福辛普利治疗儿童慢性肾脏病的疗效

Renoprotective Effect of Fosinopril on Pediatric Chronic Kidney Disease

目的研究血管紧张素转化酶抑制剂(ACEI)类药物福辛普利对慢性肾脏病(CKD)患儿的肾脏保护作用和疗效。方法选择2008年2月-2009年8月在本院住院确诊为激素耐药型肾病综合征(SRNS)及IgA肾病(IgAN)的患儿,随机将其分为中剂量组、低剂量组及对照组。以前瞻性研究方式记录患儿的临床资料,观察24周,定期监测其24 h尿蛋白定量(DPL)、血钾、血肌酐(SCr)、肌酐清除率(CCr)、尿β2-微球蛋白(β2-MG)、血清TGF-β1及血脂、肝功能和血常规等指标,对上述3组指标进行统计学分析。结果治疗后,2个治疗组DPL、平均动脉压、总胆固醇、三酰甘油及尿β2-MG较治疗前明显降低(Pa<0.05),中剂量组血清TGF-β1治疗后显著降低(P<0.05);治疗终点2个治疗组与对照组比较DPL、平均动脉压、尿β2-MG及血清TGF-β1均有统计学差异(Pa<0.05);但仅有中剂量组血清TGF-β1明显低于对照组。中剂量组尿蛋白第12周显著降低(P<0.05),24周转阴率78.26%;低剂量组第20周尿蛋白明显减轻(P<0.05),24周蛋白尿转阴率为42.11%,2组转阴率比较差异有统计学意义(P<0.05)。2个治疗组中高血压患儿治疗后平均动脉压[(72.40±6.10)mmHg,1 mmHg=0.133 kPa]较治疗前[(79.62±6.49)mmHg]显著下降(P<0.05),血压正常者则治疗前后无明显变化(P>0.05);但2组治疗前后尿蛋白下降显著,差异有统计学意义(Pa<0.05)。2个治疗组尿蛋白降低与血压下降无直线相关关系。结论福辛普利有独立降低尿蛋白效应,协同激素和其他免疫抑制剂能有效减轻CKD患儿尿蛋白;福辛普利能通过降低或阻断TGF-β1水平起到延缓肾脏病变进展保护肾脏的作用且有较好的耐受性。

Objective To evaluate the therapeutic effect of fosinopril on chronic kidney disease（CKD） in children,and explore the effect on renal protection. Methods From Feb.2008 to Aug.2009,CKD patients in Guangzhou Women and Children′s Medical Center were collected from the pediatric CKD diagnosed as seteroid-resistant nephrotic syndrome and IgA nephropathy,who were randomly divided into middle dose group,lower dose group,and the control group,were treated with uniform therapy plan and were prospectively measured for 24 weeks.The patients were regularly documented for their daily protein loss（DPL）,potassium,serum creatinine（SCr）,creatinine clearance rate（CCr）,β_2-microglobulin（β_2-MG）,transforming growth factor-β1（TGF-β1） and blood lipid and blood cell count at 0,2,4,8,12,16,20,24 weeks,then the data were analyzed and compared statistically. Results After treatment,the DPL,mean arterial pressure,cholesterol,triglycerides,β_2-MG in middle dose group and low dose group were decreased obviously than before treatment（P_a0.05）,but only TGF-β1 in the middle dose group decreased obviously（P0.05）.Compared with control group,the mean arterial pressure,β_2-MG and TGF-β1 in the middle dose group and the lower dose group were obviously different（P_a0.05）.In the first 12 weeks,DPL in the middle dose group significantly reduced（P0.05）,and in 24 week negative rate of proteinuria was 78.26%;DPL in 20 weeks was lihgtened obviously compared with lower dose group（P0.05）,and its proteinuria negative rate was 42.11% at the end of treatment.The difference between 2 groups was significant（P0.05）.The patients treated with fosinopril were divided into the hypertension and the normal blood presure groups at the start of the study.At finishing point,the mean arterial pressure was（72.40±6.10） mmHg（1 mmHg=0.133 kPa）,which dropped significantly in the hypertension group compared with the pretreatment[（79.62±6.49） mmHg]（P0.05）,and the normal blood pressure group did not change obviously（P0.05）.However,the decline of urinary protein in 2 groups after therapy[hypertension group（0.36±0.58） g,normal blood pressure groups（0.16±0.17） g] were also decreased compared with pre-therapy（P_a0.05）.The drop of urinary protein and blood pressure in both group was not related to each other. Conclusions It is confirmed that combining fosinopril with steroid and other immunosuppressive that can effectively relieve pediatric CKD and decreased the urinary protein,which is superior to use steroid or other immunosuppressive alone.And fosinopril′s mechanism of antiproteinurina is independently different from that of adults.Fosinopril can be reduced or blocked by TGF-β1 level to delay progression of renal advance to protect renal function.Fosinopril is safety and tolerant to peadiatrics.