Ultrastructural and immunohistopathological evaluation of intravesical ureters via electron and light microscopy in children with vesicoureteral reflux.

ABSTRACT

PURPOSE: We used immunohistochemical methods and transmission electron microscopy to investigate the cytokine profiles and ultrastructural changes in the ureterovesical junction of children with primary vesicoureteral reflux. MATERIALS AND METHODS: A total of 39 distal intravesical ureters were obtained from 23 children who underwent ureteroneocystostomy for primary vesicoureteral reflux. Ureteral wall smooth muscle organization and transforming growth factor-ß1, vascular endothelial growth factor and CD34 were evaluated immunohistochemically and compared to controls, which consisted of 10 age matched autopsy specimens. Ultrastructural evaluations and morphological descriptions were performed semiquantitatively and compared to the published data. RESULTS: Of the patients 6 (26%) were male and 17 (74%) were female, and mean ± SD age was 73.2 ± 34.3 months (range 12 to 168). There was no correlation between reflux grade and age (p = 0.39). Smooth muscle disorganization score differed significantly between patients with intravesical ureters and controls (p = 0.01). Transforming growth factor-ß1 levels were significantly higher (p = 0.001) and vascular endothelial growth factor levels and microvessel densities were significantly lower in the patients with reflux compared to controls (both p <0.001). Vascular endothelial growth factor, CD34 and transforming growth factor-ß1 levels did not correlate with reflux grades (p = 0.84, p = 0.76 and p = 0.10, respectively). Urothelium, lamina propria and tunica adventitia appeared normal in the specimens for all grades of vesicoureteral reflux using transmission electron microscopy. Damage was observed in the muscular layers of the ureterovesical junction, especially in patients with grade IV or V reflux. CONCLUSIONS: Primary refluxing ureters exhibit immunohistopathological abnormalities compared to normal ureters irrespective of reflux grade, and ultrastructural changes are especially severe in cases of high grade reflux. These abnormalities can hinder the normal ureteral valve mechanism, and may lead to reflux due to smooth muscle dysfunction and microvascular alterations.