Jardiance Does Not Cause Proteinuria—It Reduces It
Jardiance (empagliflozin) does not cause proteinuria; rather, it significantly reduces proteinuria and slows kidney disease progression in patients with chronic kidney disease, including those with pre-existing kidney disease. 1
Evidence from Major Clinical Trials
The American Diabetes Association guidelines, based on the landmark EMPA-REG OUTCOME trial, demonstrate that empagliflozin:
- Reduced the risk of incident or worsening nephropathy by 39% (composite outcome including progression to urinary albumin-to-creatinine ratio >300 mg/g, doubling of serum creatinine, end-stage renal disease, or death from ESRD) 1
- Reduced the risk of doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73 m² by 44% 1
- Reduces albuminuria and slows GFR loss through mechanisms independent of glycemic control, including reduction of intraglomerular pressure 1
Mechanism of Renal Protection
SGLT2 inhibitors like empagliflozin provide kidney protection through multiple direct effects:
- Reduce renal tubular glucose reabsorption 1
- Lower intraglomerular pressure 1
- Decrease albuminuria 1
- Reduce systemic blood pressure and weight 1
- Slow GFR loss through mechanisms independent of glucose lowering 1
Real-World Clinical Evidence
Recent research confirms these protective effects in clinical practice:
- Empagliflozin reduced proteinuria in patients with non-diabetic glomerulonephritis when added to standard therapy (RAAS blockers and immunosuppression), with significantly greater reduction compared to placebo (odds ratio 0.65, p=0.002) 2
- Dapagliflozin (another SGLT2 inhibitor) reduced proteinuria by >30% in responders, with the proteinuria-lowering effect associated with an initial decline in eGFR—a hemodynamic effect indicating reduced intraglomerular pressure 3
- The proteinuria reduction was most pronounced in patients with baseline urinary protein-to-creatinine ratio ≥0.5 g/gCr 3
Important Clinical Considerations
Expected Initial eGFR Dip
- An initial decline in eGFR of approximately 6.5% within the first month is expected and represents a beneficial hemodynamic effect, not kidney injury 3
- This initial dip is actually associated with greater proteinuria reduction and long-term kidney protection 3
Monitoring Recommendations
- Assess proteinuria using spot urine albumin-to-creatinine ratio or protein-to-creatinine ratio 1, 4
- Monitor eGFR and albuminuria at least annually in patients with CKD, more frequently in those at higher risk of progression 5
- Confirm persistent proteinuria with 2 of 3 samples over 3 months to establish chronicity 4
Common Pitfalls to Avoid
- Do not discontinue empagliflozin due to initial eGFR decline—this is an expected hemodynamic effect that predicts long-term benefit 3
- Do not confuse the drug's mechanism with causing proteinuria—empagliflozin causes glucosuria (glucose in urine), not proteinuria 6
- Be aware of increased risk of mycotic genital infections, particularly in women, but this is unrelated to proteinuria 6
Rare Adverse Effect (Not Proteinuria)
The main metabolic concern with empagliflozin is euglycemic diabetic ketoacidosis, particularly during acute illness, decreased carbohydrate intake, or insulin dose reduction—not proteinuria 7
Clinical Bottom Line
Jardiance is renoprotective and should be considered as part of the treatment strategy for patients with diabetic kidney disease and proteinuria, not avoided due to concerns about causing proteinuria. The drug's ability to reduce proteinuria is one of its key therapeutic benefits for kidney protection. 1, 2