What is the recommended management for a patient with Chronic Kidney Disease (CKD) and Diabetes Mellitus (DM)?

Management of Chronic Kidney Disease and Diabetes Mellitus

Patients with diabetes and CKD require a comprehensive, multi-drug strategy centered on SGLT2 inhibitors and metformin as first-line therapy (when eGFR ≥30 ml/min/1.73 m²), combined with RAS blockade for those with albuminuria and hypertension, statin therapy for all patients, and lifestyle modifications including dietary changes and exercise. 1, 2

Pharmacologic Management Algorithm for Type 2 Diabetes

First-Line Therapy (eGFR ≥30 ml/min/1.73 m²)

Start both medications simultaneously: 1, 2

• Metformin: Initiate at 500 mg twice daily or 850 mg once daily with meals, titrating up to maximum 2550 mg/day in divided doses based on tolerance 3

  • Reduce dose when eGFR falls below 45 ml/min/1.73 m² 3
  • Discontinue when eGFR falls below 30 ml/min/1.73 m² 3
  • Monitor for lactic acidosis risk, especially in elderly patients and those with hepatic impairment 3

• SGLT2 inhibitor: Initiate when eGFR ≥20 ml/min/1.73 m² and continue until dialysis or transplantation 1, 2

  • This provides cardiovascular and kidney protection independent of glucose-lowering effects 1, 4
  • The initial reversible eGFR decrease after initiation is not a reason to discontinue 2

Second-Line Therapy (If Glycemic Targets Not Met)

• Long-acting GLP-1 receptor agonist: Add if HbA1c targets not achieved with metformin and SGLT2i, or if these medications cannot be used 1, 2
  • Preferred due to cardiovascular benefits and low hypoglycemia risk 1, 4
  • Particularly beneficial in patients with established atherosclerotic cardiovascular disease 1

Additional Risk-Based Therapy

• Nonsteroidal mineralocorticoid receptor antagonist (finerenone): Add for patients with T2D, eGFR ≥25 ml/min/1.73 m², normal serum potassium, and persistent albuminuria (ACR ≥30 mg/g or ≥3 mg/mmol) 1, 2

• Insulin: Use when eGFR <30 ml/min/1.73 m² or on dialysis, or when other agents are insufficient 1

Blood Pressure Management

Initiate ACE inhibitor or ARB for all patients with diabetes, hypertension, AND albuminuria: 1, 2

• Titrate to the highest approved dose tolerated 1, 2
• Monitor serum creatinine, potassium, and blood pressure within 2-4 weeks of initiation or dose increase 1
• Continue therapy even when eGFR falls below 30 ml/min/1.73 m² unless specific contraindications arise 2
• Discontinue only if serum creatinine rises by more than 30% or hyperkalemia develops 1

For patients without albuminuria: Consider dihydropyridine calcium channel blocker or diuretic as first-line agents 1

Lipid Management

All patients with diabetes and CKD require statin therapy: 1, 2

• Moderate-intensity statin for primary prevention of atherosclerotic cardiovascular disease 2
• High-intensity statin for patients with known ASCVD or multiple risk factors 2
• Add ezetimibe, PCSK9 inhibitor, or icosapent ethyl based on ASCVD risk and lipid levels 1

Glycemic Targets and Monitoring

Target HbA1c between 6.5% and 8.0% based on individual patient factors: 1, 2

• Lower targets (<6.5% or <7.0%) are appropriate for patients at low hypoglycemia risk using agents that don't cause hypoglycemia 1
• Higher targets (closer to 8.0%) for patients with limited life expectancy, high hypoglycemia risk, or extensive comorbidities 1

Monitoring approach: 2, 5

• HbA1c remains the primary monitoring tool but becomes less reliable as eGFR declines 2, 4
• Consider continuous glucose monitoring when HbA1c is unreliable due to advanced CKD or when there is discordance between HbA1c and clinical symptoms 1, 2, 4, 5
• CGM metrics (time in range, time in hypoglycemia) can serve as alternatives to HbA1c in some patients 1

Lifestyle Interventions

Dietary Recommendations

Prescribe a specific dietary pattern: 1, 2

• High in: vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts 1, 2
• Low in: processed meats, refined carbohydrates, and sweetened beverages 1, 2

Protein intake: 1, 2

• 0.8 g/kg/day for patients NOT on dialysis 1, 2
• 1.0-1.2 g/kg/day for patients on hemodialysis or peritoneal dialysis 1, 2

Sodium restriction: 1, 2

• <2 g sodium per day (<90 mmol/day or <5 g sodium chloride/day) 1, 2

Physical Activity

Prescribe at least 150 minutes per week of moderate-intensity physical activity: 1, 2

• Adjust intensity based on cardiovascular tolerance and physical limitations 1, 2
• Counsel patients to avoid sedentary behavior 1, 2
• For patients at high fall risk, provide specific guidance on exercise type (aerobic vs. resistance) and intensity 1

Weight Management

Encourage weight loss for patients with obesity, particularly when eGFR ≥30 ml/min/1.73 m²: 1, 2, 4

Smoking Cessation

All patients who use tobacco must be counseled on smoking cessation: 1, 2

Monitoring Schedule

Kidney function monitoring frequency: 2, 4

• Annually when eGFR ≥60 ml/min/1.73 m² 2
• Every 3-6 months when eGFR <60 ml/min/1.73 m² 2
• More frequently in elderly patients at risk for renal impairment 3

Annual screening requirements: 2

• Spot urine albumin-to-creatinine ratio 2
• eGFR calculation 2
• Vitamin B12 levels (every 2-3 years in patients on metformin) 3

Critical Pitfalls to Avoid

Metformin-related errors: 3

• Never initiate metformin when eGFR is between 30-45 ml/min/1.73 m² 3
• Discontinue metformin before iodinated contrast procedures in patients with eGFR 30-60 ml/min/1.73 m², history of liver disease, alcoholism, heart failure, or intra-arterial contrast administration 3
• Re-evaluate eGFR 48 hours after contrast before restarting 3

RAS blockade errors: 1

• Do not discontinue ACE inhibitor or ARB prematurely when eGFR declines unless creatinine rises >30% or severe hyperkalemia develops 1
• Avoid dual RAS blockade (ACE inhibitor + ARB) 1

Hypoglycemia risk: 3

• Reduce insulin or sulfonylurea doses when adding metformin to minimize hypoglycemia risk 3
• First-generation sulfonylureas should be avoided in CKD stage 3b; prefer glipizide or gliclazide if sulfonylurea is needed 4

Type 1 Diabetes Considerations

Insulin remains the cornerstone of therapy for type 1 diabetes: 1

• Defer to existing diabetes organization guidelines for insulin management 1
• Apply the same comprehensive strategy for cardiovascular and kidney protection (RAS blockade, statins, lifestyle modifications) 1
• SGLT2 inhibitors are not first-line for type 1 diabetes but may be considered in select cases 1