Prospective Cohort Study of Obinutuzumab in Rituximab-Resistant Primary Membranous Nephropathy

作者：Matias Trillini, V. Portalupi, A. Gennarini, Livia Surdi, Annachiara Currado, M. Marasà, M. A. Podestà, A. Villa, T. Peracchi, Diego Fidone, N. Rubis, Olimpia Diadei, Chiara Guarinoni, F. Casiraghi, M. Todeschini, D. Cugini, Fabiola Carrara, D. Martinetti, Paola Rizzo, G. Remuzzi, P. Ruggenenti · 发表于：Kidney International Reports · 年份：2025 · DOI：10.1016/j.ekir.2025.103728 · 被引用次数：8 · 研究领域：Medicine

Introduction Approximately 30% of patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome (NS) fail rituximab therapy through mechanisms that could be overcome by obinutuzumab. Methods In this prospective, single-arm, single-center, open-label trial, 20 consenting adults with MN and rituximab-resistant NS received three 1000 mg obinutuzumab infusions at the Bergamo Nephrology Unit (Italy) between March 2022 and February 2024 and were monitored for ≤ 12 months. The primary outcome was a composite end point of normo-albuminemia and complete (proteinuria < 0.3 g/d) or partial (proteinuria < 3.5 g/d with ≥ 50% reduction from baseline) NS remission at 12-month follow-up. Twenty-four-hour proteinuria and glomerular filtration rate (GFR) were evaluated at baseline and at 3, 6, 9, 12, 18, and 24 months posttreatment. Results At 12 months, 16 patients met the combined end point, 4 with complete remission. No patient relapsed after remission. Median (interquartile range) 24-h proteinuria decreased from 5.7 (4.7–8.1) to 1.3 (0.5–2.7) g/24 h. Albumin and IgG fractional clearances also decreased, whereas serum albumin increased from 2.9 ± 0.6 g/dl to 3.9 ± 0.3 g/dl (P < 0.0001 for all changes). Dyslipidemia, hypocalcemia, and hypo-gammaglobulinemia improved significantly and GFR stabilized. At 12 months, total B cells and circulating anti–phospholipase A2 receptor (PLA2R) antibodies were depleted. Similar findings were observed in the cohort of 10 patients who ...