Should I hold empagliflozin (Jardiance) in a patient with heart failure with reduced ejection fraction who has acute kidney injury and a creatinine level of 1.5–2.1 mg/dL?

Do Not Hold Empagliflozin (Jardiance) in This Clinical Scenario

Continue empagliflozin in this patient with HFrEF and a creatinine rise from 1.5 to 2.1 mg/dL in the setting of AKI. 1 This modest creatinine elevation does not represent true tubular injury requiring drug discontinuation, but rather reflects hemodynamic changes from decongestion or the expected initial "dip" in eGFR that occurs with SGLT2 inhibitor initiation.

Key Clinical Context: Distinguishing Hemodynamic Changes from True Kidney Injury

The most critical determination is whether this creatinine rise represents:

• Hemodynamic alteration (decongestion, cardiorenal syndrome, RAAS inhibitor effect) - does not require stopping empagliflozin
• True acute tubular necrosis (sepsis, bleeding, nephrotoxins) - may require temporary hold

The 2025 American Journal of Kidney Diseases guideline explicitly addresses this exact scenario 1: A 45-year-old woman with HFrEF on empagliflozin whose creatinine increased from 1.2 to 1.5 mg/dL while NT-proBNP improved from 1,400 to 900 pg/mL. The correct answer was (a) Continue lisinopril and empagliflozin. The guideline emphasizes that urine microscopy has excellent negative predictive value for ruling out clinically important intrinsic kidney injury.

Why Empagliflozin Should Be Continued

1. Expected Initial eGFR Dip is Protective, Not Harmful

• SGLT2 inhibitors cause a reversible 10-15% decline in eGFR within the first 2-4 weeks 2, 3
• This initial dip does not represent tubular damage 4 and resolves within 1-3 months 2
• The mechanism is hemodynamic: reduced intraglomerular pressure through afferent arteriolar vasoconstriction 4
• Long-term kidney protection occurs despite this initial dip - slower eGFR decline over time 2, 5

2. SGLT2 Inhibitors Actually Protect Against AKI

The 2022 ADA/KDIGO guideline states: "SGLT2i use appears to protect patients from AKI" 3. In the EMPULSE trial of patients hospitalized with acute heart failure, investigator-reported acute renal failure occurred in 7.7% of empagliflozin patients versus 12.1% of placebo patients 6.

3. Continuation is Recommended Even When eGFR Falls Below Initiation Thresholds

Both CREDENCE and DAPA-CKD trial protocols specified continuation of study drug when eGFR fell below initiation thresholds 3. The guideline explicitly states: "Therefore, it is reasonable to continue therapy if the eGFR falls below the initiation thresholds unless the patient is not tolerating treatment or KRT is initiated."

4. Your Patient's Creatinine Range Remains Within Safe Limits

• Empagliflozin is approved for use down to eGFR ≥20 mL/min/1.73 m² 7
• A creatinine of 2.1 mg/dL typically corresponds to eGFR 30-40 mL/min/1.73 m² (depending on age/sex)
• The EMPEROR-Reduced trial enrolled patients with eGFR as low as 20 mL/min/1.73 m² 2
• No dose adjustment is needed 7

When to Actually Hold SGLT2 Inhibitors

Empagliflozin should be held in these specific situations:

Absolute Indications to Hold:

• Sick day protocol: Acute dehydrating illness, vomiting, diarrhea 2
• True acute tubular necrosis: Confirmed by urine microscopy showing muddy brown casts, renal tubular epithelial cells 1
• Sepsis or hemorrhagic shock requiring vasopressors
• Diabetic ketoacidosis (though rare with empagliflozin) 2
• Severe volume depletion with hypotension

Relative Considerations (Not Absolute):

• eGFR <20 mL/min/1.73 m² (insufficient data, though recent studies suggest safety) 7, 8
• Dialysis initiation (contraindicated) 7

Practical Management Algorithm

For your patient with creatinine 1.5→2.1:

1. Assess volume status clinically

   • If euvolemic or hypervolemic → continue empagliflozin
   • If severely hypovolemic → hold temporarily, reassess after rehydration

2. Check urine microscopy 1

   • No casts/cells → hemodynamic change, continue empagliflozin
   • Muddy brown casts → ATN, hold temporarily

3. Evaluate for sick day triggers

   • Vomiting/diarrhea → hold temporarily
   • Stable oral intake → continue

4. Monitor trend, not single value

   • Stable creatinine 2.0-2.1 → continue
   • Rapidly rising (>0.5 mg/dL/day) → investigate cause, may hold temporarily

5. Assess NT-proBNP/clinical improvement 1

   • Improving HF symptoms + rising creatinine = decongestion → continue
   • Worsening HF + rising creatinine = true deterioration → investigate

Critical Pitfalls to Avoid

Do not reflexively stop empagliflozin for modest creatinine elevation. This is the most common error. The 2021 Canadian guidelines warn that "SGLT2 inhibitor use might result in temporary reduction of eGFR up to 15%, which generally resolves within 1-3 months" and that "increased monitoring is warranted" - not discontinuation 2.

Do not confuse hemodynamic eGFR changes with kidney injury. The 2025 AJKD guideline specifically illustrates this distinction, showing that creatinine increases during decongestion or with RAAS inhibitors occur without actual tubular damage 1.

Do not withhold mortality-reducing therapy based on laboratory values alone. Empagliflozin reduces cardiovascular death by 18-31% in HFrEF 2. The risk of withholding this therapy far exceeds the risk of a transient, reversible creatinine elevation.

Monitoring Strategy

• Recheck creatinine in 1 week 2
• Continue empagliflozin unless creatinine continues rising rapidly or patient develops true AKI symptoms
• Adjust diuretics if needed - the combination of SGLT2i, RAAS inhibitors, and loop diuretics requires attention to volume status 2
• Educate patient on sick day management - hold empagliflozin during acute illnesses with vomiting/diarrhea 2

The evidence overwhelmingly supports continuation of empagliflozin in your patient, as the mortality and morbidity benefits in HFrEF persist across the entire spectrum of kidney function, and the modest creatinine elevation likely represents beneficial hemodynamic effects rather than kidney injury.