随机对照试验研究泼尼松龙和多西环素在病因不明的急性间质性肾炎患者中的应用。
Randomized control trial of prednisolone and doxycycline in patients with acute interstitial nephritis of unknown aetiology.
机构信息
Centre for Education Research and Training On Kidney Diseases (CERTKiD), Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.
Department of Pathology, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.
出版信息
Trials. 2023 Jan 5;24(1):11. doi: 10.1186/s13063-022-07056-4.
BACKGROUND
Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology.
METHOD
A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients' presenting renal function to eGFR categories: 61-90 ml/min/1.73m (complete remission- CR) to 31-60 ml/min/1.73m (partial remission- PR) and 0-30 ml/min/1.73m no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching < 30 ml/min/1.73m eGFR), by 6-36 months. Analysis was by intention to treat.
RESULTS
Seventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D (p = 0.2), B vs. D (p = 0.1) and C vs. D (p = 0.4). In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found (p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%).
CONCLUSION
Prednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching < 30 ml/min/1.73m eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology.
TRIAL REGISTRATION
Sri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.
背景
斯里兰卡的医生曾用口服泼尼松龙和多西环素治疗病因不明的急性间质性肾炎（AIN）患者，这些患者可能是病因不明的慢性肾脏病（CKDu）最早的表现。本试验评估了泼尼松龙和多西环素对病因不明的 AIN 患者在 6 个月时 eGFR 变化的疗效。
方法
对病因不明的 AIN 患者（n=59）进行了一项随机临床试验，采用 2×2 析因设计，比较以下治疗方法：A-泼尼松龙、B-多西环素、C-两者联合治疗和 D-两者均不治疗。主要结局是患者的肾功能恢复到 eGFR 类别：61-90ml/min/1.73m（完全缓解-CR）至 31-60ml/min/1.73m（部分缓解-PR）和 0-30ml/min/1.73m（无缓解-NR）在 6 个月时。次要结局是在 6-36 个月时未达到<30ml/min/1.73m 的 eGFR 的无进展生存率。分析为意向治疗。
结果
共有 70 名符合 AIN 临床诊断的患者接受了活检以确定其是否符合入组条件；59 名病因不明的 AIN 患者被纳入研究，A 组=15，B 组=15，C 组=14，D 组=15 被随机分配到各个组。各组之间的基线特征相似。在 6 个月时，分别有 CR、PR 和 NR 的患者数在 A 组分别为 3：8：2，B 组分别为 2：8：3，C 组分别为 8：5：0，而 D 组分别为 8：6：1。A 组与 D 组（p=0.2）、B 组与 D 组（p=0.1）和 C 组与 D 组（p=0.4）之间未见显著差异。在一项探索性分析中，泼尼松龙治疗组（A+C）的无进展生存率为 0/29（100%），而未接受泼尼松龙治疗的（B+D）组为 25/30（83%），对数秩检验的 p 值为 0.02，而在接受多西环素治疗的（B+C）组（93%）和未接受多西环素治疗的（A+D）组（90%）之间未发现差异（p=0.60）。
结论
泼尼松龙和多西环素在 6 个月时对 CKDu 的最早表现没有益处。然而，泼尼松龙对 CKDu 的长期预后可能有一定的益处。需要一项足够大的、以病因不明的 AIN 患者在 3 年内达到<30ml/min/1.73m eGFR 为结局的类固醇试验。
试验注册
斯里兰卡临床试验注册处 SLCTR/2014/007，于 2014 年 3 月 31 日注册。
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