Can Jardiance (empagliflozin) be used for kidney protection in a non-diabetic patient with impaired renal function?

Jardiance (Empagliflozin) for Kidney Protection in Non-Diabetic Patients

Yes, Jardiance (empagliflozin) should be used for kidney protection in non-diabetic patients with chronic kidney disease, provided the eGFR is ≥20 mL/min/1.73 m².

Evidence-Based Rationale

The EMPA-KIDNEY trial definitively established that empagliflozin provides significant renal protection regardless of diabetes status 1. This landmark study included patients with CKD (78% had eGFR <45 mL/min/1.73 m²), and notably, 20% had no pathological albuminuria at baseline 1. The trial demonstrated a 28% reduction in the primary composite outcome of CKD progression or cardiovascular death (p<0.001), with a 33% reduction in progression to end-stage kidney disease 1. Critically, these benefits were consistent in patients both with and without diabetes 1.

The American Diabetes Association 2025 guidelines now recommend empagliflozin for patients with chronic kidney disease and eGFR ≥20 mL/min/1.73 m² to reduce the risk of kidney disease progression and cardiovascular events, explicitly stating this applies regardless of diabetes status 2.

Mechanism of Renal Protection

Empagliflozin protects kidneys through mechanisms independent of glycemic control 2:

• Reduces intraglomerular pressure by increasing afferent arteriolar tone via restoration of tubuloglomerular feedback 2
• Modulates inflammatory response and endothelial activation markers such as NF-κB and e-selectin 3
• Reduces oxidative stress by counteracting upregulation of NADPH oxidases 2 and 4 while preserving antioxidant enzymes 3
• Decreases extracellular matrix accumulation and reduces glomerulosclerosis 3
• Modulates the renin-angiotensin-aldosterone system and ion channels involved in renal homeostasis 3

Clinical Decision Algorithm for Initiation

Step 1: Assess eGFR

• If eGFR ≥45 mL/min/1.73 m²: Initiate empagliflozin 10 mg once daily for renal and cardiovascular protection 2
• If eGFR 20-44 mL/min/1.73 m²: Initiate empagliflozin 10 mg once daily for renal and cardiovascular protection (note: not effective for glycemic control at this level, but renal/cardiovascular benefits are preserved) 2
• If eGFR <20 mL/min/1.73 m²: Do not initiate empagliflozin, but may continue if already on treatment 2
• Do not initiate if eGFR <45 mL/min/1.73 m² per FDA labeling 4, though newer evidence supports initiation down to eGFR ≥20 mL/min/1.73 m² for cardiorenal protection 2

Step 2: Exclude Contraindications

• Severe renal impairment, end-stage renal disease, or dialysis (absolute contraindication per FDA) 4
• History of serious hypersensitivity reaction to empagliflozin 4

Step 3: Assess Volume Status

• Evaluate for volume depletion before initiation, particularly in elderly patients (≥75 years), those on diuretics, or with low systolic blood pressure 4
• Consider reducing concurrent diuretic doses to prevent excessive volume depletion 5

Step 4: Initiate and Monitor

• Start empagliflozin 10 mg once daily in the morning, with or without food 4
• Monitor eGFR and creatinine within 1-2 weeks after initiation to assess the expected transient decrease of 3-5 mL/min/1.73 m² 2
• Continue monitoring eGFR periodically; an initial dip is expected and reversible, followed by slower subsequent decline compared to placebo 2, 6

Dosing Considerations

The dose is fixed at 10 mg once daily for renal and cardiovascular protection 2. Unlike glycemic control where 25 mg may be considered, the renal protection trials (EMPA-KIDNEY, EMPA-REG OUTCOME) used 10 mg 1, 6. No dose titration is required or recommended for cardiorenal indications 2.

Safety Profile in Non-Diabetic Patients

The safety profile of empagliflozin in non-diabetic patients with CKD is comparable to that in diabetic patients 1:

• Genital mycotic infections: Monitor and treat appropriately, though risk is present in both diabetic and non-diabetic patients 4
• Volume depletion: Higher risk in elderly (≥75 years) and those on diuretics; assess volume status before initiation 4
• Urinary tract infections: Increased incidence in elderly patients (15.7% with empagliflozin 10 mg vs 10.5% with placebo in those ≥75 years) 4
• Ketoacidosis: While primarily a concern in diabetic patients, assess for signs of metabolic acidosis regardless of blood glucose level 4
• Acute kidney injury: Paradoxically, empagliflozin was associated with lower occurrence of serious acute kidney injury compared to placebo 7

Critical Safety Precautions

Sick Day Management

• Temporarily discontinue empagliflozin during acute illness, particularly with reduced food/fluid intake, fever, vomiting, or diarrhea 2
• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting 5

Monitoring Parameters

• Recheck eGFR within 1-2 weeks after initiation, then periodically 2
• Monitor for signs of volume depletion, especially in the first few weeks 2
• Assess for genital/urinary infections and educate patients on prevention 5

Common Pitfalls to Avoid

1. Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m² during treatment—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 5

2. Do not confuse glycemic control indications with cardiorenal protection indications—empagliflozin should not be initiated for glycemic control if eGFR <45 mL/min/1.73 m², but can and should be initiated for cardiorenal protection down to eGFR ≥20 mL/min/1.73 m² 2, 4

3. Do not overlook the initial transient eGFR dip—a decrease of 3-5 mL/min/1.73 m² in the first 4 weeks is expected, reversible, and followed by slower subsequent decline 2

4. Do not fail to adjust concurrent medications—consider reducing diuretic doses when initiating empagliflozin to prevent excessive volume depletion 5

Comparison with Other SGLT2 Inhibitors

While dapagliflozin (DAPA-CKD trial) also demonstrated renal protection in non-diabetic patients with a 39% reduction in the primary composite outcome 5, empagliflozin (EMPA-KIDNEY) included a broader population with lower baseline albuminuria (20% without pathological albuminuria) and lower eGFR (78% with eGFR <45 mL/min/1.73 m²) 1. Both agents are appropriate choices, with empagliflozin having the advantage of more recent and broader evidence in advanced CKD 1.

Integration with Existing Therapy

Empagliflozin should be added to, not substituted for, renin-angiotensin system inhibitors (ACE inhibitors or ARBs), which remain first-line therapy for CKD with proteinuria 8. The combination provides complementary mechanisms of renal protection: RAS inhibitors reduce intraglomerular pressure through efferent arteriolar dilation, while empagliflozin reduces intraglomerular pressure through afferent arteriolar constriction via tubuloglomerular feedback 2.