Ex vivo ureteroscopic treatment of calculi in donor kidneys at renal transplantation.

PURPOSE: We evaluated the safety and efficacy of ex vivo ureteroscopy (ExURS) as a means of rendering the donated kidney stone-free at live donor renal transplantation. MATERIALS AND METHODS: A total of 10 suitable kidney donors with small, unilateral nonobstructive calculi underwent live donor nephrectomy (8 open flank, 2 hand assisted transperitoneal). Immediately after cold perfusion, ExURS was performed in an iced saline solution. Access to the collecting system was via the ureteral stump. Calculi were either removed with endoscopic baskets and/or completely fragmented with Holmium laser lithotripsy. RESULTS: Access to the renal collecting system was technically successful in all cases. A total of 10 stones, ranging in largest diameter from 1 to 8 mm (average 5.2) were visualized. Of the kidneys 6 had solitary stones, 2 had 2 stones and 1 had no stone. Of 10 stones 9 were successfully removed and/or fragmented with an average procedure time of 6.5 minutes (range 3 to 28). Indwelling ureteral stents were placed at transplantation in 5 of 10 kidneys. There were no intra-operative or postoperative ureteral complications. At 1 month after transplant serum creatinine ranged from 0.9 to 2.7 mg/dl (average 1.5). At a mean followup of 33.2 months new stones have not formed in any recipients and at mean 36.4-month followup no new calculi have formed in the remaining kidney of any donors. CONCLUSIONS: ExURS is a technically feasible means of rendering a stone bearing kidney stone-free without compromising ureteral integrity or renal allograft function.

The role of calpain in the proteolytic cleavage of E-cadherin in prostate and mammary epithelial cells.

The E-cadherin protein mediates Ca(2+)-dependent interepithelial adhesion. Association of E-cadherin with the catenin family of proteins is critical for the maintenance of a functional adhesive complex. We have identified a novel truncated E-cadherin species of 100-kDa (E-cad(100)) in prostate and mammary epithelial cells. E-cad(100) was generated by treatment of cells with ionomycin or TPA. Cell-permeable calpain inhibitors prevented E-cad(100) induction by ionomycin. Immunoblotting for spectrin and mu-calpain confirmed calpain activation in response to ionomycin treatment. Both the mu- and m-isoforms of calpain efficiently generated E-cad(100) in vitro. The E-cad(100) fragment was unable to bind to beta-catenin, gamma-catenin, and p120, suggesting that this cleavage event would disrupt the E-cadherin adhesion complex. Mutational analysis localized the calpain cleavage site to the cytosolic domain upstream of the beta- and gamma-catenin binding motifs of E-cadherin. Because E-cadherin is inactivated in many adenocarcinomas we hypothesized that calpain may play a role in prostate tumorigenesis. A prostate cDNA microarray data base was analyzed for calpain expression in which it was found that m-calpain was up-regulated in localized prostate cancer, and to an even higher degree in metastatic prostate cancer compared with normal prostate tissue. Furthermore, we examined the cleavage of E-cadherin in prostate cancer specimens and found that E-cad(100) accumulated in both localized and metastatic prostate tumors, supporting the cDNA microarray data. These findings demonstrate a novel mechanism by which E-cadherin is functionally inactivated through calpain-mediated proteolysis and suggests that E-cadherin is targeted by calpain during the tumorigenic progression of prostate cancer.