What are the considerations for using Jardiance (Empagliflozin) in patients with Chronic Kidney Disease (CKD) stage 4 and Impaired Renal Function?

Jardiance (Empagliflozin) in CKD Stage 4

Jardiance (empagliflozin) is contraindicated in patients with CKD stage 4 (eGFR <30 mL/min/1.73 m²) and should not be initiated in patients with eGFR <45 mL/min/1.73 m².1

FDA Recommendations and Contraindications

• Empagliflozin should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m² 1
• The medication should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m² 1
• Severe renal impairment, end-stage renal disease, or dialysis are absolute contraindications for Jardiance 1

Risks in Advanced CKD

• Empagliflozin causes intravascular volume contraction which can lead to acute kidney injury, particularly in patients with pre-existing renal insufficiency 1
• Patients with CKD stage 4 are at higher risk for:
  • Acute kidney injury requiring hospitalization and potentially dialysis 1
  • Hypotension due to volume depletion 1
  • Reduced medication clearance 1

Monitoring Recommendations for CKD Patients

• Renal function should be evaluated prior to initiation of empagliflozin and monitored periodically thereafter 1
• More frequent renal function monitoring is recommended in patients with an eGFR below 60 mL/min/1.73 m² 1
• Patients with CKD stage 4 should be referred to a nephrologist for specialized management 2

Alternative Medications for Diabetes in CKD Stage 4

For patients with diabetes and CKD stage 4, alternative medications with better safety profiles include:

• Glipizide (preferred sulfonylurea as it does not have active metabolites) 2
• DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin) with appropriate dose adjustments 2
• Insulin with careful dose adjustment due to reduced renal clearance 2

Evidence from Recent Clinical Trials

While the FDA label contraindicates Jardiance in severe renal impairment, it's worth noting that newer research is exploring SGLT2 inhibitors in advanced CKD:

• The EMPA-KIDNEY trial (2023) included patients with eGFR as low as 20 mL/min/1.73 m² and showed empagliflozin reduced the risk of kidney disease progression 3
• The DAPA-CKD trial (2021) demonstrated that dapagliflozin (another SGLT2 inhibitor) had consistent benefits in stage 4 CKD patients with no evidence of increased risks 4

However, despite these promising research findings, current FDA labeling and guidelines still restrict empagliflozin use in advanced CKD.

Management Considerations for CKD Stage 4

• Referral to a nephrologist is recommended when CKD stage 4 develops (eGFR <30 mL/min/1.73 m²) 2
• Consultation with a nephrologist has been found to reduce cost, improve quality of care, and delay dialysis 2
• Blood pressure control with appropriate agents (ACE inhibitors, ARBs, CCBs, or thiazide diuretics) remains important 2
• Careful monitoring of electrolytes, metabolic acidosis, and calcium/phosphorus levels is essential 2

Conclusion

Based on current FDA labeling and guidelines, Jardiance is contraindicated in CKD stage 4 and should not be initiated when eGFR is below 45 mL/min/1.73 m². While emerging research suggests potential benefits of SGLT2 inhibitors in advanced CKD, clinical practice should adhere to current regulatory guidance until official labeling changes occur.