Should Jardiance (Empagliflozin) be stopped in a patient with impaired renal function after a significant increase in serum creatinine (Cr) level?

Jardiance Should Be Discontinued Due to Significant Creatinine Elevation

Jardiance (empagliflozin) should be discontinued immediately when serum creatinine rises from 1.7 to 2.31 mg/dL within one week of initiation, as this represents a 36% increase in creatinine which exceeds safety thresholds.

Assessment of Renal Function Decline

The FDA label for Jardiance (empagliflozin) provides clear guidance on renal function monitoring and discontinuation criteria:

• Jardiance should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m² 1
• Jardiance should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m² 1

The observed increase in creatinine from 1.7 to 2.31 mg/dL represents a 36% increase, which is significant and concerning for several reasons:

1. This exceeds the generally accepted safety threshold of a 30% increase in serum creatinine
2. The rapid timeframe (one week) suggests an acute kidney injury rather than expected hemodynamic changes
3. The baseline creatinine of 1.7 mg/dL already indicates impaired renal function

Clinical Decision Algorithm

Step 1: Assess the magnitude of creatinine elevation

• Calculate percent increase: (2.31-1.7)/1.7 × 100 = 36% increase
• This exceeds the 30% threshold that would warrant medication discontinuation 2

Step 2: Determine eGFR impact

• While exact eGFR values aren't provided, a creatinine of 2.31 mg/dL likely corresponds to an eGFR below 45 mL/min/1.73 m², especially in older adults
• Jardiance is contraindicated when eGFR falls below 45 mL/min/1.73 m² 1

Step 3: Take appropriate action

• Discontinue Jardiance immediately
• Investigate other potential causes of renal function decline
• Monitor renal function until stabilization occurs

Rationale for Discontinuation

The American Heart Association guidelines state that "a rise in serum creatinine >0.5 mg/dL if the initial serum creatinine is 2.0 mg/dL (or a rise >1.0 mg/dL if the baseline creatinine exceeds 2.0 mg/dL), particularly if the level progressively increases thereafter, should prompt consideration for stopping the medication" 2.

While these guidelines were originally developed for ACE inhibitors, the principle applies to SGLT2 inhibitors like Jardiance, which can also affect renal hemodynamics. The observed increase of 0.61 mg/dL from a baseline of 1.7 mg/dL (36% increase) exceeds the safety threshold.

Monitoring After Discontinuation

After discontinuing Jardiance:

• Recheck renal function within 3-7 days
• Evaluate for volume depletion and correct if present
• Assess for other nephrotoxic medications that may need adjustment
• Consider nephrology consultation if renal function doesn't improve

Important Considerations and Caveats

1. Distinguish from expected changes: While SGLT2 inhibitors can cause an initial modest decline in eGFR (typically <10%), a 36% increase in creatinine within one week is excessive and concerning 3, 4

2. Investigate other causes: Consider volume depletion, concurrent medications (especially NSAIDs), contrast exposure, or worsening heart failure as potential contributors 2

3. Avoid re-challenge without nephrology input: Given the significant creatinine elevation, re-initiation of Jardiance should only be considered after complete recovery of renal function and with nephrology consultation

4. Monitor for hyperglycemia: After discontinuation, alternative diabetes management will be needed

5. Consider cardiorenal benefit-risk: While SGLT2 inhibitors have proven cardiorenal benefits in patients with chronic kidney disease 4, acute kidney injury supersedes these long-term benefits and requires immediate intervention

By discontinuing Jardiance promptly in response to this significant creatinine elevation, you can prevent further kidney injury and allow for recovery of renal function.