title: Successful Porcine Renal Transplantation After 60 Minutes of Donor Warm Ischemia: Extracorporeal Perfusion and Thrombolytics.
abstract: Donation from uncontrolled circulatory determination of death donors (uDCD) is impractical in United States because of the time needed to organize procurement before irreversible organ damage. Salvaging organs after prolonged warm ischemic time (WIT) may address this limitation. We evaluated the combination of extracorporeal support (ECS) and thrombolytics in a porcine uDCD renal transplant model. Nonanticoagulated uDCD sustained 60 min of WIT, and two groups were studied. Rapid recovery (RR)-uDCD renal grafts procured using the standard quick topical cooling and renal flush, and ECS-assisted donation (E-uDCD), 4 hr ECS plus thrombolytics for in situ perfusion before procurement. All kidneys were flushed and cold stored, followed by transplantation into healthy nephrectomized recipients without immunosuppression. Delayed graft function (DGF) was defined as creatinine more than 5.0 mg/dl on any postoperative day. Twelve kidneys in E-uDCD and 6 in RR-uDCD group were transplanted. All 12 E-uDCD recipients had urine production and adequate function in the first 48 hr, but two grafts (16.7%) had DGF at 96 hr. All six recipients from RR-uDCD group had DGF at 48 hr and were killed. Creatinine and blood urea nitrogen (BUN) levels were significantly lower in E-uDCD compared with RR-uDCD group at 24 hr (2.9 ± 0.7 mg/dl vs. 5.2 ± 0.9 mg/dl) and 48 hr (3.2 ± 0.9 mg/dl vs. 7.2 ± 1.0 mg/dl); BUN levels at 24 and 48 hr were 28.3 ± 6.7 mg/dl vs. 39.5 ± 7.5 mg/dl and 23.9 ± 5.0 mg/dl vs. 46 ± 12.9 mg/dl, respectively. Thrombolytics plus ECS precondition organs in situ yielding functional kidneys in a porcine model of uDCD with 60 min of WIT. This procurement method addresses logistical limitations for uDCD use in the United States and could have a major impact on the organ donor pool.
authors: From the *Department of General Surgery, Henry Ford Health Systems, Detroit, Michigan; †Department of Surgery, Extracorporeal Life Support Laboratory, University of Michigan, Ann Arbor, Michigan; ‡Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; §Michigan Critical Care Consultants, Corp. Ann Arbor, Michigan; and ¶Department of Surgery, Section of Transplantation, University of Michigan, Michigan.
authors: David S
authors: DS
authors: Demos
authors: Amit
authors: A
authors: Iyengar
authors: Benjamin S
authors: BS
authors: Bryner
authors: Brian W
authors: BW
authors: Gray
authors: Hayley R
authors: HR
authors: Hoffman
authors: Marie S
authors: MS
authors: Cornell
authors: John E
authors: JE
authors: Wilkinson
authors: Daniel E
authors: DE
authors: Mazur
authors: Robert H
authors: RH
authors: Bartlett
authors: Jeffrey D
authors: JD
authors: Punch
authors: Alvaro
authors: A
authors: Rojas-Peña
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007668:Kidney / Q000098:blood supply*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000379:methods*; D034421:Sus scrofa; D013997:Time Factors; D014019:Tissue Donors / Q000600:supply & distribution; D052096:Warm Ischemia / Q000379:methods*