What is the role of Jardiance (empagliflozin) in managing patients with elevated urine albumin-to-creatinine ratio (UACR)?

Jardiance (Empagliflozin) for Elevated UACR

Jardiance should be initiated in all patients with chronic kidney disease and elevated UACR ≥30 mg/g, regardless of diabetes status or albuminuria level, as it provides robust kidney protection and reduces cardiovascular risk across the entire spectrum of albuminuria. 1, 2

Evidence-Based Rationale for SGLT2 Inhibitor Use

The 2025 American Diabetes Association guidelines now position SGLT2 inhibitors as foundational therapy for patients with elevated UACR, moving beyond the traditional ACE inhibitor/ARB-first approach 1. This represents a significant evolution from the 2018 guidelines, which focused primarily on renin-angiotensin system blockade 1.

Kidney Protection Across All UACR Levels

Empagliflozin demonstrates consistent kidney protection regardless of baseline albuminuria, with particularly impressive relative benefits in patients with lower UACR levels. 2

• In the EMPA-KIDNEY trial, empagliflozin reduced the risk of kidney disease progression or cardiovascular death by 28% (HR 0.72,95% CI 0.64-0.82) across all patient types 3
• The chronic eGFR slope was halved from -2.75 to -1.37 mL/min/1.73 m² per year, representing a 50% relative reduction in kidney function decline 2
• Critically, patients with UACR <30 mg/g experienced an 86% reduction in chronic eGFR slope, compared to only 29% reduction in those with UACR ≥2000 mg/g 2
• This paradoxical finding—greater relative benefit at lower albuminuria—challenges the traditional notion that albuminuria level should determine treatment eligibility 2

Cardiovascular Benefits

• Empagliflozin reduced cardiovascular death or heart failure hospitalization by 31% in patients with advanced CKD 1
• The rate of all-cause hospitalization was reduced by 14% (HR 0.86,95% CI 0.78-0.95) 3
• These benefits occurred consistently in patients with or without diabetes and across all eGFR ranges 1, 4

Treatment Algorithm for Elevated UACR

Step 1: Confirm Persistent Albuminuria

• Obtain 2 of 3 abnormal UACR specimens over 3-6 months to confirm persistent elevation, as biological variability exceeds 20% 5, 6
• UACR ≥30 mg/g is considered elevated, with 30-299 mg/g classified as moderately elevated and ≥300 mg/g as severely elevated 5, 6

Step 2: Initiate Empagliflozin 10 mg Daily

• Start empagliflozin immediately upon confirmation of UACR ≥30 mg/g, regardless of diabetes status, blood pressure, or current ACE inhibitor/ARB use 1, 2
• Empagliflozin can be safely initiated with eGFR as low as 20 mL/min/1.73 m² 3
• Expect an acute eGFR dip of approximately 2-3 mL/min/1.73 m² (6% reduction) within the first 2 months—this is hemodynamic, reversible, and does not indicate harm 2, 7

Step 3: Optimize Renin-Angiotensin System Blockade

• For UACR 30-299 mg/g: ACE inhibitor or ARB is recommended (Grade B) 1
• For UACR ≥300 mg/g: ACE inhibitor or ARB is strongly recommended (Grade A) 1
• Titrate to maximum tolerated doses to achieve ≥30% reduction in urinary albumin 5
• Do not combine ACE inhibitors with ARBs or add direct renin inhibitors—this increases adverse events without additional benefit 5, 6

Step 4: Add Finerenone if Needed

• For patients with persistent albuminuria despite SGLT2 inhibitor and ACE inhibitor/ARB at maximum doses, add finerenone (nonsteroidal mineralocorticoid receptor antagonist) 1
• Finerenone is currently the only MRA with proven clinical kidney and cardiovascular benefits in this population 1

Step 5: Optimize Blood Pressure and Glycemic Control

• Target blood pressure <140/90 mmHg (some guidelines suggest <130/80 mmHg for higher-risk patients) 1, 6
• Achieve near-normoglycemia in diabetic patients to delay onset and progression of elevated albuminuria 1, 5
• Consider adding GLP-1 receptor agonists (particularly semaglutide) for additional kidney and cardiovascular protection 1

Monitoring Strategy

• Check serum creatinine/eGFR and potassium at baseline, 7-14 days after empagliflozin initiation, and then at least annually 6
• Monitor UACR twice annually in patients with baseline UACR >30 mg/g to assess treatment response and disease progression 5, 6
• Do not discontinue empagliflozin for the expected acute eGFR dip in the first 2 months unless there is volume depletion or acute kidney injury from another cause 2

Critical Pitfalls to Avoid

The most common error is withholding SGLT2 inhibitors from patients with low or absent albuminuria. 2 The EMPA-KIDNEY trial definitively showed that albuminuria level should not determine eligibility for empagliflozin—patients with UACR <30 mg/g derived substantial relative benefit 2.

• Do not wait for albuminuria to worsen before initiating empagliflozin—earlier intervention provides greater relative kidney protection 2
• Do not discontinue ACE inhibitors/ARBs when starting empagliflozin—these therapies are complementary, not competitive 1
• Avoid metformin dose >1000 mg/day when eGFR <45 mL/min/1.73 m² and discontinue when eGFR <30 mL/min/1.73 m² 5
• Refer to nephrology when eGFR <30 mL/min/1.73 m² or for rapidly progressing kidney disease 1, 5

Special Considerations

• In patients without diabetes, dapagliflozin reduced UACR by 14.8% and showed similar kidney protection across all albuminuria levels 8, 7
• The kidney-protective effects of SGLT2 inhibitors appear partially independent of albuminuria reduction, suggesting mechanisms beyond hemodynamic effects 8
• Empagliflozin demonstrated consistent benefits in patients with non-overt DKD (eGFR <60 without overt albuminuria), a phenotype often undertreated 4