CLINICAL AND TRANSLATIONAL RESEARCH Cytomegalovirus Mismatch as Major Risk Factor for Delayed Graft Function After Pancreas Transplantation Manuel Maglione, 1 Matthias O. Biebl, 1 Hugo Bonatti, 2 Georg Go ¨bel, 3 Thomas Ratschiller, 1 Stefan Schneeberger, 1 Gerald Brandacher, 1 Paul Hengster, 1 Christian Margreiter, 1 Nicole Berger, 1 Raimund Margreiter, 1 Johann Pratschke, 1 and Walter Mark 1,4 Background. Risk factors for delayed graft function (DGF) in pancreas transplantation (PTx) and its implications on graft survival are poorly defined. Methods. Eighty-seven consecutive first-time PTx for type I diabetes performed between January 2003 and December 2007 were retrospectively reviewed. DGF was defined as a reversible need for exogenous insulin beyond postoperative day 10 (DGF group [DGFG]). For statistical analysis, DGFG patients were compared with patients with immediate graft function (control group [CG]). Results. DGF occurred in 16 patients (18.6%). C-peptide levels and DGF were inversely correlated (r=0.24, P=0.03). In univariate analysis, donor cytomegalovirus (CMV)+ antibody status, and D+/R- CMV mismatch were signifi- cantly associated with DGF (81.3% vs. CG 52.1%, P=0.029; and 62.5% vs. CG 21.1%, P=0.002, respectively). Com- pared with University of Wisconsin solution, histidine tryptophan ketoglutarate-preserved grafts displayed higher DGF rates (37.5% vs. CG 12.7%, P=0.030), similar to female recipients (DGFG 68.8% vs. CG 35.2%, P=0.015). On multi- variate analysis, a significantly higher DGF incidence was noted in female recipients (DGFG 68.8% vs. CG 35.2%; P=0.03) and in recipients with D+/R- CMV mismatch (DGFG 62.5% vs. CG 21.1%; P=0.03). With a median follow-up of 40.4 months (range 0.7–74.2), graft survival at 5 years did not differ between both groups (94.4% CG vs. 93.8% DGFG; P=0.791). Conclusion. This is the first study that identifies CMV mismatch (D+/R-) as an additional risk factor for DGF occurrence in PTx. In this particular cohort, DGF does not seem to affect graft survival. Keywords: Pancreas transplantation, Delayed graft function, Cytomegalovirus. (Transplantation 2010;90: 666–671) R ecent refinements in immunosuppression, antimicrobial prophylaxis, and therapy and surgical technique have im- proved outcome and broadened indications for transplanta- tion, thus widening the gap between demand for and supply of solid organ grafts. To counteract this development, it be- came evident that the donor pool needed to be expanded by extending donor criteria. Extended criteria donors have been defined for kidney transplantation. Similar criteria have also been proposed for liver transplantation (1, 2), including ad- vanced age, morbid obesity, extended intensive care unit stay, and use of high-dose catecholamines. Furthermore, manifest infection and non-heart beating donation may qualify donors for extended criteria donors. In pancreas transplantation (PTx), such criteria are not well established. This is partially because of the fact that pancreatic transplantation is not a life saving procedure, and there is genuine reluctance to use or- gans that may not function well or even develop graft pancre- atitis. However, in some regions, there is a high demand for pancreatic allografts, and specialized centers have started to use grafts, which traditionally would have been discarded be- cause of inadequate quality. Between 1994 and 2007, the proportion of cadaveric donors aged more than 55 years increased from 20% to 38.5% in the Eurotransplant region (3). Advanced donor age is one of the most important factors for susceptibility to ischemic injury of grafts. In addition, natural aging of the parenchyma with degeneration of vascularity in conjunction with in- M.M. and M.O.B. contributed equally to this study. 1 Center for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria. 2 University of Virginia Health Service, Department of Surgery, Charlottes- ville, Virginia. 3 Department for Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria. 4 Address correspondence to: Walter Mark, M.D., Center for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail: walter.mark@i-med.ac.at M.M. and M.B. conceived and designed the study, did the statistical analysis, and wrote the manuscript; H.B., T.R., C.M., and N.B. contributed to acquisition and analysis of data; G.G. contributed substantially to statis- tical analysis; S.S., G.B., and P.H. helped in collecting the data; W.M. did the majority of transplants; and R.M. and J.P. critically revised and finally approved the article. Received 20 November 2009. Revision requested 5 January 2010. Accepted 28 May 2010. Copyright © 2010 by Lippincott Williams & Wilkins ISSN 0041-1337/10/9006-666 DOI: 10.1097/TP.0b013e3181ea67a1 666 | www.transplantjournal.com Transplantation • Volume 90, Number 6, September 27, 2010