Obesity-related glomerulopathy: how it happens and future perspectives

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.