Ambrisentan as adjunctive therapy for IgA nephropathy: a retrospective single-center analysis

BACKGROUND: Proteinuria and hematuria are both significant predictors of impaired kidney function in IgA nephropathy (IgAN). We evaluated the efficacy and safety of ambrisentan, a selective endothelin A receptor antagonist, as adjunctive therapy in a real-world cohort of high-risk IgAN patients. METHODS: In this retrospective, single-center study, we analyzed 169 patients with biopsy-proven IgAN who received adjunctive ambrisentan for ≥6 months. A propensity score-matched historical control group (138 pairs) was generated from patients receiving standard care prior to the ambrisentan era. Laboratory test results were gathered at baseline, and at 3 and 6 months. A generalized estimating equation model was employed to adjust for potential confounders. RESULTS: In the full ambrisentan cohort (n = 169), median urinary protein-to-creatinine ratio (UPCR) decreased significantly by 58.4% (95% confidence interval [CI], 49.8-62.3) at 6 months, with 75.7% of patients achieving a ≥30% reduction. Hematuria was also significantly reduced (P < .001), and kidney function remained stable. Compared to the matched controls, the ambrisentan group (n = 138 after propensity score-matching) demonstrated a greater median relative reduction in UPCR (-59.7% vs. -53.7%; P = .015). However, a decrease in hemoglobin levels was observed, with an increased incidence of anemia. The proteinuria-lowering effect was enhanced in patients concurrently receiving angiotensin converting enzyme inhibitors (ACEi)/ angiotensin receptor blockers (ARBs) or finerenone. CONCLUSIONS: In this analysis incorporating a matched historical control, adjunctive ambrisentan significantly reduced proteinuria and hematuria in patients with IgAN without affecting kidney function. The proteinuria-lowering effect was more pronounced when ambrisentan was added to an ACEi/ARB or finerenone. Notably, a significant decline in hemoglobin levels was observed, indicating a need for monitoring. These results warrant further prospective trials to confirm the long-term renal benefits and safety of ambrisentan in IgAN.