Lee-Boey Jian-Wen Samuel, Tan Jia-Kai, Lim Zhan-Foong, Zaccardi Francesco, Khunti Kamlesh, Ezzati Majid, Gregg Edward W, Lim Lee-Ling
Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK.
Diabet Med. 2025 Jun;42(6):e70042. doi: 10.1111/dme.70042. Epub 2025 Apr 14.
Obesity-related glomerulopathy (ORG) is an emerging complication of excess adiposity. Its incidence rises alongside the obesity pandemic. Up to 40% of individuals can be affected by ORG, irrespective of the status of glomerular filtration rate and albuminuria. ORG is a distinct histological diagnosis based on kidney biopsy, showing classical features of an enlarged glomerulus with and without focal segmental glomerulosclerosis in the perihilar region seen with all categories of obesity. About 10% of individuals with ORG may progress to end-stage kidney disease. The invasive nature of kidney biopsy highlights the need for non-invasive biomarkers for improved screening, diagnosis and risk prediction of ORG. These biomarkers may narrow the gaps in the management of ORG by improving: (1) screening, diagnosis and differentiation of ORG from non-ORG conditions; (2) risk prediction and stratification of individuals at risk of progression to end-stage kidney disease including the detection of trajectories of progression; (3) monitoring of treatment safety and effectiveness and (4) development of novel therapeutic targets. In the present review, we discussed the pathophysiology, emerging biomarkers (such as kidney injury molecule-1 [KIM-1], uromodulin, klotho, circulating microRNA-21 [miR-21]) and future treatment strategies (metabolic surgery, sodium-glucose cotransporter-2 inhibitors, incretin-based therapy and non-steroidal mineralocorticoid antagonists) of ORG.
肥胖相关肾小球病（ORG）是肥胖症日益常见的一种并发症。其发病率随着肥胖症的流行而上升。高达40%的个体可能受到ORG的影响，而不论其肾小球滤过率和蛋白尿状况如何。ORG是一种基于肾活检的独特组织学诊断，表现为肾小球增大的典型特征，在各类肥胖患者中均可见到肾门周围区域有或无局灶节段性肾小球硬化。约10%的ORG患者可能进展为终末期肾病。肾活检具有侵入性，这凸显了需要非侵入性生物标志物来改善ORG的筛查、诊断和风险预测。这些生物标志物可通过改善以下方面来缩小ORG管理中的差距：（1）ORG与非ORG情况的筛查、诊断和鉴别；（2）对有进展为终末期肾病风险的个体进行风险预测和分层，包括检测进展轨迹；（3）监测治疗安全性和有效性；（4）开发新的治疗靶点。在本综述中，我们讨论了ORG的病理生理学、新兴生物标志物（如肾损伤分子-1 [KIM-1]、尿调节蛋白、klotho、循环微小RNA-21 [miR-21]）以及未来的治疗策略（代谢手术、钠-葡萄糖协同转运蛋白-2抑制剂、肠促胰岛素疗法和非甾体类盐皮质激素拮抗剂）。
