Evolving strategies for nephroprotection in diabetic kidney disease: From established therapies to novel interventions

Abstract

The prevalence of diabetes mellitus is increasing worldwide, and diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. DKD is characterized by progressive albuminuria and decline in kidney function driven by chronic hyperglycemia, glomerular hypertension, inflammation, and structural renal damage. Traditionally, DKD management has relied on lifestyle modification, glycemic control, blood pressure reduction, and renin–angiotensin–aldosterone system inhibition, with clinical trials demonstrating delayed disease progression. Despite these measures, substantial residual renal risk persists. Recent randomized trials have established the nephroprotective role of newer therapies. Sodium–glucose co-transporter 2 inhibitors, including canagliflozin, dapagliflozin, and empagliflozin, reduce the risk of sustained kidney function decline, kidney failure, and renal or cardiovascular death. Glucagon-like peptide-1 receptor agonists such as liraglutide, semaglutide, and dulaglutide lower albuminuria and slow renal function loss. In addition, the non-steroidal mineralocorticoid receptor antagonist finerenone provides further renal and cardiovascular protection when added to renin–angiotensin system blockade in patients with albuminuric DKD. This review summarizes clinical trial evidence supporting established and emerging therapies for nephroprotection in DKD, highlighting the shift toward earlier and combined treatment strategies to improve long-term kidney outcomes in patients with diabetes.

Keywords: Diabetic kidney disease; Sodium-glucose co-transporter 2 inhibitors; Diabetic nephropathy; Diabetes mellitus; Albuminuria

Core Tip: Diabetic kidney disease (DKD) is a complex and leading cause of end-stage renal disease, traditionally managed through glycemic and blood pressure control. However, recent advances, including sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and mineralocorticoid receptor antagonists, offer renoprotective benefits beyond glucose lowering, marking a significant shift in DKD treatment strategies and providing new hope for improved kidney outcomes in diabetes care.