Relationship between glomerular hyperfiltration and diabetic nephropathy progression: pathophysiological mechanisms, clinical evidence, and therapeutic perspectives

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal disease globally, with glomerular hyperfiltration (GH) emerging as a critical early pathophysiological driver. This review synthesizes current evidence on the mechanisms linking GH to DN progression and evaluates therapeutic strategies to mitigate its effects. A systematic literature search (2020–2024) across PubMed, Scopus, and Web of Science identified 22 studies, including clinical trials, cohort analyses, and experimental models. GH arises from hyperglycemia-induced renal hemodynamic changes, including afferent arteriole vasodilation, impaired tubuloglomerular feedback, and renin-angiotensin-aldosterone system (RAAS) activation. Clinical evidence demonstrates that elevated glomerular filtration rate (GFR) correlates with accelerated renal decline, structural damage (e.g., glomerulosclerosis), and increased mortality in diabetic patients. Longitudinal studies highlight GH as a predictor of end-stage kidney disease, with hazard ratios exceeding 2.0 for adverse renal outcomes. Therapeutically, RAAS inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors show robust efficacy in reducing hyperfiltration, albuminuria, and disease progression. Emerging therapies, such as GLP-1 agonists, mineralocorticoid receptor antagonists, and Astragaloside IV, offer additional renoprotective benefits via anti-inflammatory and antifibrotic mechanisms. Non-pharmacological interventions, including intensive glycemic control and dietary protein restriction, further support renal preservation. Future directions emphasize personalized approaches using predictive models and combination therapies to optimize outcomes. In conclusion, early targeting of GH through multimodal strategies represents a pivotal opportunity to delay DN progression, underscoring the need for integrated clinical and technological advancements in diabetes care.