Jardiance (Empagliflozin) and Renal Injury
Direct Answer
Jardiance does not cause renal injury and actually protects the kidneys—it can be safely initiated in patients with chronic kidney disease down to an eGFR of 20 mL/min/1.73 m² and should be continued even if kidney function declines during treatment. 1, 2
Key Safety Principle: Initial eGFR Dip is Expected and Protective
An initial reversible decline in eGFR of 3-5 mL/min/1.73 m² typically occurs within the first 1-4 weeks of starting Jardiance—this is a hemodynamic effect, not kidney injury, and paradoxically predicts better long-term renal outcomes. 3
- Patients experiencing this initial eGFR dip actually had slower long-term eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) compared to those without an initial dip 3
- Check eGFR within 1-2 weeks after initiation to document this expected change 3
- Do not discontinue Jardiance for this initial dip unless eGFR decreases >30% from baseline AND there are signs of hypovolemia 3
Initiation Guidelines Based on eGFR
For Glycemic Control
- Do not initiate if eGFR <45 mL/min/1.73 m² as glucose-lowering efficacy is significantly reduced 1
- Start at 10 mg once daily if eGFR ≥45 mL/min/1.73 m², with option to increase to 25 mg if additional glycemic control needed 1
For Cardiovascular and Renal Protection
- Initiate at 10 mg once daily if eGFR ≥20 mL/min/1.73 m² regardless of diabetes status 4, 2
- The 2025 ADA guidelines now support initiation down to eGFR 20 mL/min/1.73 m² (updated from previous 25 mL/min/1.73 m² threshold) 4
- No dose adjustment needed—10 mg daily is the fixed dose for cardiovascular/renal protection 3
Continuation During Declining Renal Function
Never discontinue Jardiance solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 4, 3
- Continue 10 mg daily even if eGFR falls below 25 mL/min/1.73 m² until dialysis is required 3, 1
- The FDA label states discontinuation if eGFR is "persistently" <45 mL/min/1.73 m² for glycemic control, but this does not apply to cardiovascular/renal indications 1
Proven Renal Protection: The Evidence
EMPA-KIDNEY Trial (2023)
- Jardiance reduced progression of kidney disease or cardiovascular death by 28% (HR 0.72,95% CI 0.64-0.82) in patients with eGFR 20-90 mL/min/1.73 m² 2
- Kidney-specific outcomes: 40% sustained eGFR decline, end-stage kidney disease, or renal death reduced by 44% 2
- Benefits were consistent in patients with and without diabetes 2
EMPA-REG OUTCOME Renal Analysis (2016)
- Incident or worsening nephropathy reduced by 39% (HR 0.61,95% CI 0.53-0.70) 5
- Doubling of serum creatinine reduced by 44% 5
- Initiation of renal replacement therapy reduced by 55% 5
Chronic eGFR Slope Benefit
- Jardiance slowed chronic eGFR decline by 50% (1.37 mL/min/1.73 m²/year difference) across all primary kidney diseases including diabetic kidney disease, glomerular disease, and hypertensive nephropathy 6
When to Temporarily Hold Jardiance: Acute Illness Protocol
Withhold Jardiance during any acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and euglycemic diabetic ketoacidosis. 4, 3
Specific Situations Requiring Temporary Discontinuation:
- Acute illness requiring hospitalization 4
- Reduced ability to eat or drink normally 3
- Fever, vomiting, or diarrhea 3
- At least 3 days before major surgery or procedures with prolonged fasting 3
- Urinary tract infection requiring hospitalization 3
Critical Monitoring During Illness:
- Monitor for diabetic ketoacidosis (DKA) even with normal blood glucose levels—euglycemic DKA can occur 4, 1
- Check blood or urine ketones if patients develop malaise, nausea, or vomiting 3
- Maintain at least low-dose insulin in insulin-requiring patients even when Jardiance is held 3
When to Restart:
- Resume only after recovery from acute illness and normal oral intake is re-established 3
Volume Depletion Risk Management
Assess volume status before starting Jardiance and correct any volume depletion, particularly in elderly patients, those on diuretics, or with low systolic blood pressure. 1
- Consider reducing concurrent diuretic doses when initiating Jardiance to prevent excessive volume depletion 3
- Monitor for signs of hypotension after initiation, especially in patients with eGFR <60 mL/min/1.73 m² 1
- If eGFR decreases >30% from baseline with signs of hypovolemia, reduce diuretic doses first before adjusting Jardiance 3
Monitoring Schedule
- Check eGFR before initiation and within 1-2 weeks after starting 3
- Recheck eGFR every 3-6 months if eGFR 45-59 mL/min/1.73 m² 3
- Annual eGFR monitoring if eGFR ≥60 mL/min/1.73 m² 3
- Assess volume status at each visit, particularly in elderly patients 1
Common Pitfalls to Avoid
Discontinuing Jardiance when eGFR falls below 45 mL/min/1.73 m²: The cardiovascular and renal benefits persist at lower eGFR levels even though glycemic efficacy decreases 4, 3
Mistaking the initial eGFR dip for acute kidney injury: This hemodynamic effect is expected and protective, not harmful 3
Continuing Jardiance during acute illness: Always hold during illness with reduced oral intake to prevent DKA and volume depletion 4, 3
Not reducing diuretic doses when initiating: Proactively reduce diuretics in patients at high risk for volume depletion 3
Assuming normal glucose rules out DKA: Euglycemic DKA can occur with glucose <250 mg/dL in patients on SGLT2 inhibitors 1
Additional Safety Considerations
- Genital mycotic infections occur in approximately 6% of patients (vs 1% on placebo)—counsel patients on hygiene measures 3, 7
- Urinary tract infections are more common—evaluate and treat promptly 1
- Rare but serious: Fournier's gangrene (necrotizing fasciitis of the perineum) requires immediate treatment if suspected 3
- No increased hypoglycemia risk when used alone, but consider reducing insulin or sulfonylurea doses by ~20% when initiating 7