Empagliflozin Use in Chronic Kidney Disease (eGFR ≥ 20 mL/min/1.73 m²) – KDIGO Guideline Summary

Initiation Criteria

Empagliflozin should be started in adults with chronic kidney disease when estimated glomerular filtration rate (eGFR) is ≥ 20 mL/min/1.73 m², irrespective of diabetes status.  [1]
Strong recommendation (Grade 1A) for initiating empagliflozin in:
- Adults with type 2 diabetes and CKD, eGFR ≥ 20 mL/min/1.73 m². [5]
- Adults with CKD and albuminuria ≥ 200 mg/g, eGFR ≥ 20 mL/min/1.73 m², regardless of diabetes. [1]
- Adults with heart failure (any albuminuria) and eGFR ≥ 20 mL/min/1.73 m². [1]
Conditional recommendation (Grade 2B) for patients with eGFR 20‑45 mL/min/1.73 m² and albuminuria < 200 mg/g. [1]
Empagliflozin must not be initiated in patients with persistently eGFR < 20 mL/min/1.73 m² or who are receiving chronic dialysis. [1]

The standard dose is 10 mg once daily, taken in the morning with or without food. [5]
No dose adjustment is required for eGFR 30‑44 mL/min/1.73 m²; continue 10 mg daily. [5]
For eGFR < 30 mL/min/1.73 m², despite FDA labeling that discourages glucose‑lowering use, KDIGO recommends continuing 10 mg daily for renal and cardiovascular protection. [1]
The higher 25 mg dose provides no additional renal or cardiovascular benefit at lower eGFR levels and is not more effective for glucose lowering in advanced CKD. [5]

Once therapy is started, continue empagliflozin even if eGFR falls below the 20 mL/min/1.73 m² initiation threshold, unless the drug is not tolerated or the patient initiates dialysis. [1]

Measure eGFR and evaluate volume status before initiation. [8]
Identify patients at risk for volume depletion (e.g., older adults, low systolic blood pressure, concurrent diuretic use) and consider proactive diuretic dose reduction. [5]
Review concomitant medications for potential interactions. [8]

An acute, reversible decline of 2‑6 % in eGFR (≈ 2 mL/min/1.73 m²) is typical during the first two months; this hemodynamic dip should not trigger discontinuation. [1]

Assess volume status and blood pressure at each follow‑up visit, especially during the initial weeks. [5]
Continue routine CKD monitoring schedule for eGFR; no extra frequency is required solely because empagliflozin was started. [1]
Check for ketone bodies only if symptoms of ketoacidosis develop (nausea, vomiting, abdominal pain, malaise). [5]
Adjust insulin or sulfonylurea doses only if hypoglycemia occurs; routine glucose‑lowering adjustments are generally unnecessary. [5]

Volume depletion risk remains low even at low eGFR, but monitor for hypotension and consider diuretic dose reduction in high‑risk patients. [5]
Ketoacidosis prevention:
- Withhold empagliflozin during prolonged fasting, surgery, or critical illness. [1]
- For insulin‑requiring patients, maintain at least a low‑dose insulin regimen to reduce ketoacidosis risk. [5]
- Euglycemic diabetic ketoacidosis can occur with blood glucose < 250 mg/dL. [5]
Genital mycotic infections occur in ≈ 6 % of treated patients (vs 1 % with placebo); counsel on genital hygiene. [5]
Hypoglycemia risk is low, especially at low eGFR where glucose‑lowering effect wanes; background glucose‑lowering agents may be modestly adjusted if needed. [5]

Do not discontinue empagliflozin for the expected acute eGFR dip unless serum creatinine rises > 30 % from baseline. [2]
Do not withhold initiation based solely on low albuminuria; benefits extend to patients with minimal albuminuria. [1]
Do not stop empagliflozin when eGFR falls below 20 mL/min/1.73 m² if the patient is already on therapy. [1]
Do not rely on outdated FDA labeling that restricts use below eGFR 45 mL/min/1.73 m²; current evidence supports use down to eGFR 20. [5]
Pause empagliflozin during acute illness, surgery, or prolonged fasting to lower ketoacidosis risk. [1]

Kidney transplant recipients: Empagliflozin has not been adequately studied in this group due to immunosuppression and infection concerns; the current recommendation does not apply. [2]
Patients without diabetes: Initiation and monitoring principles are identical, as trial data demonstrate consistent renal and cardiovascular benefits irrespective of diabetes status. [1]