Division of Pediatric Nephrology, Children's Mercy Kansas City, University of Missouri-Kansas City School of Medicine, Kansas City, MO.
Johns Hopkins School of Medicine, Baltimore, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Am J Kidney Dis. 2020 Aug;76(2):194-202. doi: 10.1053/j.ajkd.2019.11.004. Epub 2020 Jan 24.
RATIONALE & OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts.
Prospective longitudinal cohort study.
SETTING & PARTICIPANTS: 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study.
Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval.
CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR).
Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders.
Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P < 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P = 0.008). Plasma suPAR levels showed little change over 6 months.
Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis.
Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.
可溶性尿激酶型纤溶酶原激活物受体（suPAR）是一种与慢性肾脏病（CKD）事件相关的新型生物标志物，已被确定为儿童 CKD 进展的独立危险因素，尽管这些发现仍是初步的，仅局限于一个时间点，并且在儿科队列中尚未得到复制。
前瞻性纵向队列研究。
565 名年龄在 1 至 16 岁的参与者参加了儿童慢性肾脏病（CKiD）研究。
在研究开始时和 6 个月的随访间隔测量血浆 suPAR 水平，分为四分位数。
CKD 进展，定义为开始肾脏替代治疗（透析或移植）或估计肾小球滤过率（eGFR）下降超过 50%。
使用对数正态生存模型估计血浆 suPAR 四分位数与 CKD 进展风险之间的关联，调整潜在的混杂因素。
在调整人口统计学和传统 CKD 危险因素后，suPAR 四分位数最高的参与者与四分位数最低的参与者相比，进展速度快 54%（P<0.001）。在模型中加入 eGFR 后，风险有所减弱，尽管四分位数最高的参与者与四分位数最低的参与者相比，进展速度仍快 33%（P=0.008）。suPAR 水平在 6 个月内变化不大。
存在残余混杂因素的可能性，依赖观察性数据，亚组分析中 eGFR 较高的患者相对较少。
较高的 suPAR 水平与 CKD 儿童接受肾脏替代治疗或 eGFR 减半的时间更短相关。在回归模型中纳入 eGFR 后，这种关联略有减弱，但对于 suPAR 水平最高的参与者，这种关联仍然显著。
