Glomerular alteration in diabetic kidney disease: from morphology to metabolism

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. The glomerulus is the primary site of injury in DKD progression. Pathologically, the integrity of the glomerular filtration barrier is disrupted, characterized by podocyte process fusion and detachment, glomerular basement membrane thickening, and reduction of the endothelial cell glycocalyx. These disruptions result in albuminuria due to impaired function of glomerular selective filtration. Additionally, mesangial expansion driven by mesangial cell proliferation and excessive mesangial matrix accumulation in glomeruli is a hallmark of the disease, leading to nodular sclerosis and glomerulosclerosis eventually. Multiple molecular mechanisms involving abnormal metabolism of nutrients, oxidative stress, inflammation, and hyperactivity of the renin-angiotensin system contribute to glomerular pathophysiological changes and renal function deterioration in diabetes mellitus. This review focuses on disturbances in nutrient metabolism and their roles in the pathophysiology of glomerular impairments. Blood glucose control, cardiovascular risk factors intervention, blood pressure management, and renin-angiotensin system blockade are pivotal in preventing the development and progression of DKD. Future research is urgently needed to identify innovative therapeutic targets based on advances in molecular mechanisms.