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小儿常染色体显性多囊肾病(ADPKD)的早期尿液生物标志物:未发现支持尿液中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)的证据。

Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL).

作者信息

Tsingos Marianthi, Merlini Laura, Solcà Marco, Goischke Alexandra, Wilhelm-Bals Alexandra, Parvex Paloma

机构信息

Pediatric Nephrology Unit, Department of Pediatrics, Children's Hospital, Geneva University Hospital, Geneva, Switzerland.

Pediatric Radiology Unit, Department of Radiology, Children's Hospital, Geneva University Hospital, Geneva, Switzerland.

出版信息

Front Pediatr. 2019 Mar 22;7:88. doi: 10.3389/fped.2019.00088. eCollection 2019.

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. No curative treatment is available and early detection and diagnosis confronts pediatricians with the lack of early markers to decide whether to introduce renal-protective agents and prevent the progression of renal failure. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population. Urinary NGAL (uNGAL) levels were measured in 15 ADPKD children and compared with 15 age and gender matched controls using parametric, non-parametric, and Bayesian statistics. We also tested the association of uNGAL levels with markers of disease progression, such as proteinuria, albuminuria, blood pressure, and Total Kidney Volume (TKV) using correlation analysis. TKV was calculated by ultrasound, using the ellipsoid method. No difference in mean uNGAL levels was observed between groups (ADPKD: 26.36 ng/ml; Controls: 27.24 ng/ml; = 0.96). Moreover, no correlation was found between uNGAL and proteinuria ( = 0.51), albuminuria ( = 0.69), TKV ( = 0.68), or mean arterial pressure ( = 0.90). By contrast, TKV was positively correlated with proteinuria ( = 0.04), albuminuria ( = 0.001), and mean arterial pressure ( = 0.03). uNGAL did not confirm its superiority as a marker of disease progression in a pediatric ADPKD population. In the contrary, TKV appears to be an easy measurable variable and may be promising as a surrogate marker to follow ADPKD progression in children.

摘要

常染色体显性遗传性多囊肾病(ADPKD)在儿童期因家族史阳性患者出现肾囊肿而被越来越多地诊断出来。目前尚无治愈性治疗方法,早期检测和诊断使儿科医生面临缺乏早期标志物的问题,难以决定是否引入肾脏保护剂并预防肾衰竭的进展。中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是一种肾小管蛋白,最近被提议作为ADPKD成年人群肾损伤的早期生物标志物。对15名ADPKD儿童的尿NGAL(uNGAL)水平进行了测量,并使用参数统计、非参数统计和贝叶斯统计方法与15名年龄和性别匹配的对照进行了比较。我们还使用相关分析测试了uNGAL水平与疾病进展标志物(如蛋白尿、白蛋白尿、血压和总肾体积(TKV))之间的关联。TKV通过超声使用椭球体法计算。两组之间未观察到平均uNGAL水平的差异(ADPKD组:26.36 ng/ml;对照组:27.24 ng/ml;P = 0.96)。此外,未发现uNGAL与蛋白尿(P = 0.51)、白蛋白尿(P = 0.69)、TKV(P = 0.68)或平均动脉压(P = 0.90)之间存在相关性。相比之下,TKV与蛋白尿(P = 0.04)、白蛋白尿(P = 0.001)和平均动脉压(P = 0.03)呈正相关。在儿科ADPKD人群中,uNGAL并未证实其作为疾病进展标志物的优越性。相反,TKV似乎是一个易于测量的变量,有望作为监测儿童ADPKD进展的替代标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dd4/6439434/9838013c910a/fped-07-00088-g0001.jpg

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