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首页> 外国专利> USE OF AMNIOTIC FLUID PEPTIDES FOR PREDICTING POSTNATAL RENAL FUNCTION IN CONGENITAL ANOMALIES OF THE KIDNEY AND THE URINARY TRACT

USE OF AMNIOTIC FLUID PEPTIDES FOR PREDICTING POSTNATAL RENAL FUNCTION IN CONGENITAL ANOMALIES OF THE KIDNEY AND THE URINARY TRACT

机译：使用羊水肽预测肾脏和泌尿道先天性异常中的产后肾功能

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Bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the main cause of childhood chronic kidney disease (CKD). Accurate and non-biased prenatal prediction of postnatal disease evolution is currently lacking, but is essential for prenatal counseling and disease management. Here the inventors aimed to develop an objective and quantifiable risk prediction method based on amniotic fluid (AF) peptides. 178 fetuses with bilateral CAKUT were included in a prospective multicenter study. The AF peptide content was studied using capillary electrophoresis coupled to mass spectrometry. The endpoint was early-onset renal failure (CKD stage 3-5) or death due to end-stage renal disease at two years of age. Among the ~7000 peptide candidates, 98 were associated with early severe renal failure. The most frequently found peptides associated with severe disease were fragments from extracellular matrix proteins and thymosin-P4. Combination of those 98 peptides in a classifier lead to the prediction of postnatal renal outcome in a blinded validation set of 51 patients with a 88% (95%CI: 64-98) sensitivity, 97% (95%CI: 85-100) specificity and an AUC of 0.96 (95%CI: 0.87-1.00), outperforming predictions based on currently used clinical methods. The classifier also predicted normal postnatal renal function in 75% of terminated pregnancies where fetopathology showed kidneys compatible with normal life. Analysis of AF peptides thus allows a precise and quantifiable prediction of postnatal renal function in bilateral CAKUT with potential major impact on pre- and postnatal disease management.
机译：肾脏和泌尿道（Cakut）的双侧先天性异常是儿童慢性肾病（CKD）的主要原因。目前缺乏治疗后期疾病演化的准确性和非偏见产前预测，但对于产前咨询和疾病管理是必不可少的。这里的发明人旨在基于羊水（AF）肽的目标和可量化的风险预测方法。 178个具有双侧Cakut的胎儿包含在预期的多中心研究中。使用毛细管电泳与质谱法一起研究AF肽含量。终点是早发肾功能衰竭（CKD阶段3-5）或由于终末期肾病而死亡两年龄段。在〜7000名肽候选者中，98例与早期严重的肾功能衰竭有关。与严重疾病相关的最常见的肽是细胞外基质蛋白和胸腺素-P4的片段。分类器中的那些98肽的组合导致盲验验证套装的预测到88％（95％CI：64-98）敏感性，97％（95％CI：85-100）特异性和0.96的AUC（95％CI：0.87-1.00），基于目前使用的临床方法表现优于预测。分类器还预测了75％终止妊娠的正常产后肾功能，胎病理学显示肾脏与正常生活相容。因此，AF肽的分析允许对双侧CAKUT的后期肾功能进行精确和可量化的预测，其对出生前疾病管理有潜在的重大影响。

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