What are the primary treatment recommendations for a patient with diabetic kidney disease?

Primary Treatment Recommendations for Diabetic Kidney Disease

For patients with diabetic kidney disease, immediately initiate an SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²) combined with metformin (if eGFR ≥30 mL/min/1.73 m²), add an ACE inhibitor or ARB if hypertension and albuminuria are present, and start statin therapy—this multi-drug approach forms the foundation of treatment regardless of current glycemic control. 1, 2

First-Line Pharmacologic Therapy

SGLT2 Inhibitors (Highest Priority)

• Start an SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m², even if glucose control is adequate, as kidney and cardiovascular protection occur independent of glucose-lowering effects 1, 2
• Continue SGLT2 inhibitors until dialysis or transplantation is initiated, even as eGFR declines below 30 mL/min/1.73 m² 1, 2
• SGLT2 inhibitors reduce heart failure hospitalizations and slow CKD progression through anti-inflammatory and anti-fibrotic mechanisms 3

Metformin

• Initiate metformin when eGFR ≥30 mL/min/1.73 m² at standard doses 1
• Reduce metformin dose to maximum 1000 mg daily when eGFR is 30-44 mL/min/1.73 m² 1, 2
• Discontinue metformin when eGFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk 1, 2

RAS Blockade (ACE Inhibitors or ARBs)

• Initiate an ACE inhibitor or ARB in all patients with diabetes, hypertension, AND albuminuria 1
• Titrate to the highest approved dose that is tolerated (e.g., lisinopril 40 mg daily, losartan 100 mg daily, telmisartan 80 mg daily) 1
• For patients with albuminuria but normal blood pressure, ACE inhibitor or ARB may still be considered 1
• Do NOT use ACE inhibitors or ARBs for primary prevention in patients with normal blood pressure and no albuminuria 1

Glycemic Monitoring and Targets

HbA1c Monitoring

• Use HbA1c to monitor glycemic control, checking every 3 months when therapy changes or targets are not met 1, 2
• Check at least twice yearly in stable patients 2
• Consider continuous glucose monitoring when HbA1c is discordant with clinical symptoms or blood glucose readings 1

Individualized HbA1c Targets

• Target HbA1c between <6.5% and <8.0% based on hypoglycemia risk, life expectancy, comorbidities, and patient preferences 1, 2
• Aim for <6.5% in younger patients with long life expectancy, no cardiovascular disease, and low hypoglycemia risk 1
• Aim for <8.0% in older patients with limited life expectancy, advanced complications, or high hypoglycemia risk 1

Additional Risk-Based Therapies

GLP-1 Receptor Agonists

• Add a long-acting GLP-1 RA (e.g., semaglutide, dulaglutide) if glycemic targets are not met with metformin and SGLT2 inhibitors, or if these agents cannot be used 1, 2
• GLP-1 RAs provide additional cardiovascular protection and promote weight loss 1

Nonsteroidal Mineralocorticoid Receptor Antagonist

• Add finerenone for patients with type 2 diabetes who have persistent albuminuria ≥30 mg/g despite first-line therapy and normal potassium levels 1, 2
• Finerenone reduces cardiovascular events and slows CKD progression through anti-inflammatory and anti-fibrotic effects 3

Statin Therapy

• Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) in all patients with diabetes and CKD, regardless of baseline LDL cholesterol 1, 2

Critical Monitoring and Safety

ACE Inhibitor/ARB Monitoring

• Monitor serum creatinine and potassium within 2-4 weeks after starting or increasing ACE inhibitor/ARB dose 1, 2, 4
• Continue therapy unless creatinine rises >30% within 4 weeks—this degree of increase warrants evaluation for acute kidney injury, volume depletion, or renal artery stenosis 1, 2
• Do not immediately discontinue ACE inhibitors/ARBs for hyperkalemia—first attempt dietary modification, diuretics, sodium bicarbonate, or GI cation exchangers 1, 2

Hypoglycemia Prevention

• Reduce insulin or sulfonylurea doses when starting SGLT2 inhibitors to prevent hypoglycemia 2
• Educate patients on hypoglycemia symptoms, which may be blunted in CKD 5

Lifestyle Interventions

Dietary Modifications

• Limit protein intake to 0.8 g/kg/day for patients not on dialysis 1, 2
• Restrict sodium intake to <2 g/day (<90 mmol/day or <5 g sodium chloride/day) 1, 2
• Consume a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts; lower in processed meats, refined carbohydrates, and sweetened beverages 1

Physical Activity

• Advise moderate-intensity physical activity for at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance 1, 2

Tobacco Cessation

• Strongly recommend tobacco cessation for all patients who use tobacco products 1, 2

Common Pitfalls to Avoid

• Do not withhold SGLT2 inhibitors based solely on HbA1c levels—their benefits extend beyond glucose control 1, 2
• Do not combine ACE inhibitors and ARBs—this increases adverse events without additional benefit 1
• Do not restrict protein below 0.8 g/kg/day—lower intake does not improve outcomes and may cause malnutrition 1
• Do not delay referral to nephrology when eGFR <30 mL/min/1.73 m² or uncertainty exists about etiology 1