Jardiance (Empagliflozin) in Patients with Low eGFR and Elevated Albumin‑to‑Creatinine Ratio
Jardiance is appropriate and strongly recommended for diabetic patients with reduced eGFR (down to 20 mL/min/1.73 m²) and elevated urine albumin‑to‑creatinine ratio, as it provides robust cardiovascular and renal protection independent of its glucose‑lowering effect. 1
Initiation Criteria Based on eGFR
Initiate Jardiance 10 mg once daily when eGFR ≥20 mL/min/1.73 m² for cardiovascular and renal protection, regardless of diabetes status or baseline HbA1c. 1, 2
For eGFR 20–44 mL/min/1.73 m², start Jardiance solely for cardiorenal protection; glucose‑lowering efficacy is minimal but cardiovascular and renal benefits are fully retained. 2, 3
For eGFR ≥45 mL/min/1.73 m², Jardiance provides both glycemic control and cardiorenal protection at the standard 10 mg dose. 1, 2
Jardiance is contraindicated when eGFR <20 mL/min/1.73 m² according to FDA labeling, though it may be continued (not initiated) if eGFR falls below this threshold in patients already on therapy. 3
Role of Albuminuria in Decision‑Making
Elevated UACR (≥200 mg/g) strengthens the indication for Jardiance, as the EMPA‑KIDNEY trial enrolled patients with UACR ≥200 mg/g and demonstrated a 39% reduction in the composite of kidney disease progression or cardiovascular death. 4
Even patients with UACR <30 mg/g benefit from Jardiance, with an 86% relative reduction in chronic eGFR decline slope compared to 29% in those with UACR ≥2000 mg/g—albuminuria alone should not determine treatment eligibility. 5
The absolute benefit on eGFR slope is smaller in low‑albuminuria patients, but the relative benefit is larger because these patients progress more slowly at baseline. 5
Evidence for Cardiovascular and Renal Protection
In the EMPA‑KIDNEY trial, empagliflozin reduced progression of kidney disease or cardiovascular death by 28% (HR 0.72,95% CI 0.64–0.82) in patients with eGFR as low as 20 mL/min/1.73 m². 4
Empagliflozin halved the chronic eGFR decline slope from −2.75 to −1.37 mL/min/1.73 m² per year (50% relative reduction), with benefits consistent across all eGFR subgroups. 5
Cardiovascular death was reduced by 38% and all‑cause mortality by 32% in the EMPA‑REG OUTCOME trial, which included patients with established atherosclerotic cardiovascular disease. 1, 6
Hospitalization for heart failure was reduced by 31% in patients with type 2 diabetes and chronic kidney disease. 1
Dosing Algorithm
Standard dose: 10 mg orally once daily for all cardiovascular and renal indications; no titration is required. 1, 2
Do not reduce the dose below 10 mg even when eGFR falls below 45 mL/min/1.73 m², as all outcome trials used the fixed 10 mg dose and cardiorenal benefits persist. 1, 2
If the patient is on metformin and eGFR is 30–44 mL/min/1.73 m², continue metformin but limit the dose to ≤1000 mg per day. 1
Pre‑Initiation Assessment
Confirm eGFR ≥20 mL/min/1.73 m² before starting Jardiance. 1, 2
Evaluate volume status and correct any depletion; consider temporary reduction of concurrent loop or thiazide diuretics to prevent excessive volume depletion. 3
Continue ACE inhibitors or ARBs unchanged when Jardiance is started, as >99% of DAPA‑CKD participants were on renin‑angiotensin system blockers and the combination showed additive renal protection. 1
Expected eGFR Changes After Initiation
An acute, reversible eGFR dip of 2–5 mL/min/1.73 m² occurs within the first 2–4 weeks, reflecting hemodynamic changes rather than kidney injury—this should not prompt discontinuation. 5
After the initial dip, eGFR stabilizes and the long‑term decline is slower compared with placebo, indicating net renoprotective effect. 5
Re‑measure eGFR 1–2 weeks after starting Jardiance to document the expected dip, then monitor periodically. 3
Monitoring and Follow‑Up
Check serum creatinine and potassium within 2–4 weeks of initiating Jardiance, especially in patients on ACE inhibitors or ARBs. 3
Monitor eGFR at least every 3–6 months in patients with eGFR <60 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m². 1
Repeat UACR every 3–6 months to assess treatment response and disease progression. 7
Safety Precautions and Patient Education
Temporarily withhold Jardiance during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and stop at least 3 days before major surgery or procedures requiring prolonged fasting to prevent euglycemic diabetic ketoacidosis. 3
Genital mycotic infections occur in approximately 6% of patients versus 1% with placebo; advise daily hygiene to reduce risk. 3, 8
Warn about euglycemic diabetic ketoacidosis and instruct patients to seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 3
If Jardiance must be held temporarily, maintain a low‑dose insulin regimen in insulin‑requiring patients to prevent hyperglycemia. 3
Common Pitfalls to Avoid
Do not discontinue Jardiance when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite loss of glycemic efficacy. 1, 2
Do not stop Jardiance because of the expected initial eGFR dip in the first 2–4 weeks; this change is hemodynamic and reversible. 5
Do not withhold Jardiance solely because of low albuminuria (UACR <30 mg/g); the relative benefit on eGFR slope is actually larger in this subgroup. 5
Do not delay initiation while waiting for "optimal" glycemic control; Jardiance benefits are independent of baseline HbA1c and should be started early as foundational therapy. 1
Integration with Other CKD Therapies
Jardiance should be used alongside ACE inhibitors or ARBs (continued unchanged) as part of first‑line CKD management. 1
Consider adding a GLP‑1 receptor agonist (e.g., semaglutide) for additional cardiovascular and glycemic benefits if eGFR >30 mL/min/1.73 m². 1
Nonsteroidal mineralocorticoid receptor antagonists (e.g., finerenone) can be added if UACR ≥30 mg/g and potassium is normal, providing additive renal benefits. 1