How Guo Yuan, Chang Kenneth Tou En, Jacobsen Anette Sundfor, Yap Te-Lu, Ong Caroline Choo Phaik, Low Yee, Allen John Carson, Kuick Chik Hong, Lim Malcolm Zhun Leong, Laksmi Narasimhan Kannan
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
J Pediatr Urol. 2018 Feb;14(1):51.e1-51.e7. doi: 10.1016/j.jpurol.2017.07.014. Epub 2017 Sep 1.
Congenital pelviureteric junction obstruction (PUJO) is one of the most frequent causes of neonatal hydronephrosis. Obstruction at the PUJ has potential severe adverse outcomes, such as renal damage. While pyeloplasty has been established as the definitive treatment, the exact pathophysiology of congenital PUJO remains unknown. Recent research has proposed neuronal innervation defects as an etiological factor in congenital PUJO. We aim to study the expression of various neuronal markers in PUJO specimens compared with controls, and evaluate whether severity of renal disease or dysfunction pre-operatively is related to expression of neuronal markers in resected PUJO specimens.
All consecutive patients who underwent dismembered pyeloplasty at KK Women's and Children's Hospital, Singapore, for intrinsic PUJO from 2008 to 2012 were included. Patients with other co-occurring renal pathologies were excluded. Controls were obtained from nephrectomy patients with Wilm's tumor or other benign renal conditions during the same period. Specimens were stained immunohistochemically with neuronal markers protein gene product 9.5 (PGP9.5), synaptophysin, and S-100, and with CD-117, a marker for interstitial cells of Cajal (Table). Levels of expression of the markers were assessed semiquantitatively (decreased, increased or no change) in comparison with controls by two independent observers. Pre-operative data of patients' renal anatomical (ultrasonography measurements of renal pelvis size) and functional parameters (differential renal function measured using MAG-3 renal scans) were obtained.
Thirty-eight PUJO specimens (38 renal units) and 20 controls were studied. Mean patient age at pyeloplasty was 25.3 months (2.9-167.6 months). Median pre-operative pelvic size was 25.0 mm (17.0-50.0 mm). Both PUJO specimens and controls showed great heterogeneity in distribution of innervation. All four immunohistochemical markers were not predictive of significant pre-operative renal pelvis dilation or pre-operative diminished renal function of the operated kidney.
There exists marked variability in expression of neuronal markers synaptophysin, PGP9.5, and S-100, and CD-117 in PUJO specimens compared with controls. Our results show no clinical significance of the expression of neuronal markers in predicting degree of pre-operative renal pelvis dilation or differential renal function. The heterogeneity of expression of neuronal markers in PUJO specimens and controls in our population is at variance with prior studies. The etiology of PUJO is likely to be complex and multifactorial.
先天性肾盂输尿管连接部梗阻（PUJO）是新生儿肾积水最常见的病因之一。PUJ处的梗阻有潜在的严重不良后果，如肾损害。虽然肾盂成形术已被确立为确定性治疗方法，但先天性PUJO的确切病理生理学仍不清楚。最近的研究提出神经支配缺陷是先天性PUJO的一个病因。我们旨在研究与对照组相比，PUJO标本中各种神经标志物的表达情况，并评估术前肾脏疾病或功能障碍的严重程度是否与切除的PUJO标本中神经标志物的表达有关。
纳入2008年至2012年在新加坡KK妇女儿童医院因原发性PUJO接受离断性肾盂成形术的所有连续患者。排除合并其他肾脏病变的患者。对照组取自同期因肾母细胞瘤或其他良性肾脏疾病接受肾切除术的患者。标本用神经标志物蛋白基因产物9.5（PGP9.5）、突触素和S-100以及Cajal间质细胞标志物CD-117进行免疫组织化学染色（表）。由两名独立观察者与对照组相比，对标志物的表达水平进行半定量评估（降低、增加或无变化）。获取患者术前肾脏解剖学（肾盂大小的超声测量）和功能参数（使用MAG-3肾扫描测量的分肾功能）数据。
研究了38个PUJO标本（38个肾单位）和20个对照组。肾盂成形术时患者的平均年龄为25.3个月（2.9 - 167.6个月）。术前肾盂大小的中位数为25.0毫米（17.0 - 50.0毫米）。PUJO标本和对照组在神经支配分布上均表现出很大的异质性。所有四种免疫组织化学标志物均不能预测术前肾盂的明显扩张或手术肾脏术前肾功能的减退。
与对照组相比，PUJO标本中神经标志物突触素、PGP9.5、S-100和CD-117的表达存在显著差异。我们的结果表明，神经标志物的表达在预测术前肾盂扩张程度或分肾功能方面无临床意义。我们研究人群中PUJO标本和对照组神经标志物表达的异质性与先前的研究不同。PUJO的病因可能是复杂的多因素的。
