Guideline-Directed Medical Therapy for Diabetic Kidney Disease: Advances in Primary and Secondary Prevention

Figures

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  Figure 1. Flow diagram illustrating the literature identification and study selection process for this narrative review.

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  Figure 2. Pathophysiological cascade of diabetic kidney disease (DKD). Chronic hyperglycemia initiates a series of metabolic and hemodynamic alterations—including the formation of advanced glycation end products (AGEs), increased oxidative stress, activation of protein kinase C (PKC), and intraglomerular hypertension through renin-angiotensin-aldosterone system (RAAS) activation. These processes collectively lead to glomerular injury characterized by mesangial expansion, thickening of the glomerular basement membrane (GBM), and podocyte loss. Progressive glomerular damage increases permeability, resulting in proteinuria—especially albuminuria—which subsequently drives tubulointerstitial inflammation, fibrosis, and ultimately progression to end-stage kidney disease (ESKD). Image credit: Susant Katwal

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  Figure 3. Primary prevention framework for diabetic kidney disease (DKD). The figure illustrates a stepwise approach to the primary prevention of DKD beginning at the stage of diabetes diagnosis. Immediate actions include baseline screening of urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), alongside implementation of lifestyle modifications, such as dietary optimization, regular exercise, and smoking cessation. Ongoing management focuses on maintaining glycemic and blood pressure control and periodic monitoring of renal function. Annual UACR/eGFR assessments and medication reviews are recommended for all patients, with quarterly monitoring and early initiation of sodium-glucose co-transporter 2 (SGLT2) inhibitors for high-risk individuals. The primary prevention targets include achieving HbA1c <7%, blood pressure <130/80 mmHg, and UACR <30 mg/g to prevent or delay the onset of DKD. Image Credit: Shweta Menon

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  Figure 4. Secondary prevention and guideline-directed medical therapy for diabetic kidney disease (DKD). The figure outlines a comprehensive framework for secondary prevention in patients with established DKD, emphasizing evidence-based pharmacologic interventions. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are recommended for initiation when estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m² and continued until dialysis or transplant. Metformin may be used when eGFR ≥30 mL/min/1.73 m². Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and other glucose-lowering agents can be added to achieve individualized glycemic targets or when persistent albuminuria exists. For blood pressure control, renin-angiotensin system (RAS) inhibitors at the maximum tolerated dose form the cornerstone, with dihydropyridine calcium channel blockers (CCBs), diuretics, and mineralocorticoid receptor antagonists (MRAs) added as needed for resistant hypertension. Lipid management includes moderate- or high-intensity statins, with adjunctive therapies such as ezetimibe, PCSK9 inhibitors, or icosapent ethyl based on atherosclerotic cardiovascular disease (ASCVD) risk and lipid profile.…