Pancreas allograft rejection
- Tarek Alhamad, MD, MS, FACP, FASN
Tarek Alhamad, MD, MS, FACP, FASN
- Assistant Professor of Medicine
- Washington University School of Medicine
- Aleksandra Kukla, MD
Aleksandra Kukla, MD
- Associate Professor of Medicine
- University of Minnesota
- Robert J Stratta, MD
Robert J Stratta, MD
- Professor of Surgery, Director of Transplantation
- Wake Forest School of Medicine
- Section Editors
- Daniel C Brennan, MD, FACP
Daniel C Brennan, MD, FACP
- Editor-in-Chief — Nephrology
- Section Editor — Renal Transplantation
- Professor of Medicine
- Washington University School of Medicine
- David M Nathan, MD
David M Nathan, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Diabetes Mellitus
- Professor of Medicine
- Harvard Medical School
The outcomes of vascularized pancreas transplantation have steadily improved secondary to improvements in surgical techniques, donor and recipient selection and management, and diagnostic imaging, all of which have resulted in a reduction in early technical graft losses. In addition, advances in immunosuppression and immune monitoring have led to a commensurate decrease in immunological graft losses. However, pancreas allograft rejection remains a major clinical challenge and is the primary cause of death-censored pancreas allograft loss after three months posttransplant.
At present, approximately three-quarters of pancreas transplants in the United States are performed as simultaneous pancreas-kidney (SPK) transplants, with the remainder performed as either sequential pancreas after kidney transplant (PAK, 16 percent) or pancreas transplants alone (PTA, 9 percent) .
This topic reviews the epidemiology, clinical presentation, diagnosis, treatment, and prognosis of acute rejection of the pancreas allograft in the setting of SPK transplantation. However, this discussion is also applicable to pancreas allograft rejection in PAK and PTA recipients.
The selection of patients, induction, and maintenance immunosuppressive therapies are discussed elsewhere. (See "Patient selection for and immunologic issues relating to kidney-pancreas transplantation in diabetes mellitus".)
The benefits and complications (other than rejection) associated with these procedures and the roles of PTA and islet transplantation in diabetic patients without renal failure are discussed separately. (See "Benefits and complications associated with kidney-pancreas transplantation in diabetes mellitus" and "Pancreas and islet transplantation in diabetes mellitus".)
- Kandaswamy R, Skeans MA, Gustafson SK, et al. Pancreas. Am J Transplant 2016; 16 Suppl 2:47.
- Niederhaus SV, Leverson GE, Lorentzen DF, et al. Acute cellular and antibody-mediated rejection of the pancreas allograft: incidence, risk factors and outcomes. Am J Transplant 2013; 13:2945.
- Dong M, Parsaik AK, Kremers W, et al. Acute pancreas allograft rejection is associated with increased risk of graft failure in pancreas transplantation. Am J Transplant 2013; 13:1019.
- Kandaswamy R, Skeans MA, Gustafson SK, et al. OPTN/SRTR 2013 Annual Data Report: pancreas. Am J Transplant 2015; 15 Suppl 2:1.
- Rudolph EN, Dunn TB, Mauer D, et al. HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival. Am J Transplant 2016; 16:2401.
- Malheiro J, Martins LS, Tafulo S, et al. Impact of de novo donor-specific anti-HLA antibodies on grafts outcomes in simultaneous pancreas-kidney transplantation. Transpl Int 2016; 29:173.
- Mittal S, Page SL, Friend PJ, et al. De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure. Am J Transplant 2014; 14:1664.
- Cantarovich D, De Amicis S, Akl A, et al. Posttransplant donor-specific anti-HLA antibodies negatively impact pancreas transplantation outcome. Am J Transplant 2011; 11:2737.
- Mujtaba MA, Fridell JA, Higgins N, et al. Early findings of prospective anti-HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience. Clin Transplant 2012; 26:E492.
- Mujtaba MA, Fridell J, Book B, et al. Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies. Clin Transplant 2015; 29:991.
- Martins L, Malheiro J, Henriques AC, et al. Pancreas-kidney transplantation and the evolution of pancreatic autoantibodies. Transplant Proc 2009; 41:913.
- Papadimitriou JC, Drachenberg CB, Wiland A, et al. Histologic grading of acute allograft rejection in pancreas needle biopsy: correlation to serum enzymes, glycemia, and response to immunosuppressive treatment. Transplantation 1998; 66:1741.
- Shapiro R, Jordan ML, Scantlebury VP, et al. Renal allograft rejection with normal renal function in simultaneous kidney/pancreas recipients: does dissynchronous rejection really exist? Transplantation 2000; 69:440.
- Troxell ML, Koslin DB, Norman D, et al. Pancreas allograft rejection: analysis of concurrent renal allograft biopsies and posttherapy follow-up biopsies. Transplantation 2010; 90:75.
- Klassen DK, Hoen-Saric EW, Weir MR, et al. Isolated pancreas rejection in combined kidney pancreas tranplantation. Transplantation 1996; 61:974.
- Gill IS, Stratta RJ, Taylor RJ, et al. Correlation of serologic and urinary tests with allograft biopsy in the diagnosis of pancreas rejection. Transplant Proc 1997; 29:673.
- Mittal S, Nagendran M, Franklin RH, et al. Postoperative impaired glucose tolerance is an early predictor of pancreas graft failure. Diabetologia 2014; 57:2076.
- Allen RD, Wilson TG, Grierson JM, et al. Percutaneous biopsy of bladder-drained pancreas transplants. Transplantation 1991; 51:1213.
- Klassen DK, Weir MR, Cangro CB, et al. Pancreas allograft biopsy: safety of percutaneous biopsy-results of a large experience. Transplantation 2002; 73:553.
- Redfield RR, Kaufman DB, Odorico JS. Diagnosis and Treatment of Pancreas Rejection. Curr Transplant Rep 2015; 2:169.
- Margreiter C, Aigner F, Resch T, et al. Enteroscopic biopsies in the management of pancreas transplants: a proof of concept study for a novel monitoring tool. Transplantation 2012; 93:207.
- Nakhleh RE, Benedetti E, Gruessner A, et al. Cystoscopic biopsies in pancreaticoduodenal transplantation. Are duodenal biopsies indicative of pancreas dysfunction? Transplantation 1995; 60:541.
- Carbajal R, Karam G, Renaudin K, et al. Specific humoral rejection of a pancreas allograft in a recipient of pancreas after kidney transplantation. Nephrol Dial Transplant 2007; 22:942.
- Drachenberg CB, Torrealba JR, Nankivell BJ, et al. Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema. Am J Transplant 2011; 11:1792.
- Hawthorne WJ, Griffin AD, Lau H, et al. Experimental hyperacute rejection in pancreas allotransplants. Transplantation 1996; 62:324.
- Torrealba JR, Samaniego M, Pascual J, et al. C4d-positive interacinar capillaries correlates with donor-specific antibody-mediated rejection in pancreas allografts. Transplantation 2008; 86:1849.
- Pascual J, Samaniego MD, Torrealba JR, et al. Antibody-mediated rejection of the kidney after simultaneous pancreas-kidney transplantation. J Am Soc Nephrol 2008; 19:812.
- de Kort H, Munivenkatappa RB, Berger SP, et al. Pancreas allograft biopsies with positive c4d staining and anti-donor antibodies related to worse outcome for patients. Am J Transplant 2010; 10:1660.
- Melcher ML, Olson JL, Baxter-Lowe LA, et al. Antibody-mediated rejection of a pancreas allograft. Am J Transplant 2006; 6:423.
- Munivenkatappa RB, Philosophe B, Papadimitriou JC, Drachenberg CB. Interacinar c4d staining in pancreas allografts. Transplantation 2009; 88:145.
- Khwaja K, Wijkstrom M, Gruessner A, et al. Pancreas transplantation in crossmatch-positive recipients. Clin Transplant 2003; 17:242.
- Reddy KS, Davies D, Ormond D, et al. Impact of acute rejection episodes on long-term graft survival following simultaneous kidney-pancreas transplantation. Am J Transplant 2003; 3:439.
- Tesi RJ, Henry ML, Elkhammas EA, et al. The frequency of rejection episodes after combined kidney-pancreas transplant--the impact on graft survival. Transplantation 1994; 58:424.
- Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin Transplant 2005; 19:433.
- Morel P, Brayman KL, Goetz FC, et al. Long-term metabolic function of pancreas transplants and influence of rejection episodes. Transplantation 1991; 51:990.
- Prieto M, Sutherland DE, Goetz FC, et al. Pancreas transplant results according to the technique of duct management: bladder versus enteric drainage. Surgery 1987; 102:680.
- Benedetti E, Najarian JS, Gruessner AC, et al. Correlation between cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants. Surgery 1995; 118:864.
- EPIDEMIOLOGY AND RISK FACTORS
- EVALUATION AND DIAGNOSIS
- Clinical manifestations
- Laboratory monitoring for allograft rejection
- Diagnosis of pancreas allograft rejection
- - When to suspect pancreas allograft rejection
- Approach to the diagnosis of pancreas allograft rejection
- - Patients with a PAK or PTA
- - Patients with a SPK transplant
- Confirming the diagnosis of pancreas allograft rejection
- - Acute cellular rejection
- - Antibody-mediated rejection
- - Mixed acute rejection
- Differential diagnosis
- Our approach to treatment
- Patients with biopsy-proven rejection
- - Patients with acute cellular rejection
- - Patients with antibody-mediated rejection
- - Patients with mixed acute rejection
- Patients with suspected (but not biopsy-proven) rejection
- Monitoring after treatment for rejection
- SUMMARY AND RECOMMENDATIONS