What is the treatment approach for patients with Diabetes Mellitus (DM) who also have Chronic Kidney Disease (CKD) or End-Stage Renal Disease (ESRD)?

Treatment Approach for Diabetes Mellitus in CKD and ESRD

For patients with diabetes mellitus and chronic kidney disease (CKD) or end-stage renal disease (ESRD), treatment should follow a comprehensive strategy with SGLT2 inhibitors as first-line therapy for type 2 diabetes with CKD, and metformin when eGFR ≥30 ml/min/1.73 m², along with RAS blockade for those with albuminuria and hypertension.

Comprehensive Management Strategy

The management of diabetes in patients with CKD requires a multi-layered approach targeting several risk factors:

First-Line Medications Based on CKD Stage:

For Type 2 Diabetes:

• eGFR ≥30 ml/min/1.73 m²:

  • Metformin (start with 1000 mg daily in eGFR 30-44 ml/min/1.73 m²) 1
  • SGLT2 inhibitor (can be initiated when eGFR ≥20 ml/min/1.73 m²) 1

• eGFR 20-29 ml/min/1.73 m²:

  • SGLT2 inhibitor (continue if already started) 1
  • GLP-1 receptor agonist 1

• eGFR <20 ml/min/1.73 m² or dialysis:

  • GLP-1 receptor agonist
  • Insulin
  • DPP-4 inhibitors (can be used in ESRD) 1, 2

For Type 1 Diabetes:

• Insulin therapy across all CKD stages 1

Cardiovascular and Renal Protection:

• RAS blockade: ACE inhibitor or ARB for patients with albuminuria and hypertension, titrated to maximum tolerated dose 1
• Statin therapy: Recommended for all patients with diabetes and CKD 1
• Nonsteroidal mineralocorticoid receptor antagonist (ns-MRA): For patients with T2D, eGFR ≥25 ml/min/1.73 m², normal potassium, and albuminuria 1

Medication-Specific Considerations

SGLT2 Inhibitors

• Provide significant cardiovascular and renal protection 3
• Can be initiated at eGFR ≥20 ml/min/1.73 m² and continued until dialysis or transplantation 1
• Reduce risk of MACE (Major Adverse Cardiovascular Events) with hazard ratio of 0.86 3

Metformin

• Safe and effective when eGFR ≥30 ml/min/1.73 m² 1
• Requires dose adjustment with declining kidney function 1
• Monitor eGFR more frequently when <60 ml/min/1.73 m² 1
• Neutral effects on MACE and all-cause mortality in CKD stages 3-4 4

GLP-1 Receptor Agonists

• Preferred additional agent when glycemic targets not met with metformin and SGLT2i 1
• Can be used across most CKD stages including advanced CKD 1

Insulin

• Main therapy for T1D across all CKD stages
• Often needed in advanced CKD/ESRD with T2D
• Requires dose adjustments as kidney function declines due to decreased insulin clearance

Lifestyle Management

• Dietary protein: 0.8 g/kg body weight per day for non-dialysis CKD; higher (1.0-1.2 g/kg) for dialysis patients 1
• Sodium restriction: <2 g/day (<5 g sodium chloride) 1
• Physical activity: At least 150 minutes per week of moderate-intensity activity 1
• Weight management: Encourage weight loss for obese patients with eGFR ≥30 ml/min/1.73 m² 1

Monitoring Considerations

• Glycemic monitoring: Consider continuous glucose monitoring in ESRD patients on dialysis due to limitations of HbA1c 5
• Kidney function: Regular monitoring of eGFR and albuminuria
• Screen for CKD: Annually from diagnosis in T2D; 5 years after diagnosis in T1D 1

Common Pitfalls to Avoid

1. Don't discontinue RAS blockade for minor increases in serum creatinine (≤30%) in the absence of volume depletion 1

2. Don't withhold metformin in patients with eGFR ≥30 ml/min/1.73 m² due to unfounded fears of lactic acidosis 6, 7

3. Don't rely solely on HbA1c for glycemic monitoring in advanced CKD and ESRD due to altered red blood cell lifespan

4. Don't delay nephrology referral for patients with eGFR <30 ml/min/1.73 m² or rapidly declining kidney function 1

5. Don't overlook the importance of comprehensive care including blood pressure control, lipid management, and lifestyle modifications 1

By following this evidence-based approach to diabetes management in CKD and ESRD, clinicians can significantly reduce the risk of disease progression and cardiovascular complications while improving patient outcomes.