Abstract
Background:Patients with paroxysmal nocturnal hemoglobinuria (PNH) experience chronic intravascular hemolysis due to the deficiency of complement regulatory proteins. The released free hemoglobin induces kidney injury through hemosiderin deposition, inflammation, and nitric oxide (NO) depletion, which inducing renal failure being one of the leading causes of mortality. Some researchers have reported that eculizumab can effectively improve renal function in patients with PNH. However, there have been no reports on the impact of iptacopan on renal function in patients with PNH.Aims:This study presents the real world's comparative analysis of iptacopan and eculizumab in improving renal function in PNH patients.Methods:A prospective observational registry including 18 PNH patients treated with iptacopan and 13 patients treated with eculizumab was coducted from September 2024 to June 2025. The staging of chronic kidney disease (CKD) is used to assess the severity of a patient's renal insufficiency or impairment.Results:Among the 31 PNH patients we followed up, renal impairment at baseline was observed in 14 out of 18 (78%) patients treated with iptacopan (including 6 patients with CKD stage 2–3 and 8 with CKD stage 1) and in all 13 patients receiving eculizumab (including 2 with CKD stage 4, 5 with CKD stage 3, 5 with CKD stage 2, and 1 with CKD stage 1).After a median treatment duration of 8 weeks (range: 4–36 weeks) with iptacopan, renal function improved in 4 patients. Notably, 3 out of 6 (50%) patients with CKD stage 2–3 showed improvement to CKD stage 1 (median eGFR increase: 14.4 mL/min/1.73 m²), while 1 patient with CKD stage 1 achieved normal renal function. Similarly, following a median treatment duration of 24 weeks (range: 4–48 weeks) with eculizumab, 4 patients showed renal function improvement (median eGFR increase: 24.5 mL/min/1.73 m²), whereas 2 experienced deterioration (median eGFR decrease: 17.25 mL/min/1.73 m²).Kaplan-Meier curve analysis was performed on patients with renal impairment at baseline to assess cumulative response rates. After 8 weeks of treatment, the cumulative response rate was 22.6% in the iptacopan group compared to 15.4% in the eculizumab group. By week 24, the cumulative response rate had risen to 48.4% for iptacopan-treated patients versus 27.5% for those receiving eculizumab.
Conclusion:Both eculizumab and iptacopan have been shown to improve renal function in patients with PNH.
