Altered 'active' antireflux mechanism in primary vesico-ureteric reflux: a morphological and manometric study

OBJECTIVE: To immunolocate c-kit-positive interstitial cells of Cajal (ICCs, known to be responsible for pacemaker activity in human ureters, coordinating ureteric motility) in the intramural ureter of patients with different grades of vesico-ureteric reflux (VUR), to assess the ureteric histology and correlate these findings with manometric patterns. PATIENTS AND METHODS: The VU junction (VUJ) represents the boundary between the low-pressure of the upper and high pressure of the lower urinary tract, protecting the upper tract from VUR using active and passive antireflux mechanisms. The contraction of the longitudinal muscle coat of the VUJ possibly functions as an 'active' antireflux system, but previous manometric findings on refluxing ureteric units (RUs) have shown altered patterns. In all, 32 RU ends were stained using both picro-Mallory and Sirius Red techniques; in a parallel immunohistochemical procedure, using mast cell tryptase and CD117 antibodies (to identify ICCs), they were compared with eight control ureteric ends. Ureteric manometry of the VUJ was also done during ureteric reimplantation. RESULTS: The histochemical and immunohistochemical results in the RUs showed a replacement of the altered smooth muscle fascicles by collagenous stroma and significant loss of ICCs in RU ends, both correlated with the grade of VUR. Ureteric manometry showed significant impairment of basal and maximum pressure in RUs, correlated, respectively, with histological lesions and loss of ICCs. CONCLUSION: Deficiency of the longitudinal muscle coat probably leads to dysfunction and insufficiency of the ostial valve mechanism, with subsequent impairment of the active valve mechanism. Histological, histochemical and immunohistochemical changes support the alterations of ureteric peristalsis in RUs.