Katsuno Takayuki, Ozaki Takenori, Ozeki Takaya, Hachiya Asaka, Kim Hangsoo, Kato Noritoshi, Ishimoto Takuji, Kato Sawako, Kosugi Tomoki, Tsuboi Naotake, Mizuno Masashi, Ito Yasuhiko, Maruyama Shoichi
Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan.
Clin Exp Nephrol. 2018 Dec;22(6):1341-1350. doi: 10.1007/s10157-018-1590-2. Epub 2018 May 23.
Mycophenolate mofetil (MMF) is recommended as a first-line immunosuppressant to treat lupus nephritis (LN). Prognosis and therapeutic response in LN are known to vary depending on race. We investigated the benefits of MMF and therapeutic drug monitoring (TDM) in the treatment of Japanese LN patients.
In this retrospective cohort study, a total of 20 patients with LN who started MMF treatment were included. Clinical data were collected regularly after MMF administration. We evaluated complete remission (CR) rate as the primary outcome. Predictors of CR were identified using univariate and multivariate analyses. In the research of TDM, the correlation with the area under the curve (AUC) was analyzed at MMF dose, single-point value, treatment response, and adverse events.
Overall, 70% of cases showed CR; both flare-ups and refractory cases had favorable results. Cases of LN with nephrotic syndrome (NS) or class III/IV + V showed a significantly lower CR rate (p < 0.005). The ratio of maintaining CR after MMF therapy was as high as 85.7%. In multivariate analysis, NS was an independent negative predictor of CR (HR 0.09, 95% confidence interval 0.01-0.81; p = 0.03). The relationship between AUC and MMF dose was low, and AUC correlated with trough level (r = 0.73). AUC tended to be high in the treatment responder (p = 0.09), but did not correlate with adverse events of infection (p = 0.92).
MMF is a beneficial treatment option for Japanese LN patients, and further investigation on TDM-based therapy is needed.
霉酚酸酯（MMF）被推荐作为治疗狼疮性肾炎（LN）的一线免疫抑制剂。已知LN的预后和治疗反应因种族而异。我们研究了MMF和治疗药物监测（TDM）在治疗日本LN患者中的益处。
在这项回顾性队列研究中，纳入了总共20例开始MMF治疗的LN患者。MMF给药后定期收集临床数据。我们将完全缓解（CR）率作为主要结局进行评估。使用单变量和多变量分析确定CR的预测因素。在TDM研究中，分析了MMF剂量、单点值、治疗反应和不良事件与曲线下面积（AUC）的相关性。
总体而言，70%的病例显示CR；复发和难治性病例均有良好结果。伴有肾病综合征（NS）或III/IV+V级的LN病例CR率显著较低（p<0.005）。MMF治疗后维持CR的比例高达85.7%。在多变量分析中，NS是CR的独立负性预测因素（HR 0.09，95%置信区间0.01-0.81；p=0.03）。AUC与MMF剂量之间的关系较弱，且AUC与谷浓度相关（r=0.73）。治疗反应者的AUC往往较高（p=0.09），但与感染不良事件无关（p=0.92）。
MMF是日本LN患者的有益治疗选择，需要对基于TDM的治疗进行进一步研究。
