CMID-Nephrology and Dialysis Unit (ERK-Net Member), Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, University of Turin and San Giovanni Bosco Hospital, Piazza del Donatore di Sangue 3, 10054, Turin, Italy.
J Nephrol. 2021 Apr;34(2):565-571. doi: 10.1007/s40620-020-00781-6. Epub 2020 Jun 27.
Patients (pts) with primary Membranous nephropathy (MN) have an autoimmune disease caused by autoantibodies against podocyte antigens and 60-80% of them have antibodies directed against the M-type phospholipase A2 receptor (PLA2R). Immunosuppressive treatment is recommended in high-medium risk pts. Recently the use of rituximab (RTX), has emerged as an important therapeutic option in pts with primary MN. The appropriate cumulative dose of RTX in PMN pts is still uncertain, and favorable outcomes even with low-dose of RTX has been described. We compared efficacy and safety of 3 different treatment regimens: low-dose RTX (Protocol 1, one dose of RTX 375 mg/m), standard RTX protocol (Protocol 2, four weekly doses of rituximab 375 mg/m) and Ponticelli's regimen.
42 pts with primary MN and nephrotic syndrome were assigned to Protocol 1 (14 pts) or Protocol 2 (14 pts). All patients were followed for 24 months after RTX. Fourteen pts, matched for age and baseline serum creatinine (sCr) and proteinuria, treated with Ponticelli's regimen were examined as controls.
At 24 months, a significant improvement in proteinuria levels was observed in pts treated with Protocol 1 (7.5 ± 4.8 at T0; 0.21 ± 0.15 at T24, p < 0.01), Protocol 2 (5.1 ± 1.41 g/24 at T0; 0.35 ± 0.39 at T24 p < 0.01) and controls (8.27 ± 4.78 T0; 2.2 ± 1.9 g/24 h at T24, p < 0.01). No differences in clinical response (p = 0.53) was observed comparing the 3 groups.
Our data suggest that the RTX is a promising alternative to Ponticelli's regimen even at low-doses. This makes RTX a cost-effective treatment of primary MN in the short and medium terms.
原发性膜性肾病（PMN）患者患有自身免疫性疾病，由针对足细胞抗原的自身抗体引起，其中 60-80%的患者具有针对 M 型磷脂酶 A2 受体（PLA2R）的抗体。在中高危患者中推荐使用免疫抑制治疗。最近，利妥昔单抗（RTX）在原发性 MN 患者中的应用已成为一种重要的治疗选择。PMN 患者的 RTX 累积剂量尚不确定，甚至低剂量的 RTX 也有良好的效果。我们比较了 3 种不同治疗方案的疗效和安全性：低剂量 RTX（方案 1，1 次 RTX 375mg/m）、标准 RTX 方案（方案 2，4 周剂量 375mg/m 的利妥昔单抗）和 Ponticelli 方案。
42 例原发性 MN 伴肾病综合征患者被分配到方案 1（14 例）或方案 2（14 例）。所有患者在 RTX 后均随访 24 个月。14 例年龄和基线血肌酐（sCr）及蛋白尿匹配的患者接受 Ponticelli 方案治疗作为对照组。
在 24 个月时，方案 1（T0 时 7.5±4.8，T24 时 0.21±0.15，p<0.01）、方案 2（T0 时 5.1±1.41g/24，T24 时 0.35±0.39，p<0.01）和对照组（T0 时 8.27±4.78，T24 时 2.2±1.9g/24h，p<0.01）患者蛋白尿水平均显著改善。3 组间临床反应无差异（p=0.53）。
我们的数据表明，RTX 是 Ponticelli 方案的一种有前途的替代方案，即使在低剂量下也是如此。这使得 RTX 在短期和中期成为一种具有成本效益的原发性 MN 治疗方法。
