How to monitor and manage the risk of Acute Kidney Injury (AKI) in patients on Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, based on estimated Glomerular Filtration Rate (eGFR) or creatinine levels?

Monitoring and Managing AKI Risk with SGLT2 Inhibitors Based on eGFR and Creatinine

When monitoring patients on SGLT2 inhibitors, an initial reversible decrease in eGFR of 3-5 mL/min/1.73 m² is expected and generally not a reason to discontinue therapy, unless the decline exceeds 30% from baseline or there are signs of volume depletion. 1

Initial Assessment Before Starting SGLT2i

• Evaluate baseline kidney function with eGFR and albuminuria measurements 1
• SGLT2 inhibitors are recommended for patients with eGFR ≥20 mL/min/1.73 m² 1
• Assess volume status and risk for volume depletion 1
• Consider reducing diuretic doses in patients at risk for hypovolemia before starting SGLT2i 1
• Review concurrent medications that may increase AKI risk (NSAIDs, nephrotoxic agents) 1

Monitoring Protocol After SGLT2i Initiation

First 4 Weeks

• Anticipate an acute drop in eGFR of 3-5 mL/min/1.73 m² which is hemodynamic and generally reversible 1
• Monitor serum creatinine within 2-4 weeks after initiation 1
• Assess for signs of volume depletion (orthostatic hypotension, dizziness) 2, 3

Ongoing Monitoring

• Continue routine monitoring of kidney function based on CKD stage 1
• For eGFR ≥60 mL/min/1.73 m²: Check every 6-12 months 1
• For eGFR 30-59 mL/min/1.73 m²: Check every 3-6 months 1
• For eGFR <30 mL/min/1.73 m²: Check every 1-3 months 1
• Monitor serum potassium levels in patients on concurrent RAS inhibitors or MRAs 1

Management of eGFR Changes

Acceptable Changes

• Decreases in eGFR up to 30% from baseline are generally acceptable and not a reason to discontinue therapy 1
• After initial dip, eGFR typically stabilizes during ongoing SGLT2i therapy 1
• Once initiated, it is reasonable to continue SGLT2i even if eGFR falls below 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1

When to Take Action

• For eGFR decline >30% from baseline: 1
  1. Ensure patient is euvolemic (adjust diuretic dosage if needed)
  2. Discontinue nonessential nephrotoxic agents
  3. Evaluate for alternative etiologies of AKI
  4. Consider temporary withholding SGLT2i if severe AKI is suspected 2

Special Situations Requiring SGLT2i Interruption

• Temporarily withhold SGLT2i during: 1

  1. Prolonged fasting
  2. Surgery or procedures requiring >1 day hospitalization (withhold at least 2 days before)
  3. Critical medical illness
  4. Acute volume depletion events
  5. Severe acute illness with reduced oral intake

• Resume SGLT2i when: 1

  1. Patient is clinically stable
  2. Eating and drinking normally
  3. No longer at risk for volume depletion

Risk Factors for AKI with SGLT2i

• Concurrent diuretic use (especially loop diuretics) 1, 2
• History of prior AKI 1, 4
• Advanced age (>75 years) 1, 5
• Lower baseline eGFR (higher risk with eGFR <45 mL/min/1.73 m²) 6, 4
• Tenuous volume status 1, 2
• Concurrent use of nephrotoxic medications 1, 2

Patient Education

• Advise about symptoms of volume depletion and when to seek medical attention 1
• Instruct on "sick day protocol" - temporarily withhold SGLT2i during illness with reduced oral intake 1
• Educate about maintaining adequate hydration 1
• Inform about the expected initial drop in eGFR 1

Evidence on SGLT2i and AKI Risk

Despite initial concerns, recent evidence suggests SGLT2 inhibitors are not associated with increased AKI risk and may even be protective:

• Multiple studies show SGLT2i use is associated with lower rates of AKI compared to other glucose-lowering drugs 7, 8, 5
• The initial FDA warnings about increased AKI risk have not been substantiated by subsequent research 7, 8
• The protective effect may be due to reduced intraglomerular pressure and improved tubuloglomerular feedback 1

Common Pitfalls to Avoid

• Discontinuing SGLT2i prematurely due to expected initial eGFR decline 1
• Failing to reduce diuretic doses in volume-depleted patients 1
• Not withholding SGLT2i during acute illness or perioperative periods 1
• Overlooking the need for more frequent monitoring in patients with lower baseline eGFR 1, 6
• Misinterpreting the initial eGFR decline as evidence of nephrotoxicity 1