Systemic Autoimmune Diseases Research Unit, Internal Medicine Department, Vall d'Hebron Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Nephrol Dial Transplant. 2010 Dec;25(12):3939-48. doi: 10.1093/ndt/gfq322. Epub 2010 Jun 10.
Although mycophenolate mofetil (MMF) is being increasingly used to manage lupus nephritis (LN), long-term experience is limited. Despite treatment, a significant proportion of patients will be refractory to this regime.
We report, in this observational study, our long-term experience treating 70 patients with biopsy-proven LN, with MMF as continuous induction-maintenance therapy, who were followed up prospectively over a 5-year period. As rescue therapy for MMF-resistant cases, tacrolimus (0.075 mg/kg/day) was added. The study primary end point was complete response (CR). Secondary end points included partial response (PR), treatment failure, relapse and side effects. Predictor factors associated to renal outcome were analysed by Cox regression analysis.
Thirty-six MMF-treated patients (51%) remained in CR, and 23 (33%) failed treatment at last follow-up. Time to treatment failure was associated with persistent hypoalbuminaemia (hazard ratio (HR) = 0.87; 95%CI, 0.81-0.95; P = 0.001), higher proteinuria (HR = 1.29; 95%CI, 1.03-1.62; P = 0.030) and fewer early responses (HR 0.28; 95%CI, 0.10-0.77; P = 0.014). Renal relapse occurred in 24 (34%) patients. Time to flare was associated with persistent anti-dsDNA titres (HR = 1.001; 95%CI, 1.001-1.003; P = 0.005) and younger age at inclusion (HR = 0.36; 95%CI, 0.14-0.90; P = 0.029). Tacrolimus was added to 17 (24%) patients. A significant reduction of proteinuria was already observed at 3 months (P = 0.002). After 2 years follow-up, 12 (70%) of them achieved clinical response (six CR and six PR). Conclusions. MMF is an effective treatment for LN. Combination therapy with tacrolimus is an effective and safe alternative for MMF-resistant patients.
霉酚酸酯（MMF）越来越多地用于治疗狼疮肾炎（LN），但长期经验有限。尽管进行了治疗，但仍有相当一部分患者对此方案无反应。
在这项观察性研究中，我们报告了 70 例经活检证实的 LN 患者的长期经验，这些患者接受 MMF 作为连续诱导维持治疗，并在 5 年期间进行前瞻性随访。对于 MMF 耐药的病例，加用他克莫司（0.075mg/kg/天）作为挽救治疗。研究的主要终点是完全缓解（CR）。次要终点包括部分缓解（PR）、治疗失败、复发和副作用。通过 Cox 回归分析分析与肾脏结局相关的预测因素。
36 例接受 MMF 治疗的患者（51%）持续缓解，最后随访时有 23 例（33%）治疗失败。治疗失败的时间与持续低白蛋白血症（危险比[HR] = 0.87；95%置信区间，0.81-0.95；P = 0.001）、更高的蛋白尿（HR = 1.29；95%置信区间，1.03-1.62；P = 0.030）和较少的早期反应（HR 0.28；95%置信区间，0.10-0.77；P = 0.014）有关。24 例（34%）患者发生肾复发。复发时间与持续的抗 dsDNA 滴度（HR = 1.001；95%置信区间，1.001-1.003；P = 0.005）和纳入时的年龄较小（HR = 0.36；95%置信区间，0.14-0.90；P = 0.029）有关。17 例（24%）患者加用他克莫司。在 3 个月时已观察到蛋白尿显著减少（P = 0.002）。在 2 年随访时，其中 12 例（70%）患者达到临床缓解（6 例 CR 和 6 例 PR）。结论。MMF 是治疗 LN 的有效药物。他克莫司联合治疗是治疗 MMF 耐药患者的有效且安全的替代方法。
