Burgmaier Kathrin, Buffin-Meyer Bénédicte, Klein Julie, Becknell Brian, McLeod Daryl, Boeckhaus Jan, Gross Oliver, Dafinger Claudia, Siwy Justyna, Decramer Stéphane, Schaefer Franz, Liebau Max C, Schanstra Joost P
Department of Pediatrics, University Hospital Cologne and University of Cologne, Faculty of Medicine, Cologne, Germany.
Faculty of Applied Healthcare Science, Deggendorf Institute of Technology, Deggendorf, Germany.
Clin Kidney J. 2025 Apr 15;18(5):sfaf093. doi: 10.1093/ckj/sfaf093. eCollection 2025 May.
The diagnosis of autosomal recessive polycystic kidney disease (ARPKD) can be hampered by its pronounced phenotypic variability and ARPKD-mimicking phenocopies. Here, for the first time we specifically studied the urinary peptidome of patients with ARPKD with the aim of distinguishing ARPKD from other causes of chronic kidney disease (CKD).
Fifty-eight urine samples from patients with ARPKD, 662 urine samples from paediatric patients with CKD with various other CKD aetiologies and 45 samples from healthy children were included. The urinary peptidome was analysed by capillary electrophoresis/mass spectrometry.
A 77-peptide signature specific for ARPKD was identified. Application of this signature in a matched random validation set of 19 samples of patients with ARPKD, 23 samples from patients with other CKD and 21 samples from healthy individuals led to a sensitivity of 84.2% [95% confidence interval (CI) 60.4-96.6], a specificity of 100% (95% CI 92.0-100%) and an area under the receiver operating characteristics curve (AUC) of 0.994 (95% CI 0.93-1.00). The 77-peptide signature displayed a specificity of 76.1% (95% CI 72.4-79.5) and an AUC of 0.88 (95% CI 0.85-0.90) in 591 samples from non-matched children with various CKD aetiologies. The signature was primarily (83%) composed of collagen fragments indicating structural damage. Of the remaining peptides, five originated from proteins known to bind to calcium potentially linking the current work to defaults in calcium signalling in polycystic disease.
We determined a urinary peptide signature that identifies paediatric patients with ARPKD with high precision among a population of children with CKD. Knowledge of the identity of the underlying peptides offers a novel starting point for discussion of possible pathophysiological processes involved in ARPKD.
常染色体隐性多囊肾病（ARPKD）的诊断可能因其显著的表型变异性以及类似ARPKD的拟表型而受到阻碍。在此，我们首次专门研究了ARPKD患者的尿液肽组，目的是将ARPKD与慢性肾脏病（CKD）的其他病因区分开来。
纳入了58例ARPKD患者的尿液样本、662例患有各种其他CKD病因的儿科CKD患者的尿液样本以及45例健康儿童的样本。通过毛细管电泳/质谱法分析尿液肽组。
鉴定出了一种对ARPKD具有特异性的77肽特征图谱。将该特征图谱应用于一个匹配的随机验证集，其中包括19例ARPKD患者样本、23例其他CKD患者样本和21例健康个体样本，结果显示敏感性为84.2%[95%置信区间（CI）60.4 - 96.6]，特异性为100%（95% CI 92.0 - 100%），受试者操作特征曲线下面积（AUC）为0.994（95% CI 0.93 - 1.00）。在591例来自不同CKD病因的非匹配儿童样本中，该77肽特征图谱的特异性为76.1%（95% CI 72.4 - 79.5），AUC为0.88（95% CI 0.85 - 0.90）。该特征图谱主要（83%）由表明结构损伤的胶原片段组成。在其余的肽中，有5种来自已知与钙结合的蛋白质，这可能将当前的研究与多囊肾病中钙信号传导的缺陷联系起来。
我们确定了一种尿液肽特征图谱，可在患有CKD的儿童群体中高精度地识别患有ARPKD的儿科患者。对潜在肽的身份的了解为讨论ARPKD中可能涉及的病理生理过程提供了一个新的起点。
