Schanz Moritz, Seikrit Claudia, Hohenstein Bernd, Zimmermann Aline, Kraft Leonie, Schricker Severin, Berger Susann, Schwab Andrea, Oberacker Tina, Latus Joerg
Department of General Internal Medicine and Nephrology, Robert Bosch Hospital Stuttgart, Stuttgart, Germany.
Division of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany.
Clin Kidney J. 2024 Dec 3;18(1):sfae394. doi: 10.1093/ckj/sfae394. eCollection 2025 Jan.
Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.
A total of 23 patients with IgAN were treated with sparsentan via the Managed Access Programme between December 2023 and August 2024. The patients were stable on maximum tolerated doses of renin-angiotensin system (RAS) and SGLT2 inhibitors, with an estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m² and a urine protein/creatinine ratio (UPCR) >0.75 g/g.
In the 23 patients, median (IQR) baseline eGFR (CKD-EPI) was 42 mL/min/1.73 m (32-63) and median baseline UPCR was 1.5 g/g (0.9-1.8). After initiation of sparsentan, UPCR significantly decreased ( < 0.0001) to a median of 0.85 g/g (0.42-1.15) in the 2-week follow-up and further declined ( = 0.001) to a median of 0.60 g/g (0.32-0.82) after 14 weeks, equivalent to a relative reduction in proteinuria up to 62% (45-74). A similar significant reduction was observed for the urine albumin/creatinine ratio. No drug-related serious adverse events were reported.
In this real-world setting, sparsentan shows a significant impact on proteinuria, leading to a relative reduction of 62% in UPCR after 14 weeks and beyond, even in patients already receiving SGLT2 inhibitors.
司帕生坦是一种血管紧张素II 1型受体和内皮素A受体的双重作用拮抗剂，已成为治疗IgA肾病（IgAN）的一种有前景的治疗药物。在PROTECT试验结果发表后，司帕生坦最近在欧洲获得了治疗IgA肾病的批准。然而，鉴于PROTECT研究未调查这种双重治疗方法，在已使用钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂进行现有治疗的背景下，是否能观察到相加效应仍不确定。
2023年12月至2024年8月期间，共有23例IgA肾病患者通过管理式准入计划接受司帕生坦治疗。这些患者在肾素-血管紧张素系统（RAS）和SGLT2抑制剂的最大耐受剂量下病情稳定，估计肾小球滤过率（eGFR）>30 mL/min/1.73 m²，尿蛋白/肌酐比值（UPCR）>0.75 g/g。
在这23例患者中，基线eGFR（CKD-EPI）的中位数（IQR）为42 mL/min/1.73 m²（32-63），基线UPCR的中位数为1.5 g/g（0.9-1.8）。开始使用司帕生坦后，UPCR在2周随访时显著降低（P<0.0001）至中位数0.85 g/g（0.42-1.15），并在14周后进一步下降（P=0.001）至中位数0.60 g/g（0.32-0.82），相当于蛋白尿相对减少高达62%（45-74）。尿白蛋白/肌酐比值也观察到类似的显著降低。未报告与药物相关的严重不良事件。
在这种现实世界环境中，司帕生坦对蛋白尿有显著影响，即使在已经接受SGLT2抑制剂治疗的患者中，14周及以后UPCR相对降低62%。
