Endothelin Receptor Antagonist Ambrisentan, Sodium-Glucose Cotransporter 2 Inhibitor Henagliflozin, and Their Combination in IgA Nephropathy: A Randomized Crossover Trial
Abstract
Key points: Proteinuria responses to endothelin receptor antagonists and sodium-glucose cotransporter 2 inhibitors were not correlated. Ambrisentan-henagliflozin combination therapy reduced proteinuria similarly to ambrisentan monotherapy but exceeded henagliflozin alone. Combination therapy resulted in markedly less fluid retention and weight gain compared with endothelin receptor antagonist monotherapy.
Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and endothelin receptor antagonists (ERAs) can reduce proteinuria and may slow kidney progression in IgA nephropathy. Their potential synergistic efficacy and safety are unclear.
Methods: This open-label randomized crossover trial enrolled adults with IgA nephropathy, eGFR >30 ml/min per 1.73 m 2 , and 24-hour urine protein-creatinine ratio (UPCR) ≥0.44 g/g or 24-hour urine protein ≥0.5 g, despite maximal renin-angiotensin system blockade. Treatments were given in random order (ambrisentan 5 mg/d, henagliflozin 10 mg/d, and combination), each for 4 weeks followed by a 4-week washout. Primary end point was correlation between treatments in 24-hour UPCR changes. Secondary end points included eGFR change. Safety end points included fluid retention (body weight change).
Results: Sixty-five patients were enrolled, with a mean baseline eGFR of 69 ml/min per 1.73 m 2 (SD=23) and a median 24-hour UPCR of 0.8 g/g (0.6-1.3). No correlation was found in 24-hour UPCR reduction between single-agent therapy and combination…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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