Are There Any Differences in the Neural and Extracellular Matrix Proteins Density Between Children and Adults with Intrinsic Ureteropelvic Junction Obstruction (original) (raw)
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Journal of Pediatrics Review, 2016
Context: Ureteropelvic junction obstruction (UPJO) is the most common obstructive disease of the urinary tract in infancy and childhood with a prevalence of 15%-45% in neonates with antenatal hydronephrosis. The diagnosis of UPJO should be confirmed by imaging studies-most of which have a propensity to radiation exposure. Objectives: The current study aimed to present a review protocol to assess the role of measuring urinary biomarkers to distinguish severe UPJO from milder forms of the disease. Data Sources: The database of UPJO studies was searched and studies that compared the levels of urinary biomarkers with the gold standard (i e, dynamic renal scans) for UPJO diagnosis were selected. Severity assessment was done quantitatively. Study Selection: Three hundred fifty-eight articles were identified across the electronic databases. Twenty-seven articles were selected for the final analyses. Data Extraction: Data were extracted independently by three reviewers and analyzed using STATA software version 12. Results: Meta-analysis of studies showed that patients with severe UPJO had significantly higher biomarker levels than those with mild to moderate obstruction, with a pooled standardized mean difference (SMD) of 0.5 (confidence interval (CI) 95%, 0.34-0.67; P < 0.001); and significantly higher biomarker standardized to urinary creatinine levels than those with mild to moderate obstruction, with a pooled SMD of 1.02 (95% CI, 0.88-1.16; P < 0.001). Meta-analysis showed that patients with severe UPJO had significantly higher biomarker levels than healthy children, with a pooled SMD of 1.27 (CI 95%, 1.16-1.39; P < 0.001); and significantly higher biomarker standardized to urinary creatinine levels than healthy children, with a pooled SMD of 1.14 (CI 95%, 0.95-1.32; P < 0.001). Conclusions: The assessment of urinary biomarkers is a helpful tool to assess the presence and severity of UPJO, but there is little published data on each of the studied biomarkers. It is suggested to perform future larger multicenter studies.
EXTRACELLULAR MATRIX DEGRADATION AND REDUCED NEURAL DENSITY IN CHILDREN WITH UPJ OBSTRUCTION
The Journal of Urology, 2008
To investigate the extracellular matrix microenvironment and nerve supply of ureteropelvic junctions (UPJs) in children with intrinsic UPJ obstruction. Congenital UPJ obstruction is the most common cause of neonatal hydronephrosis. Although many studies investigating the molecular changes within this segment have been performed, the underlying mechanisms of UPJ obstruction are still unclear.
Int J Exp Pathol, 2010
Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation ⁄ apoptosis, renin-angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major shortcoming is the absence of data on the impact of UPJ obstruction on long-term adult renal function to elucidate whether these animal data are also valid in humans.
EXTRACELLULAR MATRIX DEGRADATION AND REDUCED NERVE SUPPLY IN REFLUXING URETERAL ENDINGS
Journal of Urology, 2004
To investigate the extracellular matrix microenvironment and nerve supply of ureteropelvic junctions (UPJs) in children with intrinsic UPJ obstruction. Congenital UPJ obstruction is the most common cause of neonatal hydronephrosis. Although many studies investigating the molecular changes within this segment have been performed, the underlying mechanisms of UPJ obstruction are still unclear.
Journal of pediatric surgery, 2006
Studies of children with urinary flow impairment (UFI) at the ureteropelvic junction (UPJ) have revealed prestenotic, stenotic, and poststenotic histologic changes. Muscle function, however, has not been investigated. We therefore evaluated in vitro UPJ contractility by tensiometry in children with UFI. Freshly excised UPJs from 11 children with UFI (6 functional, 5 obstructive) were each divided into 3 parallel, prestenotic, stenotic, and poststenotic rings, and those from 7 children with Wilms' tumor were divided into proximal, medial, and distal segments. Each ring was studied in vitro by tensiometry in the basal state and after stimulation with 25 and 60 mmol/L KCl. The stenotic rings from the UFI subjects displayed a significantly lower basal contractility than the other 2 rings, and their 25 and 60 mmol/L KCl-induced contractility was absent or severely reduced, whereas the values of these parameters were similar to that observed in controls in the other 2 rings of patient...
Structural changes of smooth muscle in congenital ureteropelvic junction obstruction
Journal of Pediatric Surgery, 2005
Background/Purpose: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Previous studies have reported that the excess amount of collagen restricting mobility and resiliency of the UPJ is the result of an impaired collagen production by anomalous smooth muscle cells (SMCs). Our purpose was to evaluate the role of SMC differentiation in the pathogenesis of UPJ obstruction. Methods: Surgical specimens of UPJ from 21 patients (8 girls/13 boys) who were subjected to dismembered pyeloplasty were examined immunohistochemically using monoclonal antibodies against smooth muscle (SM) myosin heavy chain isoforms including SM1, SM2, and SMemb. The age ranged from 1 month to 13 years. Ureteropelvic walls taken from 14 forensic autopsy cases, with no urological abnormalities, served as age-matched control group. Results: The immunohistochemical expression of SM1 and SM2 in UPJ obstruction was significantly increased when compared with controls ( P b .05). In contrast, there was no statistical difference of expression of SMemb. Conclusion: Our findings supported the hypothesis that the primary anomaly in UPJ obstruction may be attributed to a malfunction of SMCs in the ureter. D
International Urology and Nephrology, 2011
Purpose The authors examined the number of interstitial cells of Cajal-like cells (ICC-LCs) in obstructed ureteropelvic junction (UPJ) in comparison with normal UPJ specimens and age-related changes. Materials and methods A total of 20 human formalin fixed, paraffin-embedded specimens of intrinsic UPJO from children at the mean age of 8.1 years (age range: 8 months-16.8 years) and 5 control samples from children at the mean age of 2.3 years (range 2.4 months-7.4 years) were investigated immunohistochemically for the expression of c-kit proto-oncogene by light microscopy with computerized image analysis. The results were examined by Fisher's exact test, Yates' chi-square test, and t test for Pearson's correlation coefficient. A P value less than 0.05 was considered statistically significant. Results The number of ICC-LCs-dense fields was significantly higher in UPJO specimens in comparison with the normal group (P = 0.0004). The number of ICC-LCs-sparse fields was significantly lowered in UPJO specimens in comparison with the normal group (P = 0.0122). There was no significant difference in the number of ICC-LCs-medium fields in obstructed and normal UPJ specimens. The number of ICC-LCs was decreasing significantly with increasing age of the patients with UPJO (P = 0.0038). Conclusions The higher density of c-kit-positive ICC-LCs in UPJ may manifest the compensation of altered peristalsis in UPJO. The number of ICC-LCs-dense fields decreasing with age may show the failure of compensation and regression of the compensatory changes. Keywords c-kit Á Child Á Interstitial cells of Cajallike Á Obstruction Á Peristalsis Á Ureteropelvic junction Ureteropelvic junction obstruction (UPJO) is regarded as the most common congenital abnormality of the ureter. According to Murnagham, the cause of the obstruction is the abnormality in the lamina muscularis of UPJ, whereas Notley and Hanna point to the
Journal of Pediatric Urology, 2010
To investigate histopathological changes in ureteropelvic junction obstruction (UPJO) from an etiological perspective. Medical records of patients with UPJO were reviewed and pathological specimens collected. Nephrectomy materials from forensic autopsies were taken as controls. Specimens were assessed with light microscopy. Fibronectin, type 4 collagen, laminin, Bax and Bcl-2 expression for apoptosis, together with interstitial cells of Cajal determination with c-kit were determined immunohistochemically. Staining scores were evaluated semiquantitatively. Results were evaluated using Mann-Whitney U-test. Control group comprised 14 children (median age, 3.5 years; 6 months-17 years). Study group comprised 22 children with UPJO (median age, 9 months; 1 month-10 years). Light microscopy revealed non-specific inflammation, epithelial proliferation and atrophy with fibrosis in the smooth muscle of the UPJ in all patients. Fibronectin, type 4 collagen and laminin were found to be significantly increased in UPJO at the intrafascicular space of smooth muscle and the matrix of stroma. Bcl-2 expression was increased in UPJO. c-Kit was unable to stain interstitial cells of Cajal, but staining for mast cells was significant. High expression of fibronectin, laminin and type 4 collagen may indicate a relation to the pathogenesis of UPJO. Defective kidney morphogenesis, during branching and tubulogenesis of ureteric bud, may be responsible for this congenital pathology.
Kidney International, 2006
The renal histologic changes associated with congenital ureteropelvic junction obstruction (UPJO) and the relationship to clinical imaging have not been well studied. In order to better understand the histologic alterations of congenital UPJO and their relationship with clinical imaging and outcomes, we examined renal biopsies from 61 patients undergoing pyeloplasty for congenital UPJO. Glomeruli were analyzed for various injury patterns and the tubulointerstitium was examined for tubular atrophy/simplification and fibrosis. Two methods were used to evaluate tubular mass: glomerular density and morphometric measurement of tubular size and density. Control specimens were obtained from age-matched autopsy specimens without renal pathology. Glomerular changes were identified in 73% of all biopsies and were present in a range from 1.7 to 91% of glomeruli in each patient. Overt tubulointerstitial changes were present in 26% of all biopsies. Fibrosis was noted to occur with tubulointerstitial changes in a significantly greater fraction of children over the age of 1 year (P ¼ 0.026). Increased glomerular density was associated with severe hydronephrosis (Po0.02). Normal glomerular density was inversely correlated with age (Po0.001), but this relationship was more variable in UPJO (Po0.01). Among patients with intact differential function preoperatively (445%), postoperative functional decline was predicted only by increased glomerular density. 20 biopsies without overt tubulointerstitial changes were analyzed morphometrically and showed a significant reduction in proximal tubular (PT) size, but unchanged density. Distal tubular (DT) size was unchanged in UPJO, but density was increased. The PT/DT ratio was therefore markedly decreased in UPJO (Po0.0001). Both PT and DT sizes were significantly larger in children with a diuretic renogram washout time less than 20 min than those with greater than 20 min, a common threshold for functionally significant obstruction (Po0.05). Capsular thickness was significantly increased in UPJO. In all, 36% of biopsies had a thickness 40.5 mm and this was associated with greater degrees of tubulointerstitial changes and glomerular alterations. Congenital UPJO produces a variety of renal parenchymal changes, which may in part reflect abnormal development. Some of these alternations are seen in clinical imaging and may help predict outcomes, but there is significant discordance between conventional imaging and histological findings.