Protective Effect of Ambrisentan on Proteinuria in Patients with Alport Syndrome

Background: In recent years, endothelin receptor antagonists (ERAs) have stepped into the spotlight of chronic kidney disease treatment, showing a significant reduction in proteinuria and preservation of kidney function, such as SONAR study in diabetic nephropathy, DUPLEX trial in focal segmental glomerulosclerosis (FSGS) and PROTECT trial in IgA nephropathy. However, whether they are effective in Alport syndrome (AS) is unclear. Methods: This was a real-world study. AS patients that had been treated with RAASi or RAASi combined with sodium-dependent glucose transporters 2 inhibitors (SGLT2i) / mineralocorticoid receptor (MRA) in stable doses for at least 3 months but still with proteiuria (＞0.5g/d）and eGFR＞25 ml/min/1.73m2 were included. All of them received ambrisentan 5 mg daily. Efficacy was assessed by the changes in proteinuria. The safety outcomes included renal function change and tolerance. Results: In total, 12 patients with AS were included. The mean baseline 24-hour urinary protein (UTP) (±SD) was 2.73 ± 1.56g/d and decreased to 2.14 ± 1.32g/d after two-month treatment (P=0.001). The mean eGFR was stable in the two months (mean 57.08 vs. 58.98 ml/min/1.73m2 at baseline). 2 patients discontinued due to edema and 2 due to headache in the second month. Other patients never reported any side effects. Among the patients, four have been followed over 6 months with additional 4 months follow-up data. We observed a continued decrease trend in urinary protein, additional 20.85±10.67% from the second month in the UTP reduction, and 36.61±16.06% reduction from the baseline. The eGFR remained stable. Conclusion: The pilot study suggests that introducing of ERA on top of RAASi with or without SGLT2i/MRA provides an additional antiproteinuric effect in AS.