血管紧张素转换酶抑制剂治疗Alport综合征的临床分析

Clinical analysis of angiotensin - converting enzyme inhibitor in treatment of Alport syndrome

目的探讨血管紧张素转化酶抑制剂（ACEI）及血管紧张素受体阻滞剂（ARB）治疗儿童Alport综合征（As）的临床疗效及安全性。方法选取2013年1月至2017年12月在广州市第一人民医院儿科和深圳市人民医院儿科门诊或住院部确诊为AS的患儿共22例，其中4例未规律服药，不纳入本研究，共18例纳入本研究。18例患儿开始均接受ACEI治疗，观察时间为1-5年，若症状未有效控制，则改为ACEI联合ARB治疗，观察时间为1-3年。收集其临床资料和实验室检查结果[包括24h尿蛋白定量（mg／24h）、尿红细胞计数、血浆清蛋白（A11））、尿素氮（BUN）、血肌酐（Scr）、总胆固醇（TC）]。结果18例患儿开始治疗均使用ACEI类药物（福辛普利），治疗2年内，患儿尿蛋白和尿红细胞分别较前下降至47．7％和41．3％，治疗前后差异均有统计学意义（均P〈0．05），肾功能稳定在正常范围；2年后7例患儿先后出现尿蛋白及尿红细胞上升，肾功能下降，予ACEI联合ARB药物（氯沙坦）治疗，其余患儿在第3、4、5年尿蛋白及尿红细胞无明显变化，肾功能稳定。单独使用ACEI治疗5年，患儿尿蛋白下降至治疗前的47．8％，治疗前后差异有统计学意义（P〈0．05）；尿红细胞下降至治疗前的32．0％，治疗前后差异有统计学意义（P〈0．05）。7例患儿单用ACEI疗效不佳，改用ACEI联合ARB药物治疗后，第1年患儿尿蛋白及尿红细胞较前下降，肾功能好转，在第2、3年尿蛋白及尿红细胞无明显变化，肾功能稳定。ACEI联合ARB治疗3年，患儿尿蛋白下降至治疗前的42．3％，治疗前后差异有统计学意义（P〈0．05）；尿红细胞下降至治疗前的46．9％，治疗前后差异有统计学意义（P〈0．05）。结论ACEI治疗儿童AS可减轻尿蛋白，有助于延缓肾衰竭，对ACEI治疗效果不佳的患儿，采用ACEI联合ARB治疗，具有一定疗效，ARB可作为单用ACEI疗效不佳的AS的一种辅助手段。

Objective To investigate the clinical efficacy and safety of angiotensin - converting enzyme inhibitor （ACEI） and angiotensin receptor blocker （ARB） in treatment of children with Alport syndrome （AS）. Methods A total of 22 children with AS in Department of Pediatrics, Guangzhou First People＇s Hospital and Department of Pediatrics, Shenzhen People＇s Hospital between January 2013 and December 2017 were selected. But four children were not included in this study since they did not take medication regularly, and the other 18 cases were included in this study. All the 18 children were initially treated with ACEI. The observation time was from 1 to 5 years. If the symptoms were not effective- ly controlled,treatment plan would be changed to ACEI combined with ARB treatment. The observation time was from 1 to 3 years. The clinical data and laboratory examination results[ including 24 -hour urine protein （ mg/24 h） ,urine red blood cell count, plasma albumin （Alb） , urea nitrogen （BUN） , serum creatinine （Scr） , total cholesterol （ TC ） ] were collected for retrospective analysis. Results Eighteen patients started their treatment with ACEI inhibitors （ Fosinopril）. Within 2 years of treatment,the urinary protein and urinary red blood cells in the children decreased to 47.7% and 41.3% , respectively, and the differences were all statistically significant （ all P 〈0.05 ） , and the renal function was stable within the normal range. Two years later,7 patients had elevation of urinary protein and urinary erythrocyte eleva- tions and decrease of renal function,and they were treated with ACEI and ARB （Losartan）. The other children had no significant change in urine protein and urine red blood cells in the 3ra ,4th ,and 5＇h year,and their renal function was sta- ble. After ACEI treatment alone for 5 years,urinary protein was 47.8% lower than before treatment,and the difference was statistically significant （ P 〈 0. 05 ） ; urinary red blood cells decreased to 32.0% compared with before treatment, and the difference was statistically significant （ P 〈 0.05 ）. Seven patients with ACEI alone had poor efficacy, after the treatment with ACEI combined with ARB, the urinary protein and urine red blood cells were lower in the first year and the renal function improved. There was no significant change in urinary protein and urine red blood cells in the 2^nd and 3^nd year,and renal function was stable. After ACEI combined with ARB treatment for 3 years, urinary protein decreased to 42.3% before treatment, and the difference was statistically significant （P 〈 0. 05）, and urinary red blood cells decreased to 46.9% compared with before treatment, and the difference was statistically significant （ P 〈 0. 05 ）. Conclusions ACEI treatment of children with AS can reduce urine protein and help delay renal failure. For children with poor efficacy of ACEI treatment,ACEI combined with ARB may have a certain effect. ARB can be used as an adjunctive treatment for patients with AS who have a poor response to ACEI alone.