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April 10, 2026Journal of the American Society of Nephrology

Endothelin Receptor Antagonist Ambrisentan, SGLT2 Inhibitor Henagliflozin, and Their Combination in IgA Nephropathy

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Authors

QCQinlan ChenPCPei ChenLLLijun Liu

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Overview

Open-label trial investigates proteinuria reduction in IgA nephropathy via combination therapy, indicating efficacy benefits.

Key Points

  • The study aims to evaluate the efficacy and safety of the endothelin receptor antagonist ambrisentan and the SGLT2 inhibitor henagliflozin alone and in combination in patients with IgA nephropathy.
  • Conducted an open-label randomized crossover trial.
  • Enrolled adults with IgA nephropathy and specific criteria for kidney function and protein levels.
  • Administered treatments in random order: ambrisentan, henagliflozin, and combination for 4 weeks each, with a 4-week washout period.
  • Primary endpoint assessed changes in 24-hour urine protein-creatinine ratio (UPCR).
  • Secondary endpoints evaluated changes in eGFR and safety indicators.
  • Sixty-five patients were included, with a mean baseline eGFR of 69 ml/min/1.73 m2 and median 24-hour UPCR of 0.8 g/g.
  • Combination therapy resulted in a -44% reduction in 24-hour UPCR, superior to henagliflozin alone (-21%), but similar to ambrisentan (-48%).
  • Mean change in eGFR was -4.7 ml/min/1.73 m2 for combination therapy, significantly greater than ambrisentan (-0.5 ml/min/1.73 m2), but comparable to henagliflozin (-3.5 ml/min/1.73 m2).
  • Combination treatment led to less fluid retention compared to ambrisentan alone.

Cite This Study

Chen et al. (2026) studied this question.

synapsesocial.com/papers/69d8962d6c1944d70ce07743https://doi.org/10.1681/asn.0000001097
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Ambrisentan as adjunctive therapy for IgA nephropathy: a retrospective single-center analysis2026
  2. 2#1679 Relationship between initial eGFR DIP with proteinuria after SGLT2i treatment, in patients with IgA nephropathy. A real-world clinical study2024 · 1 citations
  3. 3Additive Antiproteinuric Effect of Combination Therapy with ACE Inhibitor and Angiotensin II Receptor Antagonist: Differential Short-term Response between IgA Nephropathy and Diabetic Nephropathy2003 · 31 citations
  4. 4Efficacy and safety of agents for IgA nephropathy: a network meta-analysis of randomized controlled trials2025 · 4 citations
  5. 5Initial effect of sodium-glucose cotransporter-2 inhibitors on kidney function in patients with immunoglobulin A nephropathy2026