Residual Renal Risk in Diabetic Nephropathy Despite Contemporary Therapies

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and kidney failure worldwide.
• Despite advancements in RAAS inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, and mineralocorticoid receptor antagonists, a significant residual renal risk persists in DKD patients.
• This review addresses the ongoing challenges in managing DKD and the unmet needs in preventing renal decline.

Purpose of the Study:

• To synthesize current evidence on residual renal risk in diabetic kidney disease (DKD).
• To explore the underlying mechanisms contributing to persistent renal injury.
• To identify high-risk clinical phenotypes and therapeutic gaps in DKD management.

Main Methods:

• A comprehensive narrative review of existing literature was conducted.
• Included studies encompassed clinical trials, post hoc analyses, observational studies, and mechanistic research related to DKD.
• Literature search focused on residual renal risk, mechanisms of injury, and therapeutic strategies.

Main Results:

• Persistent inflammation, fibrosis, tubulointerstitial injury, and metabolic memory are central to residual renal risk in DKD.
• These factors contribute to progressive kidney damage despite current treatments.
• High-risk phenotypes like non-albuminuric DKD, rapid progressors, and late presenters with comorbidities exhibit a greater burden of these pathologies.

Conclusions:

• Residual risk factors in DKD present opportunities for improved clinical management and intervention.
• Further research is essential to refine therapeutic approaches for early intervention in DKD.
• Developing targeted therapies for inflammation, fibrosis, and metabolic dysfunction in the kidney is crucial for better outcomes and reduced kidney function loss.