Is Empagliflozin Indicated in Chronic Kidney Disease?
Yes, empagliflozin is strongly indicated for chronic kidney disease and should be initiated in patients with eGFR ≥20 mL/min/1.73 m² to reduce kidney disease progression and cardiovascular death, regardless of diabetes status. 1, 2
Evidence-Based Indications
Empagliflozin reduces the risk of kidney disease progression or cardiovascular death by 28% in patients with CKD, with consistent benefits across the full spectrum of kidney function down to eGFR 20 mL/min/1.73 m². 1, 2 The landmark EMPA-KIDNEY trial demonstrated a 24% reduction in major renal events including sustained eGFR decline >50%, progression to dialysis, transplantation, or renal/cardiovascular death. 1
Key Clinical Benefits:
- Reduces progression to end-stage kidney disease by 33% 3
- Slows annual eGFR decline after an initial transient 3-5 mL/min/1.73 m² dip in the first 4 weeks 1
- Reduces cardiovascular death by 38% in patients with established cardiovascular disease 4
- Decreases hospitalization from any cause by 14% (HR 0.86,95% CI 0.78-0.95) 2
Clinical Decision Algorithm by eGFR
eGFR ≥45 mL/min/1.73 m²:
- Initiate empagliflozin 10 mg once daily for both renal/cardiovascular protection AND glycemic control (if diabetic) 1
- No dose adjustment required 5
eGFR 20-44 mL/min/1.73 m²:
- Initiate empagliflozin 10 mg once daily for renal/cardiovascular protection ONLY 1
- Do NOT rely on empagliflozin for glycemic control in this range, as glucose-lowering efficacy is significantly reduced 4
- This is where empagliflozin shows the MOST dramatic benefit—78% of EMPA-KIDNEY participants had eGFR <45 mL/min/1.73 m² 3
eGFR <20 mL/min/1.73 m²:
- Do NOT initiate empagliflozin 1
- However, CONTINUE empagliflozin if already on treatment until dialysis is required 4
Mechanism of Renal Protection
Empagliflozin protects kidneys through multiple mechanisms independent of glycemic control: 1, 6
- Restores tubuloglomerular feedback, reducing intraglomerular pressure by increasing afferent arteriolar tone 4
- Reduces oxidative stress in the kidney by >50% 6
- Decreases systemic blood pressure and albuminuria 6
- Reduces NLRP3 inflammasome activity 6
Critically, these renal benefits occur regardless of diabetes status—EMPA-KIDNEY included patients both with and without diabetes, showing consistent efficacy. 2
Albuminuria Considerations
Unlike dapagliflozin trials (DAPA-CKD), EMPA-KIDNEY included 20% of patients WITHOUT pathological albuminuria, making empagliflozin's indication broader. 3 This means:
- Empagliflozin is indicated even in non-albuminuric CKD with eGFR 20-44 mL/min/1.73 m² 3
- Benefits are consistent whether UACR is <200 mg/g or >300 mg/g 7
The 2022 ADA/KDIGO consensus specifically states empagliflozin can be initiated for patients with eGFR ≥20 mL/min/1.73 m² with concomitant albuminuria OR heart failure, though efficacy is generally consistent without these conditions. 4
Dosing and Administration
Fixed dose: 10 mg once daily in the morning 1
- No titration required 1
- May be taken with or without food 5
- No dose adjustment needed based on renal function at initiation (as long as eGFR ≥20) 5
Monitoring Requirements
Initial Monitoring:
- Check eGFR and creatinine within 1-2 weeks after initiation to assess the expected transient decrease 1
- Assess volume status before starting and monitor for signs of volume depletion in the first few weeks 1
Expected eGFR Changes:
- Anticipate a reversible 3-5 mL/min/1.73 m² decrease in the first 4 weeks—this is hemodynamic, not nephrotoxic 1
- Do NOT discontinue empagliflozin if eGFR falls below initiation threshold unless patient is not tolerating treatment or requires dialysis 4
- After initial dip, empagliflozin significantly slows subsequent eGFR decline compared to placebo 7
Critical Safety Precautions
Sick Day Protocol (ESSENTIAL):
- Stop empagliflozin during acute illness with reduced food/fluid intake, fever, vomiting, or diarrhea 1
- Maintain at least low-dose insulin in insulin-requiring patients even when empagliflozin is held 4
- Risk of euglycemic diabetic ketoacidosis, particularly in insulin-requiring patients 4
Volume Depletion:
- More common in patients on diuretics, elderly, or those with low baseline blood pressure 4
- Consider reducing diuretic doses when initiating empagliflozin 4
Genital Mycotic Infections:
- Occur in 6% of SGLT2i patients vs. 1% on placebo 4
- Daily hygienic measures may reduce risk 4
- Rare but serious: Fournier gangrene requires immediate treatment if suspected 4
Hypoglycemia:
- Adjust background sulfonylureas or insulin as appropriate when initiating 4
- Absolute hypoglycemia risk is low, especially at lower eGFR 4
Compatibility with Other Renal Medications
Empagliflozin's renal benefits are consistent regardless of background medications that alter intrarenal hemodynamics, including: 8
- ACE inhibitors/ARBs
- Calcium channel blockers
- Diuretics
- NSAIDs (though NSAID use should generally be minimized in CKD)
The risk reduction for incident or worsening nephropathy with empagliflozin was consistent across all medication subgroups with no heterogeneity of treatment effect. 8
Common Pitfalls to Avoid
Do NOT discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 4
Do NOT panic about the initial eGFR dip—this is expected, reversible, and does NOT indicate kidney injury 1
Do NOT withhold empagliflozin in non-diabetic CKD patients—EMPA-KIDNEY proved benefit regardless of diabetes status 2
Do NOT forget sick day rules—failure to hold empagliflozin during acute illness is a major cause of preventable ketoacidosis 1
Do NOT rely on empagliflozin for glycemic control when eGFR <45 mL/min/1.73 m²—use it for renal/cardiovascular protection only in this range 1
Regulatory Approval
The FDA approved empagliflozin to reduce the risk of major adverse cardiovascular death in adults with type 2 diabetes and cardiovascular disease. 4 The 2025 ADA guidelines now recommend empagliflozin for CKD patients with eGFR ≥20 mL/min/1.73 m² for renal and cardiovascular protection. 1