Department of Nursing, Faculty of Health and Medical Care, Hachinohe Gakuin University, Hachinohe, Japan.
Department of School Health Science, Hirosaki University Faculty of Education, Hirosaki, Japan.
Nephrology (Carlton). 2024 Dec;29(12):901-908. doi: 10.1111/nep.14406. Epub 2024 Oct 21.
We have previously reported the mid-term efficacy and safety of tacrolimus (Tac)-based immunosuppressive therapy in such patients, and herein, we aimed to determine their long-term outcomes (over 10 years).
We retrospectively evaluate the data of 13 consecutive patients with biopsy-proven long-standing LN who underwent a long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as reinduction or maintenance treatment. Treatment outcomes were defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein/creatinine ratio (Up/cr), serum creatinine, estimated glomerular filtration rate (eGFR) and serological lupus markers (complement C3, complement hemolytic activity [CH 50], and anti-dsDNA antibody titre), and the concomitantly administered prednisolone (PDN) dose. Data on clinical parameters and serological lupus activity were collected annually from each patient throughout the study period.
The patients' baseline characteristics at the treatment initiation were as follows: mean age, 18 years; Up/cr, 0.63 ± 0.69; serum C3 level, 57.2 ± 22.4 mg/dL (normal range, 79-152 mg/dL); CH50, 27.9 ± 15.7 U/mL (normal range, 23.0-46.0 U/mL); serum anti-dsDNA antibody titre, 111.7 ± 123.4 IU/mL (normal range, <12.0 IU/mL); serum creatinine, 0.60 ± 0.19 mg/dL; eGFR, 115.6 ± 21.3 mL/min and SLEDAI, 13 ± 8.1. Despite the gradual tapering of the concomitantly administered PDN dose from 18.7 ± 13.5 mg/day at baseline to 3.5 ± 2.8 mg/day at 10 years (p = .002), a marked improvement in the outcomes, compared with the baseline values, was observed within a year. Additionally, these favourable changes persisted throughout study period in most patients. Compared with the baseline values, the following measures confirmed sustained outcome improvements after a 10-year treatment: SLEDAI, 1.7 ± 2.0; serum C3 level, 83.8 ± 16.1 mg/dL; CH50, 45.6 ± 10.9 U/mL (all p < .01) and Up/cr, 0.16 ± 0.18 and serum anti-dsDNA antibody titre, 25.8 ± 28.8 IU/mL (both p < .05). Serum creatinine level and eGFR remained within the normal range in all study participants except for one patient who experienced several flare-ups. No serious adverse effects were observed.
Our results suggest that long-term Tac-based immunosuppressive treatment as maintenance therapy is beneficial and has low cytotoxicity. Therefore, it represents an attractive option for the treatment of selected patients with paediatric-onset LN in a real-world setting.
我们之前报告了他克莫司（Tac）为基础的免疫抑制疗法在这类患者中的中期疗效和安全性，在此，我们旨在确定他们的长期结局（超过 10 年）。
我们回顾性评估了 13 例经活检证实的长期狼疮性肾炎患者的长期 Tac 治疗方案的数据。Tac 以 3mg 的剂量每日一次作为诱导或维持治疗。使用系统性红斑狼疮疾病活动指数（SLEDAI）、尿蛋白/肌酐比（Up/cr）、血清肌酐、估计肾小球滤过率（eGFR）和血清狼疮标志物（补体 C3、补体溶血活性[CH50]和抗 dsDNA 抗体滴度）来定义治疗结局，并同时给予泼尼松龙（PDN）剂量。在整个研究期间，每年从每位患者收集有关临床参数和血清狼疮活动的数据。
治疗开始时患者的基线特征如下：平均年龄 18 岁；Up/cr，0.63±0.69；血清 C3 水平，57.2±22.4mg/dL（正常值范围，79-152mg/dL）；CH50，27.9±15.7U/mL（正常值范围，23.0-46.0U/mL）；血清抗 dsDNA 抗体滴度，111.7±123.4IU/mL（正常值范围，<12.0IU/mL）；血清肌酐，0.60±0.19mg/dL；eGFR，115.6±21.3mL/min，SLEDAI，13±8.1。尽管同时给予的 PDN 剂量从基线时的 18.7±13.5mg/天逐渐减少到 10 年时的 3.5±2.8mg/天（p=0.002），但与基线值相比，在一年内观察到结果明显改善。此外，在大多数患者中，这些有利的变化在整个研究期间持续存在。与基线值相比，经过 10 年治疗后，以下措施证实了持续的结局改善：SLEDAI，1.7±2.0；血清 C3 水平，83.8±16.1mg/dL；CH50，45.6±10.9U/mL（均 p<0.01）和 Up/cr，0.16±0.18 和血清抗 dsDNA 抗体滴度，25.8±28.8IU/mL（均 p<0.05）。除了一名经历多次发作的患者外，所有研究参与者的血清肌酐水平和 eGFR 均保持在正常范围内。未观察到严重的不良反应。
我们的结果表明，作为维持治疗的长期 Tac 为基础的免疫抑制治疗是有益的，且具有低细胞毒性。因此，对于现实环境中选择的儿童发病狼疮性肾炎患者，它是一种有吸引力的治疗选择。
