Finally, we conclude with suggestions for future research to improve early recognition and treatment of ORKD.
在此，我们回顾全球肥胖流行对肾脏健康及预后造成的灾难性后果。我们认为，肥胖流行是当今肾脏病学界面临的最紧迫的公共卫生危机。我们采用了一种历史研究方法，着重介绍了在肥胖相关肾病（ORKD）的认识和理解方面取得的重大突破。我们首先描述全球肥胖流行情况，接着阐述ORKD的发现及特征。文中详细总结了ORKD的病理生理学，提出以下两个观点：其一，ORKD是对热量过剩的一种适应性不良反应；其二，这种适应性不良反应通过血流动力学（超滤过）、激素（脂肪因子失调）和脂毒性途径导致肾脏损伤。文中对每条途径都进行了描述，特别强调了相对较新的发现，即ORKD细胞损伤的最后阶段是线粒体氧化损伤。随后讨论了ORKD的预防和治疗方法，包括环境、行为、药物和手术方面的选择。最后，我们给出了未来研究的建议，以改善ORKD的早期识别和治疗。
