Ureteral replacement using small-intestinal submucosa and a collagen inhibitor in a porcine model

Small-intestinal submucosa (SIS) has been successful as an onlay graft in ureteral repair, but tubularized segment interposition of SIS has been unsuccessful. Our objective was to evaluate whether a type I collagen inhibitor, halofuginone, would prevent stricture formation in tubularized SIS interposition. We performed either laparoscopic partial ureteral excision followed by an SIS onlay graft (N = 5) or complete laparoscopic ureteral excision followed by an SIS interposition graft (N = 7) in domestic pigs. Animals received either no (N = 3), low-dose (N = 5), or high-dose (N = 4) halofuginone. Animals had ureteral stenting for 2 weeks after surgery and were permitted to survive for 6 or 9 weeks. An intravenous urogram (IVU) was performed prior to sacrifice. Kidneys were examined grossly and histologically. One animal that received an onlay graft died of an unrelated illness. The remaining four ureteral onlay animals, including one control and two low-dose and one high-dose pig, had grossly normal kidneys at harvest. The IVU was normal in the control and high-dose animal but showed delayed excretion with mild hydroureteronephrosis in the low-dose animals. Pathologic examination of the SIS site revealed circumferential reepithelialization with inflammation and mild fibrosis. All seven tubularized interposition graft kidneys demonstrated either severe hydroureteronephrosis (N = 5) or renal atrophy (N = 2), and all had complete obstruction on IVU. Pathologic examination revealed a stenotic ureteral lumen with extensive surrounding inflammation and fibrosis. An SIS onlay graft was successful in the porcine model of ureteral injury. Halofuginone, a type I collagen inhibitor, did not demonstrate a significant beneficial effect in this technique. Ureteral tubularized interpositions with SIS are unsuccessful and not improved by halofuginone.