肥胖相关肾小球病发病机制和临床治疗的研究进展

    The pathogenesis, clinical treatment and research progress of obesity-related glomerulopathy disease

    • 摘要: 肥胖已成为世界性的流行病,肥胖人群的比例于近十年来不断升高。肥胖作为多种疾病的危险因素,影响全身多个器官,其中包括肾脏。一种与肥胖相关的肾病,肥胖相关肾小球病(obesity-related glomerulopathy,ORG)逐渐开始被人们认识并重视。肥胖、高体重指数是诱发慢性肾脏病(chronic kidney disease,CKD)的最强危险因素之一。在肥胖的个体中,肾脏会发生代偿性超滤,以满足体重增加后的高代谢需求。肾小球内压力升高会加重肾脏损害,并增加发展为ORG及CKD的风险。既往对ORG的发病机制的研究结果尚不全面,已知的主要机制包括肾小球血流动力学异常、肾素-血管紧张素-醛固酮系统激活、脂代谢紊乱、脂肪细胞因子紊乱、胰岛素抵抗、微炎症作用等。ORG的临床表现不典型,虽然大多数患者临床上只单纯表现为稳定或缓慢进展的蛋白尿,但多达三分之一的患者会发展为进行性肾衰竭和终末期肾病。故早发现早治疗,可显著提高患者的预后及生活质量。ORG的治疗方式目前包括:生活方式干预、药物治疗、减肥手术;减轻体重是治疗的核心,减轻体重的不同治疗方式可能会带来不可预知的后果。针对脂质代谢的新疗法、增强机体对胰岛素敏感性的药物,及特定靶向治疗方案,都是未来研究的热点和治疗方式的新希望。本文将主要介绍论述肥胖及ORG的流行病学、ORG的病理学改变、现已发现的主要发病机制及目前和未来可创新突破的治疗方法。

       

      Abstract: Obesity has become a worldwide epidemic, and the proportion of obese people has been increasing in the last decade. Obesity is a risk factor for many diseases. It affects multiple organs throughout the body, including kidney. Obesity-related glomerulopathy,(ORG) a type of obesity-related kidney disease, has been gradually recognized and valued. Obesity and high body mass index are one of the strongest risk factors for chronic kidney diseases(CKD). In obese individuals, kidneys undergo compensatory ultrafiltration to meet the high metabolic demands of weight gain. Increased pressure in the glomerulus will exacerbate kidney damage. It increases the risk of developing ORG and CKD. Previous studies on the pathogenesis of ORG have not been comprehensive, and the main known mechanisms include abnormal glomerular hemodynamics, activation of the renin-angiotensin-aldosterone system (RAAS), lipid metabolism disorders, adipocytokine disorders, insulin resistance, microinflammation, etc. The clinical presentation of ORG is atypical. Although most patients only present with stable or slowly progressive proteinuria clinically, up to one-third of patients develop progressive renal failure and end-stage renal disease. Therefore, early detection and early treatment can significantly improve the prognosis and quality of life of ORG patients. Treatment options currently include lifestyle interventions, medications, and bariatric surgery. Weight loss is central to treatment, and different treatments for weight loss can have unpredictable consequences. New therapies for lipid metabolism, drugs to enhance the body's sensitivity to insulin, and specific targeted therapies are all hot spots for future research and new hopes for therapeutic approaches. This review introduces the epidemiology of obesity and ORG, the pathological changes of ORG, the main pathogenesis discovered, and the current and future innovative treatment methods.

       

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