Should a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor be stopped in a patient with type 2 diabetes who develops acute kidney injury (AKI) from cellulitis?

SGLT2 Inhibitor Management in AKI from Cellulitis

Yes, SGLT2 inhibitors should be temporarily discontinued when a patient develops AKI from cellulitis and resumed only after complete recovery with stable kidney function and adequate volume status. 1

Rationale for Discontinuation

The KDIGO 2022 guidelines explicitly recommend withholding SGLT2 inhibitors during acute illness with fluid losses and critical medical illness when patients are at greater risk for ketosis. 1 Cellulitis causing AKI represents exactly this scenario—an acute infectious process that typically involves:

• Volume depletion from fever, reduced oral intake, and inflammatory fluid shifts 1
• Hemodynamic instability that can worsen kidney injury 1
• Risk of compounding prerenal azotemia with SGLT2 inhibitor-induced osmotic diuresis 2

The combination of AKI and SGLT2 inhibitor-induced volume depletion creates a dangerous synergy that can worsen kidney injury, particularly in hypovolemic patients who are more susceptible to further renal function deterioration. 1

Physiologic Mechanisms of Harm

SGLT2 inhibitors can precipitate or worsen AKI through multiple mechanisms during acute illness:

• Altered transglomerular filtration from volume contraction 2
• Potential kidney medullary hypoxia 2
• Osmotic nephropathy from proximal tubular glucose accumulation, which has been documented in case reports of severe AKI requiring dialysis 3, 4
• Synergistic nephrotoxicity when combined with RAS blockers (present in all seven AKI cases in one case series) 2

Volume depletion from cellulitis-related fever, poor oral intake, and third-spacing is particularly dangerous because it may trigger osmotic nephropathy, especially in patients with pre-existing renal dysfunction. 3

When to Resume SGLT2 Inhibitors

Restart SGLT2 inhibitors only when ALL of the following criteria are met: 1

• Patient is eating and drinking normally 1
• Complete resolution of the acute cellulitis and systemic illness 1
• Adequate volume status and hemodynamic stability confirmed 1
• Kidney function has stabilized or improved (not necessarily back to baseline, but stable) 1

The median onset time to AKI after SGLT2 inhibitor initiation is 72 days, but AKI can occur anywhere from 7 to 365 days after starting therapy. 5 Recovery typically occurs within 2 weeks of discontinuation. 3, 4

Long-Term Management After Recovery

Once successfully restarted following AKI recovery, SGLT2 inhibitors can be continued even if eGFR subsequently falls below 20 mL/min/1.73 m², unless kidney replacement therapy is initiated. 1 This is critical because the reversible eGFR dip seen with chronic SGLT2 inhibitor use in stable CKD is fundamentally different from acute illness-related AKI and should not prompt discontinuation. 1

Common Pitfalls to Avoid

Do not confuse the expected initial eGFR dip with AKI. 1 The KDIGO guidelines specifically warn against this error—the hemodynamic eGFR reduction seen when initiating SGLT2 inhibitors in stable patients (typically 3-5 mL/min/1.73 m²) is expected and not an indication to stop therapy. 6, 1

Do not continue SGLT2 inhibitors during acute illness "because they're kidney protective." 1 While SGLT2 inhibitors provide long-term renoprotection in stable CKD, this benefit does not apply during acute illness states where volume depletion and hemodynamic instability predominate.

Consider reducing concomitant diuretics before restarting if the patient was on loop or thiazide diuretics, as these compound volume depletion risk. 6, 1

Educate patients about "sick day protocols" to temporarily withhold SGLT2 inhibitors during future illnesses, maintain hydration, and seek medical attention early. 6, 1

Special Considerations for Cellulitis

Cellulitis presents unique risks beyond typical AKI scenarios:

• Ongoing infection may require continued antibiotics that could be nephrotoxic (e.g., vancomycin, aminoglycosides) 2
• Immunocompromised patients or those with foot ulcers may have relative contraindications to SGLT2 inhibitor resumption 6, 7
• Patients over 65 years have higher fatality rates from SGLT2 inhibitor-associated AKI (mean age of deceased patients 62.9 years vs. 57.8 years for survivors) 5

The hospitalization rate for SGLT2 inhibitor-associated AKI is 63.5%, underscoring the severity of these events. 5