Can I use Invokana (canagliflozin) in patients with stage 4 kidney disease (Impaired renal function)?

Use of Invokana (Canagliflozin) in Stage 4 Kidney Disease

Invokana (canagliflozin) should not be initiated in patients with stage 4 kidney disease (eGFR <30 mL/min/1.73 m²), but patients already taking it for albuminuria >300 mg/day may continue at 100 mg daily to reduce the risk of kidney disease progression and cardiovascular events. 1, 2

Recommendations Based on Kidney Function

Stage 4 CKD (eGFR 15-29 mL/min/1.73 m²):

• Initiation: Not recommended for new patients 1, 2
• Continuation: May continue 100 mg daily if already taking it with albuminuria >300 mg/day for kidney and cardiovascular benefits until dialysis 1
• Glycemic efficacy: Significantly reduced at this level of kidney function 1

Important considerations:

1. FDA labeling: The FDA label specifically states that initiation is not recommended with eGFR <30 mL/min/1.73 m², but patients with albuminuria >300 mg/day may continue at 100 mg once daily 2

2. Benefits in continuing therapy:

   • Reduces risk of end-stage kidney disease (ESKD)
   • Reduces risk of doubling of serum creatinine
   • Reduces cardiovascular death
   • Reduces hospitalization for heart failure 1, 2

Evidence Supporting This Recommendation

The 2022 American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report explicitly states that while initiation is not recommended in stage 4 CKD, patients may continue canagliflozin 100 mg daily if tolerated for kidney and cardiovascular benefit until dialysis 1.

The CREDENCE trial demonstrated that canagliflozin reduced the risk of kidney composite outcomes by 30% in patients with type 2 diabetes and diabetic nephropathy with albuminuria >300 mg/day 1, 3. Importantly, these benefits were consistent across different baseline eGFR levels, including those with lower eGFR 3.

Safety Considerations

Potential adverse effects to monitor:

• Acute kidney injury: Risk appears lower with canagliflozin compared to placebo in patients with CKD (HR 0.85) 3
• Volume depletion: Higher risk in patients with impaired renal function 1
• Euglycemic ketoacidosis: Monitor for this rare but serious complication, especially in insulin-dependent patients 1
• Genital mycotic infections: More common with SGLT2 inhibitors (6% vs 1% with placebo) 1

Monitoring recommendations:

• Assess renal function before initiating and periodically thereafter
• Monitor for signs of volume depletion
• Consider temporary discontinuation during acute illness or prolonged fasting
• Expect an initial small decrease in eGFR that typically stabilizes over time 3

Clinical Approach

1. For patients not currently on canagliflozin with stage 4 CKD:

   • Do not initiate canagliflozin
   • Consider other diabetes medications appropriate for CKD stage 4

2. For patients already on canagliflozin with stage 4 CKD:

   • If albuminuria >300 mg/day: Continue canagliflozin 100 mg daily
   • Monitor renal function regularly
   • Be vigilant for adverse effects
   • Continue until dialysis initiation

3. For patients approaching stage 4 CKD on canagliflozin:

   • Do not discontinue solely based on eGFR decline to <30 mL/min/1.73 m²
   • Continue to monitor closely
   • Maintain at 100 mg daily (do not use 300 mg dose)

Conclusion

The evidence strongly supports that while canagliflozin should not be initiated in stage 4 CKD, continuing it in patients already taking the medication with significant albuminuria provides important kidney and cardiovascular benefits that outweigh potential risks.