脉冲式静脉注射甲泼尼龙联合小剂量泼尼松治疗高危 IgA 肾病：一项为期 18 个月的前瞻性临床试验。

Effect of pulsed intravenous methylprednisolone with alternative low-dose prednisone on high-risk IgA nephropathy: a 18-month prospective clinical trial.

机构信息

Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Fifth Road, Xi'an, 710004, Shaanxi, China.

School of Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.

出版信息

Sci Rep. 2022 Jan 7;12(1):255. doi: 10.1038/s41598-021-03691-0.

Full-dose prednisone (FP) regimen in the treatment of high-risk immunoglobulin A nephropathy (IgAN) patients, is still controversial. The pulsed intravenous methylprednisolone combined with alternative low-dose prednisone (MCALP) might have a more favorable safety profile, which has not been fully investigated. Eighty-seven biopsy-proven IgAN adult patients and proteinuria between 1 and 3.5 g/24 h after ACEI/ARB for at least 90 days were randomly assigned to 6-month therapy: (1) MCALP group: 0.5 g of methylprednisolone intravenously for three consecutive days at the beginning of the course and 3rd month respectively, oral prednisone at a dose of 15 mg every other day for 6 months. (2) FP group: 0.8-1.0 mg/kg/days of prednisone (maximum 70 mg/day) for 2 months, then tapered by 5 mg every 10 days for the next 4 months. All patients were followed up for another 12 months. The primary outcome was complete remission (CR) of proteinuria at 12 months. The percentage of CR at 12th and 18th month were similar in the MCALP and FP groups (51% vs 58%, P = 0.490, at 12th month; 60% vs 56%, P = 0.714, at 18th month). The cumulative dosages of glucocorticoid were less in the MCALP group than FP group (4.31 ± 0.26 g vs 7.34 ± 1.21 g, P < 0.001). The analysis of the correlation between kidney biopsy Oxford MEST-C scores with clinical outcomes indicated the percentages of total remission was similar between two groups with or without M1, E1, S1, T1/T2, and C1/C2. More patients in the FP group presented infections (8% in MCALP vs 21% in FP), weight gain (4% in MCALP vs 19% in FP) and Cushing syndrome (3% in MCALP vs 18% in FP). These data indicated that MCALP maybe one of the choices for IgAN patients with a high risk for progression into ESKD.Trial registration: The study approved by the Chinese Clinical Trial Registry (registration date 13/01/2018, approval number ChiCTR1800014442, https://www.chictr.org.cn/ ).

在治疗高危免疫球蛋白 A 肾病 (IgAN) 患者时，使用全剂量泼尼松 (FP) 方案仍存在争议。脉冲式静脉内甲泼尼龙联合交替低剂量泼尼松 (MCALP) 可能具有更好的安全性，但尚未得到充分研究。

本研究纳入了 87 名经活检证实的 IgAN 成年患者，这些患者在使用血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂 (ACEI/ARB) 至少 90 天后，蛋白尿水平为 1 至 3.5 g/24 h。患者被随机分配接受 6 个月的治疗：(1) MCALP 组：在疗程开始时和第 3 个月分别静脉内给予 0.5 g 甲泼尼龙，连续 3 天，同时口服泼尼松，剂量为 15 mg，隔天 1 次，持续 6 个月。(2) FP 组：泼尼松剂量为 0.8-1.0 mg/kg/天（最大剂量 70 mg/天），持续 2 个月，然后在接下来的 4 个月中每 10 天减少 5 mg。所有患者均随访 12 个月。主要结局是治疗 12 个月时蛋白尿完全缓解 (CR)。在 MCALP 组和 FP 组中，第 12 个月和第 18 个月时 CR 的百分比相似（第 12 个月时分别为 51%和 58%，P=0.490；第 18 个月时分别为 60%和 56%，P=0.714）。MCALP 组的糖皮质激素累积剂量低于 FP 组（4.31±0.26 g 比 7.34±1.21 g，P<0.001）。

对肾脏活检牛津 MEST-C 评分与临床结局的相关性分析表明，两组的完全缓解率相似，无论是在有 M1、E1、S1、T1/T2 和 C1/C2 还是无 M1、E1、S1、T1/T2 和 C1/C2 的患者中。FP 组更多的患者出现感染（MCALP 组为 8%，FP 组为 21%）、体重增加（MCALP 组为 4%，FP 组为 19%）和库欣综合征（MCALP 组为 3%，FP 组为 18%）。这些数据表明，MCALP 可能是 IgAN 患者进展为终末期肾病高危因素的一种选择。