What is the average decrease in Urine Protein-to-Creatinine Ratio (UPCR) for patients with IgA nephropathy taking Sodium-Glucose Cotransporter 2 (SGLT2) medications?

SGLT2 Inhibitors Reduce UPCR by 34-62% in IgA Nephropathy Patients

SGLT2 inhibitors reduce urine protein-to-creatinine ratio (UPCR) by approximately 34-62% in patients with IgA nephropathy, with the most recent evidence showing a 62% reduction after 14 weeks of treatment. 1

Mechanism and Evidence for SGLT2 Inhibitors in IgA Nephropathy

SGLT2 inhibitors have emerged as an important non-immunosuppressive treatment option for patients with IgA nephropathy. Their renoprotective effects extend beyond glycemic control and include:

• Reduction in intraglomerular pressure
• Anti-inflammatory effects
• Decreased albuminuria/proteinuria
• Slowing of kidney disease progression

Specific Evidence on UPCR Reduction

The most recent clinical evidence demonstrates significant proteinuria reduction with SGLT2 inhibitors in IgA nephropathy:

• A 2025 real-world study showed SGLT2 inhibitors contributed to a 62% reduction in UPCR after 14 weeks of treatment in IgA nephropathy patients 1
• In another study, targeted-release budesonide showed a 34% reduction in proteinuria from baseline at 9 months in IgA nephropathy patients 2

Treatment Algorithm for IgA Nephropathy

1. First-line therapy:

   • ACE inhibitors or ARBs titrated to maximum tolerated dose for patients with proteinuria 2, 3
   • These agents reduce proteinuria by approximately 0.71-1.16 g/24h compared to placebo or symptomatic treatment 3

2. Add SGLT2 inhibitor:

   • For patients with eGFR ≥20 mL/min/1.73 m² 2
   • Expected UPCR reduction: 34-62% 2, 1
   • Can be continued at lower levels of eGFR once initiated 2

3. Consider additional therapies for persistent proteinuria:

   • GLP-1 receptor agonists (especially for diabetic patients) 4
   • Nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs) for patients with eGFR ≥25 mL/min/1.73 m² and normal potassium 2
   • Endothelin receptor antagonists (e.g., atrasentan showed 38.1% reduction in UPCR) 5

Clinical Considerations and Monitoring

• Initial eGFR dip: SGLT2 inhibitors typically cause an initial 3-5 mL/min/1.73 m² decrease in eGFR that stabilizes over time 2
• Target UPCR reduction: Aim for at least 25% reduction by 3 months, 50% by 6 months, and UPCR below 500-700 mg/g by 12 months 2
• Monitoring parameters:
  • eGFR and UPCR at baseline and follow-up visits
  • Blood pressure (target <130/80 mmHg)
  • Potassium levels, especially if combining with RAS inhibitors

Potential Adverse Effects of SGLT2 Inhibitors

• Volume depletion/hypovolemia (due to diuretic action)
• Genital mycotic infections
• Euglycemic diabetic ketoacidosis (rare)
• Discontinue 3-4 days before elective procedures 2

Summary

SGLT2 inhibitors provide significant proteinuria reduction in IgA nephropathy patients, with recent evidence showing a 34-62% decrease in UPCR. This reduction is clinically meaningful as proteinuria is a strong predictor of disease progression in IgA nephropathy. The combination of ACE inhibitors/ARBs with SGLT2 inhibitors appears to offer additive benefits for proteinuria reduction and kidney protection.