Management of Jardiance (Empagliflozin) in Acute Kidney Injury
Jardiance (empagliflozin) should be temporarily discontinued in any setting of acute kidney injury until renal function has returned to baseline or stabilized. 1
Mechanism and Concerns
SGLT2 inhibitors like Jardiance work through several mechanisms that can potentially worsen an existing AKI:
- Volume depletion effects: Jardiance causes intravascular volume contraction through its diuretic and natriuretic effects 1
- Hemodynamic changes: SGLT2 inhibitors typically cause an initial "eGFR dip" of 3-5 mL/min/1.73 m² within the first 4 weeks of therapy 2
- Risk factors: The FDA label specifically warns that factors predisposing patients to acute kidney injury include hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs) 1
Evidence Supporting Discontinuation
The FDA label for Jardiance explicitly states:
"Consider temporarily discontinuing JARDIANCE in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue JARDIANCE promptly and institute treatment." 1
This recommendation aligns with the broader concept of "sick day protocols" recommended by KDOQI guidelines, which advise holding SGLT2 inhibitors during acute illness, particularly when accompanied by volume depletion 2.
Potential Complications
Several case reports highlight serious complications when SGLT2 inhibitors are continued during AKI:
- Osmotic nephrosis requiring dialysis 3
- Acute interstitial nephritis 4, 5
- Exacerbation of AKI in patients with concomitant RAAS blockers 6
Management Algorithm
- Immediate action: Discontinue Jardiance when AKI is diagnosed
- Monitoring:
- Evaluate renal function daily during the acute phase
- Monitor for signs of metabolic acidosis and ketoacidosis, which can occur with SGLT2 inhibitors even with normal blood glucose levels 1
- Supportive care:
- Provide appropriate volume resuscitation if hypovolemia is present
- Discontinue other potentially nephrotoxic medications
- Restarting considerations:
- Wait until renal function has returned to baseline or stabilized
- Ensure adequate volume status before restarting
- Consider starting at a lower dose than previously used
- Monitor renal function within 2-4 weeks after restarting 2
Additional Considerations
- Concomitant medications: Particular caution is needed when patients are also on RAAS inhibitors (ACE inhibitors, ARBs) or diuretics, as these combinations increase AKI risk 2, 6
- Underlying conditions: Patients with heart failure or chronic kidney disease require especially careful monitoring when restarting SGLT2 inhibitors after an AKI episode
- Ketoacidosis risk: Monitor for signs of ketoacidosis during acute illness, as SGLT2 inhibitors can precipitate this condition even with relatively normal blood glucose levels 1
Pitfalls to Avoid
- Delayed recognition: AKI may not be immediately apparent in patients on SGLT2 inhibitors due to their effects on creatinine clearance
- Premature restart: Restarting Jardiance before adequate recovery of renal function may lead to recurrent AKI
- Failure to monitor: After restarting, close monitoring of renal function is essential to detect any early signs of recurrent kidney injury
While some emerging research suggests potential protective effects of SGLT2 inhibitors against certain forms of AKI 7, the current consensus and FDA guidance clearly support temporary discontinuation during acute kidney injury episodes to prevent worsening kidney damage.