Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression.

We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30–90ml/min per 1.73m². Urine biomarkers were assayed a median of 5 months [IQR: 4–7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period.

Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression.

After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

新型尿液生物标志物可以提高对肾功能快速下降风险较高的儿童的识别，并阐明 CKD 进展的病理生理学。

我们调查了肾小管健康（EGF 和α -1 微球蛋白）、肾小管损伤（肾损伤分子-1；KIM-1）和炎症（单核细胞趋化蛋白-1 [MCP-1] 和 YKL- 40) 和 CKD 进展。前瞻性 CKD 儿童研究招募了 6 个月至 16 岁且 eGFR 为 30–90ml/min/1.73m ²的儿童。尿液生物标志物在研究入组后的中位时间为 5 个月 [IQR：4–7]。我们通过将尿液生物标志物浓度除以尿液肌酐浓度来将生物标志物索引为尿肌酐，以说明尿液的浓度。主要结果是随访期间的 CKD 进展（eGFR 下降 50% 或肾衰竭的复合结果）。

总体而言，665 名儿童中有 252 名 (38%) 在中位随访 6.5 年的时间内达到了综合结果。调整协变量后，尿液 EGF 浓度处于最低四分位数的儿童发生 CKD 进展的风险是浓度处于最高四分位数的儿童的七倍（完全调整后的风险比 [aHR]，7.1；95% 置信区间 [95 % 置信区间], 3.9 至 20.0)。与生物标志物浓度处于最低四分位数的儿童相比，尿 KIM-1、MCP-1 和α -1 微球蛋白浓度处于最高四分位数的儿童患 CKD 进展的风险也显着更高。将五种生物标志物添加到临床模型中增加了对 CKD 进展的区分和重新分类。

多变量调整后，较低的尿液 EGF 浓度和较高的尿液 KIM-1、MCP-1 和α -1 微球蛋白浓度均与儿童 CKD 进展相关。