Is it safe to restart Jardiance (Empagliflozin) in a patient with impaired renal function indicated by a Cystatin C level of 3.16?

Restarting Jardiance with Cystatin C of 3.16

Do not restart Jardiance (empagliflozin) with a cystatin C of 3.16 mg/L, as this indicates severely impaired kidney function (eGFR likely <20 mL/min/1.73 m²), which is below the safety threshold established in clinical trials and represents a contraindication to SGLT2 inhibitor therapy.

Assessing Kidney Function with Cystatin C 3.16

Your cystatin C level of 3.16 mg/L is markedly elevated and indicates severe kidney dysfunction 1, 2:

• The reference point for the 2012 CKD-EPI cystatin C equation is 0.8 mg/L 1
• A cystatin C of 3.16 mg/L is approximately 4 times the reference value, suggesting eGFR is likely well below 30 mL/min/1.73 m² and possibly approaching 15-20 mL/min/1.73 m² (Stage 4-5 CKD) 3
• Cystatin C is independent of muscle mass, making it particularly reliable for detecting true kidney dysfunction 1, 2

Why Jardiance Should Not Be Restarted

Evidence from Clinical Trials

The major empagliflozin trials excluded or showed minimal benefit in severe kidney impairment:

• EMPA-REG OUTCOME required eGFR ≥30 mL/min/1.73 m² for enrollment, and your cystatin C suggests function below this threshold 4
• EMPA-KIDNEY enrolled patients with eGFR as low as 20 mL/min/1.73 m² but demonstrated that efficacy diminishes substantially at lower kidney function 5
• Urinary glucose excretion (the mechanism of action) decreases dramatically with declining kidney function: in Japanese patients with severe renal impairment (eGFR 15-30), glucose excretion was only 23.7g compared to 75.0g in normal function 6

Pharmacokinetic Concerns

• Empagliflozin exposure increases by 52% in severe renal impairment (eGFR 15-30 mL/min/1.73 m²) compared to normal function 6
• Renal clearance of empagliflozin correlates directly with eGFR, meaning drug elimination is significantly impaired at your level of kidney function 6
• The therapeutic benefit is lost while exposure-related risks persist 6

Immediate Next Steps

1. Confirm Kidney Function with Combined Assessment

Calculate eGFR using both creatinine and cystatin C to obtain the most accurate assessment 1, 2:

• Request simultaneous serum creatinine and cystatin C measurement 1
• Calculate all three eGFR values: eGFRcreat, eGFRcys, and eGFRcreat-cys (the combined equation, which is most accurate) 1, 7
• The combined equation has 94.9% accuracy within 30% of measured GFR 1

2. Investigate Causes of Elevated Cystatin C

While cystatin C is largely GFR-dependent, certain conditions can affect levels independently 2, 7:

• Check thyroid function (TSH): hypothyroidism increases cystatin C independent of GFR 2, 7
• Assess for active smoking: can elevate cystatin C 2, 7
• Review corticosteroid use: high-dose steroids may affect levels 2
• Evaluate for malignancy: high cell turnover cancers can influence cystatin C 7

3. Assess for Intrinsic Kidney Disease

Obtain urinalysis with microscopy and spot urine albumin-to-creatinine ratio 3, 2:

• Look for hematuria, cellular casts, or proteinuria indicating glomerular or tubular disease 3
• Albuminuria >300 mg/g indicates significant kidney damage and cumulative risk with reduced eGFR 3
• These findings help distinguish reversible hemodynamic changes from irreversible intrinsic disease 3

Alternative Management Strategies

If eGFR Confirms <20 mL/min/1.73 m²

Jardiance is contraindicated and should not be restarted 4, 5:

• Focus on blood pressure control targeting <130/80 mmHg for cardiovascular risk reduction 2
• Optimize other guideline-directed medical therapy for heart failure or diabetes as appropriate
• Consider nephrology referral for advanced CKD management and potential renal replacement therapy planning 3

If eGFR is 20-30 mL/min/1.73 m² (Stage 4 CKD)

Jardiance may be considered but with extreme caution 5:

• EMPA-KIDNEY included patients down to eGFR 20 mL/min/1.73 m² and showed benefit, but efficacy was reduced 5
• The therapeutic effect (glucose excretion) is markedly diminished at this level 6
• Close monitoring for volume depletion and acute kidney injury is essential
• Shared decision-making is critical, weighing minimal expected benefit against potential risks

If eGFR is 30-45 mL/min/1.73 m² (Stage 3b CKD)

Jardiance can be continued with appropriate monitoring 4, 8, 5:

• EMPEROR-Reduced and EMPA-KIDNEY demonstrated cardiovascular and kidney benefits in this range 8, 5
• Monitor kidney function every 3-6 months 3
• Educate about sick day rules (hold during acute illness with volume depletion)

Common Pitfalls to Avoid

• Do not rely solely on serum creatinine in patients with low muscle mass, as it may underestimate kidney dysfunction 3, 1
• Do not restart SGLT2 inhibitors during acute kidney injury or volume depletion, as this increases risk of further deterioration 3
• Do not ignore the cystatin C value of 3.16 mg/L – this represents severe dysfunction regardless of what creatinine shows 1, 2
• Do not assume benefit from empagliflozin at very low eGFR – the mechanism of action (urinary glucose excretion) requires adequate kidney function 6