Boeckhaus Jan, Tönshoff Burkhard, Weber Lutz T, Pape Lars, Latta Kay, Fehrenbach Henry, Lange-Sperandio Baerbel, Kettwig Matthias, König Sabine, John-Kroegel Ulrike, Gellermann Jutta, Galiano Matthias, Jami Sima, Pieper Dennis, Dihazi Gry Helene, Hafke Angelika, Kohl Stefan, Liebau Max C, König Jens, Haffner Dieter, Gross Oliver, Wallbach Manuel
Clinic for Nephrology and Rheumatology, University Medical Center Göttingen, Goettingen, Germany.
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.
Pediatr Nephrol. 2025 Jul;40(7):2205-2213. doi: 10.1007/s00467-025-06696-3. Epub 2025 Feb 4.
Chronic kidney disease (CKD) seriously affects the well-being and shortens the life expectancy of children and adolescents, but its progression is challenging to predict. Therefore, there is an urgent need for biomarkers that can identify children at risk of faster CKD progression. Alport syndrome (AS) is the most common monogenetic glomerular kidney disease. Urinary Dickkopf-related protein 3 (DKK3) is associated with a decline in estimated glomerular filtration rate (eGFR) in adults and children with advanced CKD. However, its potential for early detection of CKD and its prognostic value in children with AS remain unknown.
Urine samples from 49 children enrolled in the EARLY PRO-TECT Alport trial were analyzed to evaluate whether DKK3 could identify children with AS to be at risk for faster CKD progression.
DKK3 levels in patients with AS were higher than those of healthy individuals reported in the literature. DKK3 levels were more elevated in patients with later stages of AS. Furthermore, children who were not treated with renin angiotensin system inhibitors (RASi) had higher DKK3 levels than treated children. Children with above-average DKK3 levels were more likely to have increased albuminuria after 2 years of follow-up than children with below-average DKK3 levels.
Urinary DKK3 is significantly elevated in children at early stages of AS. There was a potential association between higher DKK3 levels, worsening albuminuria, and a decline in kidney function. These findings suggest that DKK3 may be a prognostic marker for predicting the risk of kidney damage in children with AS.
慢性肾脏病（CKD）严重影响儿童和青少年的健康并缩短其预期寿命，但其进展难以预测。因此，迫切需要能够识别有CKD快速进展风险儿童的生物标志物。Alport综合征（AS）是最常见的单基因肾小球肾病。尿Dickkopf相关蛋白3（DKK3）与晚期CKD成人和儿童的估计肾小球滤过率（eGFR）下降有关。然而，其在CKD早期检测中的潜力及其在AS儿童中的预后价值仍不清楚。
对参加EARLY PRO-TECT Alport试验的49名儿童的尿液样本进行分析，以评估DKK3是否能识别有AS且有CKD快速进展风险的儿童。
AS患者的DKK3水平高于文献报道的健康个体。AS晚期患者的DKK3水平升高更明显。此外，未接受肾素血管紧张素系统抑制剂（RASi）治疗的儿童的DKK3水平高于接受治疗的儿童。随访2年后，DKK3水平高于平均水平的儿童比DKK3水平低于平均水平的儿童更有可能出现蛋白尿增加。
AS早期儿童的尿DKK3显著升高。DKK3水平升高、蛋白尿恶化和肾功能下降之间可能存在关联。这些发现表明，DKK3可能是预测AS儿童肾损伤风险的预后标志物。
