Ueda Satoshi, Sugimoto Keisuke, Yanagida Hidehiko, Fujita Shinsuke, Miyazawa Tomoki, Sakata Naoki, Okada Mitsuru, Takemura Tsukasa
Department of Pediatrics, Kinki University School of Medicine, Osaka, Japan.
Ther Apher Dial. 2011 Oct;15(5):499-503. doi: 10.1111/j.1744-9987.2011.00984.x. Epub 2011 Jun 9.
In two patients with steroid-resistant nephrotic syndrome (SRNS), we investigated the relationship between clinical findings during immunosuppressive therapy and multiple drug resistant gene-1 (MDR-1) expression. MDR-1 was detected by real-time polymerase chain reaction (PCR). In a boy who initially developed SRNS at 3years, we observed MDR-1 expression over 3years. Maximal and minimal MDR-1 expression were 90,000 and 7800 copies/µg RNA, respectively. In a 4-year-old boy who initially developed SRNS at 3years, we determined MDR-1 expression over 2years. Maximal and minimal MDR-1 expression were 42,000 and 6900, respectively. MDR-1 evaluation requires determination of MDR-1 expression at several time points in a clinical course. Establishment of a normal expression may be needed for each individual patient. Increasing MDR-1 during remission was followed soon by recurrences, an observation that may be a guide for therapeutic choice. LDL influences a humoral factor involved in MDR-1 expression. Both patients responded to LDL adsorption therapy because of elevated LDL levels. While cyclosporine A therapy gradually decreased MDR-1 expression, LDL adsorption therapy decreased expression sharply. Based on the results of the present study, LDL adsorption therapy could contribute to the amelioration of drug sensitivity for immunosuppressants including corticosteroids via inhibitory effects on MDR-1 expression.
在两名激素抵抗型肾病综合征（SRNS）患者中，我们研究了免疫抑制治疗期间的临床发现与多药耐药基因1（MDR-1）表达之间的关系。通过实时聚合酶链反应（PCR）检测MDR-1。在一名3岁时最初患上SRNS的男孩中，我们观察了其3年期间的MDR-1表达情况。MDR-1的最大和最小表达量分别为90,000和7800拷贝/微克RNA。在一名3岁时最初患上SRNS的4岁男孩中，我们测定了其2年期间的MDR-1表达情况。MDR-1的最大和最小表达量分别为42,000和6900。对MDR-1的评估需要在临床过程中的多个时间点测定其表达情况。可能需要为每个患者确定正常表达水平。缓解期MDR-1升高后很快就会复发，这一观察结果可能为治疗选择提供指导。低密度脂蛋白（LDL）影响参与MDR-1表达的一种体液因子。由于LDL水平升高，两名患者均对LDL吸附疗法有反应。虽然环孢素A治疗使MDR-1表达逐渐降低，但LDL吸附疗法使表达急剧下降。根据本研究结果，LDL吸附疗法可能通过对MDR-1表达的抑制作用，有助于改善包括皮质类固醇在内的免疫抑制剂的药物敏感性。
