Obesity-related glomerulopathy: How it happens and future perspectives.

Francesco Zaccardi, Lee-Ling Lim, Majid Ezzati, Kamlesh Khunti, Edward W Gregg, Jian-Wen Samuel Lee-Boey, Jia-Kai Tan, Zhan-Foong Lim

Journal: Diabetic medicine : a journal of the British Diabetic Association 2025;42(6):e70042

PMID: 40226862

Abstract

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.

© 2025 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Address: Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.; Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK.; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; School of Population Health, Royal College of Surgeons of Ireland, Dublin, Ireland.; Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China.; Asia Diabetes Foundation, Hong Kong, SAR, China.; Baker Heart and Diabetes Institute, Melbourne, Australia.
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