原发性肾病综合征患儿尿MCP-1、IL-18的检测及临床意义
원발성신병종합정환인뇨MCP-1、IL-18적검측급림상의의
Detection and clinical significance of urinary monocyte chemoattractant protein-1 and interleukin-18 in children with primary nephrotic syndrome
  • 万方数据
    中国医师杂志 중국의사잡지
    JOURNAL OF CHINESE PHYSICIAN
    2013年 5期 621-625 ,共5页

    吴芳%方琪玮%崔建军

    오방%방기위%최건군

    肾病综合征/尿%儿童%趋化因子CCL2/尿%白细胞介素18/尿 腎病綜閤徵/尿%兒童%趨化因子CCL2/尿%白細胞介素18/尿
    신병종합정/뇨%인동%추화인자CCL2/뇨%백세포개소18/뇨
    Nephrotic syndrome/urine%Child%Chemokine CCL2/urine%Interleukin-18/urine
    目的 检测原发性肾病综合征(primary nephrotic syndrome,PNS)患儿不同时间点尿液中单核细胞趋化蛋白-1(MCP-1)及IL-18的含量,探讨其与PNS的发生、发展、反复及预后有无相关性.方法 选取65例初发PNS患儿为研究对象,根据对激素效应及随访结果分为三组:激素敏感型肾病综合征(steroid-sensitive NS,SSNS) 35例,激素耐药型肾病综合征(steroid-resistant NS,SRNS)15例,频反复肾病综合征(frequent-relapse NS,FRNS) 15例.另取20例健康体检儿童作为正常对照组.分别在发病初期未用糖皮质激素时、足量激素治疗8周时、足量激素治疗16周或病情反复时采集外周血标本及尿标本.采用ELISA法检测患儿不同时间点尿液中单核细胞趋化蛋白-1(MCP-1)及IL-18的水平,并采用全自动生化分析仪测定PNS患儿不同时间点血尿素氮、肌酐及24h尿蛋白定量.结果 (1)SSNS组治疗前、治疗后8周尿IL-18水平均高于对照组[治疗前(160.30±27.29) pg/ml,治疗后(157.62±26.85) pg/ml,对照组(70.88±14.43) pg/ml]；治疗16周后MCP-1、IL-18水平显著低于治疗前、治疗后8周[治疗16周(20.98±4.53)pg/ml,(79.09±7.23)pg/ml,P＜0.05].(2)SRNS组治疗前尿MCP-1及IL-18水平显著高于SSNS组治疗前与对照组[SRNS组治疗前(76.84±5.58)pg/ml,(252.37±25.34) pg/ml,P＜0.05],但与治疗后8周比较差异无统计学意义[治疗8周(72.32±4.30) pg/ml,(243.70±35.43) pg/ml,P＞0.05],当联合免疫抑制剂环磷酰胺治疗16周后则显著低于治疗前、治疗后8周[治疗16周(34.03±2.56) pg/ml,(114.42±21.33) pg/ml,P均＜0.05].(3)FRNS组治疗前、治疗后8周尿MCP-1及IL-18水平与SSNS组比较差异无统计学意义[FRNS组治疗前(30.43±4.61) pg,/ml,(156.65±34.39) pg/ml,治疗8周(29.41±4.76)pg/ml,(152.21±34.73)pg/ml,P＞0.05]；但显著低于SRNS组(P＜0.05),当病情反复时,与治疗前、治疗后8周及对照组比较尿MCP-1及IL-18水平显著增高,差异有统计学意义(P＜0.05)[病情反复时(72.92±3.01)pg/ml,(224.33±26.07) pg/ml].(4)尿MCP-1及IL-18水平与血尿素氮、肌酐之间无相关(P＞0.05),与24 h尿蛋白定量呈正相关(r=0.706,0.556,P＜0.01).尿MCP-1水平与尿IL-18水平呈正相关(r=0.811,P＜0.01).结论 PNS患儿尿MCP-1及IL-18水平的检测有助于早期预测患儿对糖皮质激素的敏感性,二者水平升高结合PNS患儿的临床症状及蛋白尿等指标可作为监测肾病反复的无创的重要指标.
    목적 검측원발성신병종합정(primary nephrotic syndrome,PNS)환인불동시간점뇨액중단핵세포추화단백-1(MCP-1)급IL-18적함량,탐토기여PNS적발생、발전、반복급예후유무상관성.방법 선취65례초발PNS환인위연구대상,근거대격소효응급수방결과분위삼조:격소민감형신병종합정(steroid-sensitive NS,SSNS) 35례,격소내약형신병종합정(steroid-resistant NS,SRNS)15례,빈반복신병종합정(frequent-relapse NS,FRNS) 15례.령취20례건강체검인동작위정상대조조.분별재발병초기미용당피질격소시、족량격소치료8주시、족량격소치료16주혹병정반복시채집외주혈표본급뇨표본.채용ELISA법검측환인불동시간점뇨액중단핵세포추화단백-1(MCP-1)급IL-18적수평,병채용전자동생화분석의측정PNS환인불동시간점혈뇨소담、기항급24h뇨단백정량.결과 (1)SSNS조치료전、치료후8주뇨IL-18수평균고우대조조[치료전(160.30±27.29) pg/ml,치료후(157.62±26.85) pg/ml,대조조(70.88±14.43) pg/ml]；치료16주후MCP-1、IL-18수평현저저우치료전、치료후8주[치료16주(20.98±4.53)pg/ml,(79.09±7.23)pg/ml,P＜0.05].(2)SRNS조치료전뇨MCP-1급IL-18수평현저고우SSNS조치료전여대조조[SRNS조치료전(76.84±5.58)pg/ml,(252.37±25.34) pg/ml,P＜0.05],단여치료후8주비교차이무통계학의의[치료8주(72.32±4.30) pg/ml,(243.70±35.43) pg/ml,P＞0.05],당연합면역억제제배린선알치료16주후칙현저저우치료전、치료후8주[치료16주(34.03±2.56) pg/ml,(114.42±21.33) pg/ml,P균＜0.05].(3)FRNS조치료전、치료후8주뇨MCP-1급IL-18수평여SSNS조비교차이무통계학의의[FRNS조치료전(30.43±4.61) pg,/ml,(156.65±34.39) pg/ml,치료8주(29.41±4.76)pg/ml,(152.21±34.73)pg/ml,P＞0.05]；단현저저우SRNS조(P＜0.05),당병정반복시,여치료전、치료후8주급대조조비교뇨MCP-1급IL-18수평현저증고,차이유통계학의의(P＜0.05)[병정반복시(72.92±3.01)pg/ml,(224.33±26.07) pg/ml].(4)뇨MCP-1급IL-18수평여혈뇨소담、기항지간무상관(P＞0.05),여24 h뇨단백정량정정상관(r=0.706,0.556,P＜0.01).뇨MCP-1수평여뇨IL-18수평정정상관(r=0.811,P＜0.01).결론 PNS환인뇨MCP-1급IL-18수평적검측유조우조기예측환인대당피질격소적민감성,이자수평승고결합PNS환인적림상증상급단백뇨등지표가작위감측신병반복적무창적중요지표.
    Objective To investigate the concentration of monocyte chemoattractant protein-1 (MCP-1) and interleukin-18 (IL-18) in the urinary of children with primary nephrotic syndrome(PNS) at different time points,and to explore their correlation with occurrence,development,progression,and prognosis of PNS.Methods A total of 65 pediatric cases from our hospital was enrolled in this study,and was divided into three groups based on the retrospective the follow-up results including steroid-sensitive NS (SSNS) (n =35),steroid-resistant NS (SRNS) (n =15),and frequent-relapse NS (FRNS) (n =15) groups.Another 20 healthy children served as normal controls.Peripheral blood samples and urine specimen were collected at three time points (without glucocorticoids,treatment after 8 weeks,and treatment after 16 weeks or recurrence).The levels of MCP-1 and IL-18 in the urine were assayed by enzyme-linked immunosorbent assay (ELISA).The levels of blood urea nitrogen,creatinine,and 24-hour urinary protein excretion were assayed by full-automatic biochemical study appliance.Results (1)In SSNS group,the levels of urinary IL-18 before treatment and treated for 8 weeks were higher than the normal control group [before treatment:(160.30 ±27.29) pg/ml; treated for 8 weeks:(157.62 ±26.85) pg/ml; normal control group:(70.88 ± 14.43) pg/ul].However,after treated for 16 weeks,the levels of urinary MCP-1 and IL-18 were markedly decreased compared with that of control group and those before treatment and treated for 8 weeks [treated for 16 weeks:(20.98 ±4.53) pg/ml,and (79.09 ±7.23) pg/ml,P ＜0.05].(2)In SRNS group,the levels of urinary MCP-1 and IL-18 before treatment were remarkably higher than that of control group and that of SSNS group before treatment[SSNS group before treatment:(76.84 ± 5.58) pg/ml,and (252.37 ± 25.34)pg/ml,P ＜0.05],but no significant difference was found when it was compared with that treated for 8 weeks [treated for 8 weeks:(72.32 ±4.30) pg/ml,and (243.70 ±35.43) pg/ml,P ＞0.05] ; However,its level was markedly decreased after treated with immunosuppressants of CTX for 16 weeks when it was compared with those before treatment and treated for 8 weeks[treated for 16 weeks:(34.03 ± 2.56) pg/ ml,and (114.42 ± 21.33)pg/ml,P ＜ 0.05].(3)In FRNS group,the levels of urinary MCP-1 and IL-18 were no remarkable difference between control and SSNS groups [before treatment:(30.43 ± 4.61) pg/ml,and (156.65 ± 34.39)pg/ml; treated for 8 weeks:(29.41 ± 4.76) pg/ml,and (152.21 ± 34.73) pg/ml,P ＞ 0.05],but its level was markedly lower than SRNS group (P ＜ 0.05).When it was recurred,the levels of urinary MCP-1 and IL-18 were significantly increased compared with before treatment and treated for 8 weeks[recurred:(72.92 ±3.01)pg/ml,and (224.33 ±26.07)pg/ml,P ＜0.05].(4)No correlation was found between the levels of MCP-1 and IL-18 and the levels of blood urea nitrogen and creatinine (P ＞0.05).Positive correlation was found between the levels of MCP-1 and IL-18 and the 24-hour urinary protein excretion (r =0.706,0.556,P ＜0.01).There's a correlation between urinary MCP-1 and IL-18 (r =0.811,P ＜ 0.01).Conclusions For children with PNS,the detection of urinary MCP-1 and IL-1 8 contributed to the early prediction of children'sensitivity on glucocorticoid.The elevated levels of urinary MCP-1 and IL-18 in combination with clinical symptoms and proteinuria can be used as an important noninvasive marker to monitor PNS recurrence.
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