儿童急性肾损伤及早期生物标记物的临床评价

儿童急性肾损伤及早期生物标记物的临床评价

目的分析兒童急性肾损伤的临床特征，探讨生物标记物对儿童AKI的诊断价值。方法选取2016年6月～2017年3月在我院儿科和中南大学湘雅二医院儿童医学中心肾内科住院的患儿60例作为研究对象，按照AKIN标准分为AKI 组（30例）和非AKI组（30例），选取同期同年龄段健康体健儿童24例作为对照组。分析AKI患儿临床特征及影响因素，观察不同组患儿尿及血清中生物标记物水平，比较不同生物标记物对AKI的诊断价值。结果引起AKI的常见疾病分别为脓毒症、药物中毒、重症过敏性紫癜和蛇咬伤。身高和体重与AKI发生有较高的相关性（P＜0.05）。入院后2 h，除SCr外，两组患儿的尿KIM-1、NGAL、L-FABPs、血清CysC及NGAL水平比较，差异均有统计学意义（P＜0.01）。入院后48 h，两组患儿的SCr水平比较，差异有统计学意义（P＜0.01）；AKI组其他各项指标水平较之前下降，但仍高于非AKI组，差异均有统计学意义（P＜0.01）。入院2 h，尿KIM-1、NGAL、L-FABP、血清CysC、NGAL及SCr诊断AKI的AUC分别为0.912、0.922、0.909、0.906、0.943和0.533。入院48 h，尿KIM-1、NGAL、L-FABP、血清CysC、NGAL及SCr诊断AKI的AUC分别为0.887、0.904、0.858、0.818、0.889和0.942。结论AKI与疾病严重程度有关。在肾脏病变的情况下，身高和体重可能是AKI发生的影响因素。血NGAL对AKI 的早期临床诊断可能具有较好的参考价值，SCr仍不失为预测AKI的一项重要指标。

[Abstract]Obiective To analyze the clinical features of pediatric acute kidney injury and to investigate the diagnostic value of biomarkers for pediatric AKI.Methods From June 2016 to March 2017，a total of 60 patients who were hospitalized in the department of pediatric in our hospital and the second xiangya hospital of central south university were selected as research objects.They were assigned to AKI group （30 cases）and non-AKI group （30 cases）according to the definition by the AKIN criteria.Also 24 healthy children of the same age were recruited as the control group.The clinical characteristics and influencing factors of AKI children were analyzed，and the biomarkers of different groups of children were observed and the diagnostic value of different biomarkers for AKI was compared.Results The common causes of AKI were sepsis，drug intoxication，severe allergic purpura and snakebite.Height and weight had a higher correlation with AKI （P＜0.05）.At 2 hours after hospitalization，except SCr，the levels of urine KIM-1，NGAL，L-FABP，serum CysC，and serum NGAL were significantly higher in AKI group than those in non-AKI group，and the differences were statistically significant （P＜0.01）.At 48 hours after hospitalization，the levels of SCr were significantly higher in AKI group than those in non-AKI group，and the differences were statistically significant（P＜0.01）.Although the levels of other biomarkers in AKI group declined，they were still significantly higher than those in non-AKI group，and the differences were statistically significant（P＜0.01）.At 2 hours after hospitalization，the value for the AUC was determined for urine KIM-1，NGAL，L-FABP，serum CysC，NGAL and SCr was 0.912，0.922，0.909，0.906，0.943 and

0.533 respectively.At 48 hours after hospitalization，the value for the AUC was determined for urine KIM-1，NGAL，L-FABP，serum CysC，NGAL and SCr was 0.887，0.904，0.858，0.818，0.889 and 0.942 respectively.Conclusions AKI is associated with the disease severity.Height and weight may be the influence factors of pediatric AKI in renal pathologic conditions.The serum level of NGAL may have good reference value for early clinical diagnosis of AKI，SCr is still an important predictor of AKI.[Key words]Acute kidney injury；Children；Blomarkers；Clinical evaluation

急性肾损伤（acute kidney injury，AKI）是指肾功能突然丧失，导致肾小球滤过率下降及水、电解质、酸碱平衡失调。AKI在儿童中并不少见[1-4]，其发生率占住院患儿的0.39%[5]，就危重症而言，甚至高达82%[4]。AKI也是危重症患儿发病率和死亡率的独立危险因素[6]。此外，约46.8%AKI患儿在后续的1～3年内存在慢性肾脏病（chronic kidney disease，CKD）风险[7]。因此，对AKI 患儿早期发现、合理干预至关重要。

AKI的诊断，传统意义上依赖于血清肌酐（serum creatinine，SCr）和尿量的检测。然而，SCr敏感度及特异度均不高[4]。尿量更是较为粗略，且易受多种因素的影响，精确度低。近年来发现了一些可能较早预测AKI发生的生物标记物，例如胱蛋白酶抑制物C（cystatin C，CysC）、肾损伤分子-1（kidney injury molecule-1，KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase associated lipocalin，NGAL）和肝型脂肪酸结合蛋白（liver-type fatty acid binding proteins，L-FABPs）等[8-11]。但其临床应用尚存有争议，尤其对儿童AKI早期评估的价值鲜有报道。本研究以60例患儿作为研究对象，分析AKI患儿的临床特点及可能发生的危险因素，评估生物标记物对AKI的诊断价值，以期为儿童AKI的早期防治提供帮助，现报道如下。

1资料与方法

1.1一般资料

收集2016年6月～2017年3月我院儿科及中南大学湘雅二医院儿童医学中心肾内科的住院患儿60例，患儿因血、尿、组织学及影像学检查发现异常且病程在3个月内。排除标准：病程≥3个月CKD患儿或有遗传性疾病及家族史的患儿。按照2005年AKIN标准[12]，48 h内SCr升高≥26.4 mol/L或较原SCr升高≥50%。将60例患儿分为AKI组（30例）和非AKI组（30例）。选取同期同年龄正常健康体查儿童24例作为对照组。本研究经医院医学伦理委员会批准和同意，所有入选患儿的家长均签署知情同意书。

1.2方法

分别留取60例患儿入院即刻、2 h和48 h的空腹静脉血各4 ml，并留取入院2 h、48 h的尿液各10 ml，离心后取上清液置于-80℃冰箱保存待检。对照组标本为体检后剩余尿液及血清，保存待检，与入选患儿进行基线水平（AKI组与