What are the considerations for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as dapagliflozin, in an 85-year-old patient with Chronic Kidney Disease (CKD) stage 4 and impaired renal function?

SGLT2 Inhibitor Use in an 85-Year-Old with CKD Stage 4

SGLT2 inhibitors, specifically dapagliflozin, can be used in an 85-year-old patient with CKD stage 4 for kidney and cardiovascular protection, with initiation recommended at eGFR ≥20 mL/min/1.73 m² despite reduced glycemic efficacy at this level of kidney function. 1

Efficacy Considerations in Advanced CKD

• SGLT2 inhibitors provide significant benefits in CKD stage 4 patients:

  • Slow eGFR decline (difference of 1.23 mL/min/1.73 m² per year slower decline with dapagliflozin vs. placebo) 2
  • Reduce risk of kidney failure progression by approximately 27% 2
  • Decrease cardiovascular events and mortality 1

• Benefits persist despite reduced glycemic efficacy:

  • While glucose-lowering effects diminish at lower eGFR levels, kidney and cardiovascular protective effects remain 1
  • The KDOQI Work Group strongly recommends SGLT2 inhibitors for patients with eGFR ≥20 mL/min/1.73 m² 1

Medication Selection and Dosing

For an 85-year-old with CKD stage 4:

1. Dapagliflozin is preferred based on evidence:

   • FDA approved for use down to eGFR 20 mL/min/1.73 m² 3
   • 10 mg daily is the recommended dose for kidney protection 1
   • May continue until dialysis initiation if well tolerated 1

2. Alternative options if dapagliflozin is not suitable:

   • Canagliflozin: Maximum 100 mg daily (not recommended for initiation at this eGFR level but may continue if already tolerating) 1
   • Empagliflozin: Not recommended for initiation at eGFR <45 mL/min/1.73 m² 1

Safety Considerations for Elderly CKD Patients

1. Volume depletion risk:

   • Assess volume status before initiation 3
   • Consider reducing diuretic dose in patients at risk for hypovolemia 1
   • Monitor for signs of hypotension, especially in elderly patients 3

2. Initial eGFR dip:

   • Expect a reversible decline in eGFR of 3-5 mL/min/1.73 m² in the first 4 weeks 1
   • This is hemodynamic in nature and not a reason to discontinue therapy 1

3. Infection risk:

   • Higher risk of genital mycotic infections 3
   • Implement daily hygiene to keep genital area clean and dry 1
   • Monitor for urinary tract infections 3

4. Sick day management:

   • Hold SGLT2 inhibitors during acute illness with nausea, vomiting, or diarrhea 1
   • Implement "STOP DKA" protocol if needed (stop SGLT2 inhibitor, test for ketones, maintain fluid and carbohydrate intake) 1

Monitoring Recommendations

1. Before initiation:

   • Assess baseline renal function and volume status 3
   • Review concurrent medications, especially diuretics 1

2. After initiation:

   • Monitor renal function at 2-4 weeks to assess initial eGFR dip 1
   • Regular follow-up of renal parameters every 3-6 months 1
   • Assess for signs of volume depletion or hypotension 3
   • Monitor for genital and urinary tract infections 1

Special Considerations for the 85-Year-Old Patient

1. Fall risk:

   • Volume depletion and hypotension may increase fall risk in elderly patients 3
   • Start at lowest dose and titrate slowly 1
   • Consider reducing concurrent diuretic dose 1

2. Polypharmacy:

   • SGLT2 inhibitors can facilitate use of other kidney-protective medications:
     • Reduce risk of hyperkalemia (facilitating RAS inhibitor use) 1
     • Mitigate fluid retention (facilitating use of other heart failure medications) 1

3. Cognitive function:

   • Ensure patient or caregiver understands medication instructions and sick day rules 1
   • Provide clear written instructions about when to hold medication

Common Pitfalls to Avoid

1. Therapeutic nihilism:

   • Despite advanced age and CKD stage, evidence supports SGLT2 inhibitor benefits 1, 2
   • Do not withhold therapy solely based on age or CKD stage when eGFR remains ≥20 mL/min/1.73 m² 1

2. Misinterpreting initial eGFR decline:

   • The initial 3-5 mL/min/1.73 m² drop is expected and not a reason to discontinue 1
   • Long-term kidney protection occurs despite this initial dip 1

3. Inadequate patient education:

   • Failure to counsel on sick day management increases DKA risk 1
   • Inadequate hygiene instructions increases infection risk 1

4. Continuing at dialysis initiation:

   • While FDA has removed the requirement to discontinue dapagliflozin at dialysis initiation, efficacy in dialysis patients remains unproven 1
   • Monitor closely if continuing therapy after dialysis initiation

In conclusion, SGLT2 inhibitors, particularly dapagliflozin, offer significant kidney and cardiovascular protection for elderly patients with CKD stage 4, with benefits outweighing risks when appropriate monitoring and precautions are implemented.