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.

Study Design

Prospective longitudinal cohort study.

Setting & Participants

565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study.

Exposure

Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval.

Outcome

CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR).

Analytic Approach

Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders.

Results

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.

Limitations

Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis.

Conclusions

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.

中文翻译：

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血浆可溶性尿激酶纤溶酶原激活剂受体 (suPAR) 和儿童 CKD 进展。

基本原理和目标

可溶性尿激酶纤溶酶原激活物受体 (suPAR) 是一种与慢性肾脏病 (CKD) 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，尽管这些发现仍然是初步的，仅限于单个时间点，并且在儿科队列中未复制。

学习规划

前瞻性纵向队列研究。

设置与参与者

565 名 1 至 16 岁的参与者参加了儿童慢性肾脏病 (CKiD) 研究。

接触

血浆 suPAR 水平，按四分位数分类，在研究开始和 6 个月的随访间隔时测量。

结果

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 50% 以上。

分析方法

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。

结果

在调整人口统计学和传统 CKD 风险因素后，与最低四分位数相比，最高 suPAR 四分位数的参与者进展速度快 54% ( P  < 0.001)。将 eGFR 添加到模型中会降低风险，尽管与最低四分位数相比，最高四分位数的进展速度快 33% ( P  = 0.008)。血浆 suPAR 水平在 6 个月内几乎没有变化。

限制

残留混杂的可能性，依赖观察数据，用于亚组分析的 eGFR 较高的患者相对较少。

结论

较高的 suPAR 水平与肾脏替代治疗的时间较短或 CKD 儿童的 eGFR 减半有关。这种关联在回归建模中包含 eGFR 后略有减弱，但对于具有最高 suPAR 水平的参与者来说仍然是一个重要的关联。