Importance  Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C–derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults.

Objective  To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD.

Design, Setting, and Participants  Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016.

Exposures  Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m², or initiation of renal replacement therapy.

Main Outcomes and Measures  The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m².

Results  Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m². The 5-year end point–free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m², higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007).

Conclusions and Relevance  Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.

重要性  诊断和监测儿童慢性肾脏病（CKD）的常规方法，例如肌酐水平和半胱氨酸蛋白酶抑制剂C推导的估计肾小球滤过率（eGFR）以及评估尿液中现货或定时尿液中蛋白尿的价值，在识别患者方面价值有限有进行性肾功能丧失的风险。血清可溶性尿激酶受体（suPAR）水平强烈预测成人的CKD 3期事件。

目的  确定suPAR水平升高是否与CKD患儿的肾脏疾病进展有关。

设计，背景和参与者  对2个预期随访的小儿CKD队列进行事后分析，即ESCAPE试验（1999-2007年）和4C研究（2010-2016年），入组时测量血清suPAR水平，前瞻性测量纵向eGFR 。在这2项试验中，在13个欧洲国家的30所（ESCAPE试验； n = 256）和55处（4C研究； n = 642）三级医院中，共观察到898名儿童。肾脏诊断包括先天性肾脏和尿路异常（n = 637 [70.9％]），肾小管间质性肾病（n = 92 [10.2％]），肾小球肾病（n = 69 [7.7％]），缺血后CKD（n = 42） [4.7％]）和其他CKD（n = 58 [6.5％]）。总随访时间长达7.9年，中位随访时间为3.1年。分析时间为2016年10月至2016年12月。

  入组时测量暴露水平的血清suPAR水平，在ESCAPE试验中每2个月测量一次eGFR，在4C研究中每6个月测量一次eGFR。CKD进展的主要终点是eGFR降低50％，eGFR低于10 mL / min / 1.73 m ²或开始肾脏替代治疗的复合物。

主要结果和措施  这项研究的主要终点是肾脏存活，定义为50％的GFR消失持续至少1个月，开始肾脏替代治疗或eGFR低于10 mL / min / 1.73 m ²。

结果  包括898名儿童中，有560名（62.4％）为男性，入组时的平均（SD）患者年龄为11.9（3.5）岁。平均（SD）eGFR为34（16）mL / min / 1.73 m ²。suPAR水平最低的四分之一儿童的5年无终点肾存活率为64.5％（95％CI，57.4-71.7），而最高四分位数的儿童为35.9％（95％CI，28.7-43.0） （P  <.001）。通过多变量分析，肾小球病患儿达到终点的风险较高，并且随着年龄，血压，蛋白尿和基线eGFR降低而增加。基线eGFR大于40 mL / min / 1.73 m ^2的患者，对传统危险因素进行调整后，较高的对数转化suPAR水平与CKD进展的较高风险相关（危险比，5.12； 95％CI，1.56-16.7；P  = .007）。

结论和相关性  suPAR水平高的患者更容易发生肾脏疾病。进一步的研究应确定suPAR水平是否可以确定有患未来CKD危险的儿童。