Is Jardiance (Empagliflozin) recommended for patients with Chronic Kidney Disease (CKD) without diabetes?

Is Jardiance Recommended for CKD Without Diabetes?

Yes, Jardiance (empagliflozin) is strongly recommended for patients with chronic kidney disease without diabetes, particularly when eGFR is ≥20 mL/min/1.73 m² and there is significant albuminuria (ACR ≥200 mg/g) or heart failure. 1

Evidence-Based Recommendations by CKD Severity

Strong Recommendation (Level 1A)

KDIGO guidelines provide the highest level recommendation for SGLT2 inhibitors including empagliflozin in adults with CKD having:

• eGFR ≥20 mL/min/1.73 m² AND
• Urine albumin-to-creatinine ratio ≥200 mg/g, OR
• Heart failure (regardless of albuminuria level) 1

This recommendation applies irrespective of diabetes status 1

Moderate Recommendation (Level 2B)

For patients with:

• eGFR 20-45 mL/min/1.73 m² AND
• Urine ACR <200 mg/g (lower albuminuria)

SGLT2 inhibitors are suggested but with slightly less certainty 1

Landmark Trial Evidence in Non-Diabetic CKD

EMPA-KIDNEY Trial (2023) - The Definitive Study

This is the most recent and highest-quality evidence specifically addressing your question. The trial enrolled 6,609 patients with CKD (with or without diabetes) and demonstrated:

Primary Outcome Results:

• 28% reduction (HR 0.72,95% CI 0.64-0.82, P<0.001) in the composite of kidney disease progression or cardiovascular death 2
• 33% reduction in progression to end-stage kidney disease 3
• Results were consistent in patients with or without diabetes 2

Key Trial Design Features:

• 78% of patients had eGFR <45 mL/min/1.73 m² (more advanced CKD than prior trials) 3
• 20% of patients had no pathological albuminuria (expanding the indication beyond just albuminuric CKD) 3
• Median follow-up of 2.0 years 2

Additional Benefits:

• 14% reduction in hospitalization from any cause (HR 0.86,95% CI 0.78-0.95, P=0.003) 2
• Slowed decline in kidney function across all eGFR ranges 2
• Safety profile comparable to placebo 3, 2

Practical Initiation and Monitoring Guidelines

When to Start

• Initiate when eGFR ≥20 mL/min/1.73 m² 1
• Assess volume status before starting; correct volume depletion if present 4
• FDA labeling technically states not to initiate if eGFR <45 mL/min/1.73 m², but clinical trial evidence (EMPA-KIDNEY) supports use down to eGFR 20 4, 2

Dosing

• Standard dose: 10 mg once daily in the morning, with or without food 4
• This is the dose used in EMPA-KIDNEY for kidney protection 2
• The 25 mg dose is primarily for additional glycemic control in diabetics 4

When to Continue vs. Discontinue

• Continue empagliflozin even if eGFR falls below 20 mL/min/1.73 m² after initiation, unless not tolerated or kidney replacement therapy is started 1
• This represents a paradigm shift from older FDA guidance 4

When to Temporarily Withhold

Withhold during:

• Prolonged fasting 1
• Surgical procedures 1
• Critical medical illness 1
• Reason: Increased risk of ketoacidosis in these settings 4

Important Safety Considerations

Monitoring Requirements

• Assess renal function before initiation and periodically thereafter 4
• Monitor for volume depletion, especially in:
  • Elderly patients (≥75 years: 4.4% risk with 25 mg dose) 4
  • Patients on diuretics 4
  • Those with low baseline systolic blood pressure 4

Common Adverse Effects to Monitor

• Genital mycotic infections 1
• Urinary tract infections (15.7% in patients ≥75 years) 4
• Volume depletion and hypotension 4
• Ketoacidosis risk (rare but serious) 4

Mechanism of Kidney Protection in Non-Diabetics

The renoprotective effects occur through mechanisms independent of glycemic control:

• Restoration of tubuloglomerular feedback 5
• Reduction in intraglomerular pressure by increasing afferent arteriolar tone 5
• Decreased renal tubular glucose reabsorption 5
• Reduction in systemic blood pressure 5
• Decreased albuminuria 5
• Reduction in oxidative stress (>50% reduction) 5
• Decreased NLRP3 inflammasome activity 5

These mechanisms explain why empagliflozin provides kidney protection even in patients without diabetes 6, 2

Comparison with Other CKD Treatments

Combination with RAS Inhibitors

• Empagliflozin should be used in addition to (not instead of) ACE inhibitors or ARBs in patients with albuminuria 3
• The kidney benefits of empagliflozin are consistent regardless of background use of ACE inhibitors, ARBs, calcium channel blockers, or diuretics 7
• No increased risk of acute renal adverse events when combined with these medications 7

Advantages Over Traditional Therapies

• Unlike metformin, empagliflozin has direct documented kidney benefit 5
• Provides cardiovascular protection in addition to kidney protection 2
• Low risk of hypoglycemia (not applicable in non-diabetics anyway) 5

Clinical Bottom Line

Empagliflozin 10 mg daily should be initiated in non-diabetic CKD patients with eGFR ≥20 mL/min/1.73 m² who have either significant albuminuria (ACR ≥200 mg/g) or heart failure. 1, 2 The EMPA-KIDNEY trial provides Level 1 evidence that this approach reduces kidney disease progression by 28% and end-stage kidney disease by 33%, with benefits independent of diabetes status. 3, 2 Once started, continue the medication even if eGFR declines below 20, unless dialysis is initiated or the patient cannot tolerate it. 1