早产儿高胆红素血症与肾损伤的关系研究

Research on the relationship between hyperbilirubinemia and kidney injury in prematures

目的探讨早产儿高胆红素血症与肾损伤的关系。方法选择2015年3~9月,在宜宾市第一人民医院新生儿科住院治疗的20例早产儿高胆红素血症患儿（黄疸组）及15例无高胆红素血症早产儿（对照组）为研究对象,并根据早产儿入院时血清总胆红素（TSB）浓度,将黄疸组进一步分为轻度黄疸亚组（n=9）和重度黄疸亚组（n=11）。采集受试者静脉血及尿液检测TSB浓度、血清胱抑素C、尿微量白蛋白（mAlb）、尿α1-微球蛋白（MG）及尿β2-MG含量。统计学比较黄疸组与对照组间TSB浓度、血清胱抑素C及上述3项尿微量蛋白含量差异,黄疸组不同类型肾损伤早产儿胎龄、出生体重、TSB浓度、日龄、病程及生后首次出现黄疸时间差异,以及黄疸组患儿各临床观察指标间相关性。本研究遵循的程序符合宜宾市第一人民医院人体试验委员会制定的伦理学标准,得到该委员会批准,征得受试对象监护人知情同意,并与监护人签署临床研究知情同意书。黄疸组与对照组患儿性别构成比、胎龄、出生体重及日龄比较,差异均无统计学意义（P〉0.05）。结果 1轻度和重度黄疸亚组的尿mAlb[（13.3±7.8）mg/L、（15.1±11.9）mg/L],尿α1-MG[（21.2±12.9）mg/L、（15.6±11.5）mg/L]及尿β2-MG[（5.6±3.7）mg/L、（5.3±3.8）mg/L]含量均分别较对照组高[（6.8±2.3）mg/L、（8.0±2.5）mg/L、（1.3±1.0）mg/L],且差异有统计学意义（P〈0.05）;但轻度与重度黄疸亚组的上述3项尿微量蛋白指标比较,差异则无统计学意义（P〉0.05）。轻度、重度黄疸亚组及对照组之间血清胱抑素C含量比较,差异均无统计学意义（P〉0.05）。2单纯肾小管损伤、混合型肾损伤及无肾损伤患儿的胎龄、出生体重和TSB浓度比较,差异均无统计学意义（P〉0.05）。单纯肾小管损伤患儿的日龄、病程和生后首次出现黄疸时间[（4.1±3.1）d、（1.3±0.8）d、（2.9±2.3）d]均分别较无肾损伤患儿[（14.6±8.2）d、（6.2±3.8）d、（8.4±4.9）d]小、短和早,混合型肾损伤患儿的生后首次出现黄疸时间[（3.8±2.2）d]较无肾损伤患儿早,单纯肾小管损伤患儿的日龄和病程较混合型肾损伤患儿[（9.8±6.6）d、（6.0±5.5）d]小和短,上述差异均有统计学意义（P〈0.05）。3黄疸组患儿尿mAlb和尿α1-MG之间（r=0.822）,尿mAlb和尿β2-MG之间（r=0.769）,以及尿α1-MG和尿β2-MG之间（r=0.660）均呈直线正相关关系（P〈0.001）。尿α1-MG及尿β2-MG与生后首次出现黄疸时间均呈直线负相关关系（r=-0.534、-0.508,P〈0.05）。结论早产儿高胆红素血症可导致肾损伤,日龄、病程和生后首次出现黄疸时间可能与肾损伤类型相关。3项尿微量蛋白联合检测,可作为早产儿高胆红素血症性肾损伤的早期诊断指标。

Objective To investigate the relationship between hyperbilirubinemia and kidney injury in prematures.Methods A total of 20 prematures with hyperbilirubinemia（as jaundice group）and 15 prematures without jaundice（as control group）,who were hospitalized in First People′s Hospital of Yibin from March to September 2015,were chosen as study objects.Prematures in jaundice group were further divided into two subgroups：mild jaundice subgroup（n=9）and severe jaundice subgroup（n=11）according to the concentration of total serum bilirubin（TSB）on admission.Peripheral vein blood and urine of all subjects were collected to detect the concentration of TSB,the contents of serum cystatin C,urine microalbumin（mAlb）,α1-microglobulin（α1-MG） andβ2-microglobulin（β2-MG）.Statistically compared the differences of contents of serum cystatin C and three above-mentioned urinary microprotein between jaundice group and control group,as well as compared the differences of gestational age,birth weight,TSB concentration,day-age of admission,course of disease and the first appearance time of jaundice among prematures with different types of kidney injury.Besides,correlation analysis among various clinical observational indicators were also done.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of First People′s Hospital of Yibin.Informed consent was obtained from the parents of each participant.There were no significant differences between jaundice group and control group in gender constituent ratio, gestational age, birth weight and day-age of admission（P〈0.05）.Results 1Content levels of mild and severe jaundice subgroup in urinary mAlb[（13.3±7.8）mg/L,（15.1±11.9）mg/L],urinaryα1-MG[（21.2±12.9）mg/L,（15.6±11.5）mg/L]and urinaryβ2-MG[（5.6±3.7）mg/L,（5.3±3.8）mg/L]were higher than those in control group[（6.8±2.3）mg/L,（8.0±2.5）mg/L,（1.3±1.0）mg/L],respectively,and the differences were statistically significant（P〈0.05）.But,there were no significant differences between mild and severe jaundice subgroups in three above-mentioned urinary microproteins（P〈0.05）.There were no significant differences among mild jaundice subgroup,severe jaundice subgroup and control group in serum cystatin C（P〈0.05）.2There were no significant differences among prematures with simple renal tubule injury,mixed kidney injury and no kidney injury in gestational age,birth weight and TSB concentration（P〈0.05）.The day-age of admission,course of disease and the first appearance time of jaundice of prematures with simple renal tubule injury[（4.1±3.1）d,（1.3±0.8）d,（2.9±2.3）d]were smaller,shorter and earlier than those of prematures with no kidney injury[（14.6±8.2）d,（6.2±3.8）d,（8.4±4.9）d],respectively.The first appearance time of jaundice of prematures with mixed kidney injury [（3.8±2.2）d]was earlier than that of prematures with no kidney injury.Furthermore,both the day-age of admission and course of disease of prematures with simple renal tubule injury were smaller and shorter than those of prematures with mixed kidney injury[（9.8±6.6）d,（6.0±5.5）d].And all above-mentioned differences were statistically significant（P〈0.05）.3There were positive correlation between urinary mAlb and urinaryα1-MG（r=0.822）,between urinary mAlb and urinaryβ2-MG（r=0.769）,between urinaryα1-MG and urinaryβ2-MG（r=0.660）in jaundice group（P〈0.001）.There were negative correlation between urinaryα1-MG or urinaryβ2-MG with the first appearance time of jaundice in jaundice group（r=-0.534,-0.508;P〈0.05）.Conclusions Hyperbilirubinemia could induce kidney injury in prematures.The types of kidney injury maybe related to day-age of admission,course of disease and the first appearance time of jaundice.Joint detection of three above-mentioned urinary microproteins could be served as early diagnosis indicators for kidney injury associated with hyperbilirubinemia in prematures.