Empagliflozine for Chronic Kidney Disease

Indications and Benefits

The American Diabetes Association recommends Empagliflozine for patients with chronic kidney disease and an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m² to reduce the risk of kidney disease progression and cardiovascular events 1
Empagliflozine reduces the risk of major renal events, including a sustained decline of >50% in eGFR, eGFR <15 mL/min/1.73 m², dialysis, transplantation, or renal/cardiovascular death, by 24% in the EMPA-KIDNEY trial 1
The American Diabetes Association 2025 guidelines suggest that Empagliflozine can be initiated with an eGFR ≥20 mL/min/1.73 m² for renal and cardiovascular protection 1

Empagliflozine protects the kidneys through several mechanisms independent of glycemic control, including reducing intraglomerular pressure by increasing afferent arteriolar tone via restoration of tubuloglomerular feedback 2
Empagliflozine slows the decline in eGFR after an initial transient and reversible decrease of 3-5 mL/min/1.73 m² in the first 4 weeks 3

If eGFR ≥45 mL/min/1.73 m², Empagliflozine can be used for both glycemic control and renal/cardiovascular protection 1
If eGFR 20-44 mL/min/1.73 m², Empagliflozine is recommended only for renal/cardiovascular protection (not for glycemic control) 1
If eGFR <20 mL/min/1.73 m², Empagliflozine should not be initiated, but can be continued if already being treated 1

The recommended dose is 10 mg once daily in the morning for heart failure and renal protection 3

Monitor eGFR and creatinine within 1-2 weeks after initiation to assess the expected transient decrease 3
Educate patients on sick day rules: stop Empagliflozine during acute illness with reduced food/hydration intake 3
Monitor for signs and symptoms of volume depletion, particularly in the first few weeks 3

The American Diabetes Association recommends initiating empagliflozin at eGFR ≥20 mL/min/1.73 m² for renal and cardiovascular protection, with benefits persisting across the spectrum of kidney function down to eGFR ≥20 mL/min/1.73 m² 4

Empagliflozin slows the subsequent rate of eGFR decline compared to placebo, with a significant reduction in the composite kidney outcome by 47-54% in patients with and without baseline chronic kidney disease 4
The EMPA-KIDNEY trial demonstrated a 28% reduction in progression of kidney disease or cardiovascular death (HR 0.72, 95% CI 0.64-0.82) in patients with eGFR as low as 20 mL/min/1.73 m² 4

The American Diabetes Association recommends 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, regardless of diabetes status 5

Empagliflozin protects kidneys through mechanisms independent of glycemic control, including reducing intraglomerular pressure, modulating inflammatory response, reducing oxidative stress, decreasing extracellular matrix accumulation, and modulating the renin-angiotensin-aldosterone system 5

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, as the combination provides complementary mechanisms of renal protection 5

In patients with reduced kidney function (e.g., eGFR ≈ 38 mL/min/1.73 m²) who start empagliflozin for cardiovascular or renal protection, the transient 3–5 mL/min/1.73 m² decline in eGFR observed during the first 2–4 weeks should not lead to drug discontinuation; cessation is only warranted if there are signs of true tubular injury, which can be assessed with urine microscopy. 6