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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Induction and Immunosuppressive Management of Pancreas Transplant Recipients

Author(s): Gabriella Amorese, Carlo Lombardo, Antonella Tudisco, Sara Iacopi, Francesca Menonna, Piero Marchetti, Fabio Vistoli and Ugo Boggi*

Volume 26, Issue 28, 2020

Page: [3425 - 3439] Pages: 15

DOI: 10.2174/1381612826666200430111620

Price: $65

Abstract

Background: Despite improved overall outcomes, rejection continues to occur frequently after pancreas transplantation.

Objective: To review the literature and to provide a state-of-the-art assessment of current practice and developments of immunosuppressive regimens in pancreas transplantation.

Methods: The literature was reviewed and relevant articles were retrieved and analyzed.

Results: Induction therapy is used in approximately 90% of the transplants, with T-cell depleting antibodies being the prevalent therapy (>90%). Despite the initial enthusiasm on steroid-free regimens, maintenance protocols continue to be mostly based on a combination of steroids, tacrolimus, and mycophenolate mofetil. Tacrolimus is used in the majority of recipients. Sirolimus is rarely used at the time of transplant and is introduced later on in approximately 10% of the recipients, mostly in the context of a switching strategy to address the side effects of calcineurin inhibitors. The overall quality of published studies was quite low, because of the retrospective design, the heterogeneity of study groups with respect to PTx categories, the inclusion of mixed recipient categories with respect to immunologic risk profile, and the use of non-standardized concurrent immunosuppressive therapies. In addition, most reported studies were clearly underpowered, and treatment outcomes were not standardized.

Conclusion: Since approximately two decades, immunosuppression in pancreas transplantation mostly consists of induction with depleting antibodies and maintenance therapy using a combination of steroids, tacrolimus, and mycophenolate mofetil. While true novelty would be very much needed, this review confirms the wide use and the clinical efficacy of this regimen.

Keywords: Pancreas transplantation, immunosuppression, acute rejection, chronic rejection, graft survival, patient survival, autoimmune recurrence, adverse events.

« Previous Next »
[1]
Boggi U, Vistoli F, Egidi FM, et al. Transplantation of the pancreas. Curr Diab Rep 2012; 12(5): 568-79.
[http://dx.doi.org/10.1007/s11892-012-0293-4] [PMID: 22828824]
[2]
Coppelli A, Giannarelli R, Vistoli F, et al. The beneficial effects of pancreas transplant alone on diabetic nephropathy. Diabetes Care 2005; 28(6): 1366-70.
[http://dx.doi.org/10.2337/diacare.28.6.1366] [PMID: 15920053]
[3]
Lombardo C, Perrone VG, Amorese G, et al. Update on pancreatic transplantation on the management of diabetes. Minerva Med 2017; 108(5): 405-18.
[PMID: 28466634]
[4]
Niclauss N, Morel P, Berney T. Has the gap between pancreas and islet transplantation closed? Transplantation 2014; 98(6): 593-9.
[http://dx.doi.org/10.1097/TP.0000000000000288] [PMID: 25029387]
[5]
Moassesfar S, Masharani U, Frassetto LA, et al. A comparative analysis of the safety, efficacy, and cost of islet versus pancreas transplantation in nonuremic patients with type 1 diabetes. Am J Transplant 2016; 16(2): 518-26.
[http://dx.doi.org/10.1111/ajt.13536] [PMID: 26595767]
[6]
Occhipinti M, Lampasona V, Vistoli F, et al. Zinc transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant. Transplantation 2011; 92(6): 674-7.
[http://dx.doi.org/10.1097/TP.0b013e31822ae65f] [PMID: 21792090]
[7]
Vendrame F, Pileggi A, Laughlin E, et al. Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation, despite immunosuppression, is associated with autoantibodies and pathogenic autoreactive CD4 T-cells. Diabetes 2010; 59(4): 947-57.
[http://dx.doi.org/10.2337/db09-0498] [PMID: 20086230]
[8]
Fioretto P, Najafian B, Sutherland DE, Mauer M. Tacrolimus and cyclosporine nephrotoxicity in native kidneys of pancreas transplant recipients. Clin J Am Soc Nephrol 2011; 6(1): 101-6.
[http://dx.doi.org/10.2215/CJN.03850510] [PMID: 21051744]
[9]
Ekberg H, van Gelder T, Kaplan B, Bernasconi C. Relationship of tacrolimus exposure and mycophenolate mofetil dose with renal function after renal transplantation. Transplantation 2011; 92(1): 82-7.
[http://dx.doi.org/10.1097/TP.0b013e31821fad06] [PMID: 21562449]
[10]
Richards KR, Hager D, Muth B, Astor BC, Kaufman D, Djamali A. Tacrolimus trough level at discharge predicts acute rejection in moderately sensitized renal transplant recipients. Transplantation 2014; 97(10): 986-91.
[http://dx.doi.org/10.1097/TP.0000000000000149] [PMID: 24784360]
[11]
Stratta RJ, Sollinger HW, Perlman SB, et al. Early diagnosis and treatment of pancreas allograft rejection. Transpl Int 1988; 1(1): 6-12.
[http://dx.doi.org/10.1111/j.1432-2277.1988.tb01772.x] [PMID: 2473766]
[12]
Gruessner AC, Gruessner RW. Pancreas transplantation of US and non-US cases from 2005 to 2014 as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR). Rev Diabet Stud 2016; 13(1): 35-58.
[http://dx.doi.org/10.1900/RDS.2016.13.35] [PMID: 26982345]
[13]
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(8): 2401-12.
[http://dx.doi.org/10.1111/ajt.13734] [PMID: 26814363]
[14]
Huh KH, Kim MS, Kim HJ, et al. Renal transplantation in sensitized recipients with positive luminex and negative CDC (complement-dependent cytotoxicity) crossmatches. Transpl Int 2012; 25(11): 1131-7.
[http://dx.doi.org/10.1111/j.1432-2277.2012.01543.x] [PMID: 22897830]
[15]
Ringers J, van der Torren CR, van de Linde P, et al. Pretransplantation GAD-autoantibody status to guide prophylactic antibody induction therapy in simultaneous pancreas and kidney transplantation. Transplantation 2013; 96(8): 745-52.
[http://dx.doi.org/10.1097/TP.0b013e3182a012cc] [PMID: 23912172]
[16]
Gruessner RWG. Immunobiology, diagnosis, and treatment of pancreas graft rejection Transplantation of the pancreas Verlag New York. Springer 2004; pp. 349-80.
[http://dx.doi.org/10.1007/978-1-4757-4371-5_11]
[17]
Stratta RJ, Gruessner AC, Odorico JS, Fridell JA, Gruessner RW. Pancreas transplantation: An alarming crisis in confidence. Am J Transplant 2016; 16(9): 2556-62.
[http://dx.doi.org/10.1111/ajt.13890] [PMID: 27232750]
[18]
Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2016 annual data report: pancreas. Am J Transplant 2018; 18(Suppl. 1): 114-71.
[http://dx.doi.org/10.1111/ajt.14558] [PMID: 29292605]
[19]
Boggi U, Vistoli F, Amorese G, et al. Long-term (5 years) efficacy and safety of pancreas transplantation alone in type 1 diabetic patients. Transplantation 2012; 93(8): 842-6.
[http://dx.doi.org/10.1097/TP.0b013e318247a782] [PMID: 22314339]
[20]
Coppelli A, Giannarelli R, Mariotti R, et al. Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients. Transplantation 2003; 76(6): 974-6.
[http://dx.doi.org/10.1097/01.TP.0000084202.18999.1D] [PMID: 14508364]
[21]
Giannarelli R, Coppelli A, Sartini MS, et al. Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients. Diabetologia 2006; 49(12): 2977-82.
[http://dx.doi.org/10.1007/s00125-006-0463-5] [PMID: 17021920]
[22]
Coppelli A, Giannarelli R, Boggi U, et al. Disappearance of nephrotic syndrome in type 1 diabetic patients following pancreas transplant alone. Transplantation 2006; 81(7): 1067-8.
[http://dx.doi.org/10.1097/01.tp.0000199270.35555.97] [PMID: 16612286]
[23]
Occhipinti M, Rondinini L, Mariotti R, et al. Amelioration of cardiac morphology and function in type 1 diabetic patients with sustained success of pancreas transplant alone. Diabetes Care 2014; 37(8): e171-2.
[http://dx.doi.org/10.2337/dc14-0061] [PMID: 25061145]
[24]
Kim SJ, Smail N, Paraskevas S, Schiff J, Cantarovich M. Kidney function before pancreas transplant alone predicts subsequent risk of end-stage renal disease. Transplantation 2014; 97(6): 675-80.
[PMID: 24637866]
[25]
Odorico JS, Voss B, Munoz Del Rio A, et al. Kidney function after solitary pancreas transplantation. Transplant Proc 2008; 40(2): 513-5.
[http://dx.doi.org/10.1016/j.transproceed.2008.01.038] [PMID: 18374117]
[26]
Tydén G, Tollemar J, Bolinder J. Combined pancreas and kidney transplantation improves survival in patients with end-stage diabetic nephropathy. Clin Transplant 2000; 14(5): 505-8.
[http://dx.doi.org/10.1034/j.1399-0012.2000.140510.x] [PMID: 11048997]
[27]
Ojo AO, Meier-Kriesche HU, Hanson JA, et al. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 2001; 71(1): 82-90.
[http://dx.doi.org/10.1097/00007890-200101150-00014] [PMID: 11211201]
[28]
Fridell JA, Mangus RS, Chen JM, et al. Steroid-free three-drug maintenance regimen for pancreas transplant alone: Comparison of induction with rabbit antithymocyte globulin +/- rituximab. Am J Transplant 2018; 18(12): 3000-6.
[http://dx.doi.org/10.1111/ajt.14921] [PMID: 29738100]
[29]
Mujtaba MA, Sharfuddin AA, Taber T, et al. Conversion from tacrolimus to belatacept to prevent the progression of chronic kidney disease in pancreas transplantation: case report of two patients. Am J Transplant 2014; 14(11): 2657-61.
[http://dx.doi.org/10.1111/ajt.12863] [PMID: 25179306]
[30]
Niederhaus SV, Kaufman DB, Odorico JS. Induction therapy in pancreas transplantation. Transpl Int 2013; 26(7): 704-14.
[http://dx.doi.org/10.1111/tri.12122] [PMID: 23672537]
[31]
Stratta RJ, Farney AC, Rogers J, Orlando G. Immunosuppression for pancreas transplantation with an emphasis on antibody induction strategies: review and perspective. Expert Rev Clin Immunol 2014; 10(1): 117-32.
[http://dx.doi.org/10.1586/1744666X.2014.853616] [PMID: 24236648]
[32]
Brennan DC, Daller JA, Lake KD, Cibrik D, Del Castillo D. Thymoglobulin Induction Study Group. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006; 355(19): 1967-77.
[http://dx.doi.org/10.1056/NEJMoa060068] [PMID: 17093248]
[33]
Hanaway MJ, Woodle ES, Mulgaonkar S, et al. INTAC Study Group. Alemtuzumab induction in renal transplantation. N Engl J Med 2011; 364(20): 1909-19.
[http://dx.doi.org/10.1056/NEJMoa1009546] [PMID: 21591943]
[34]
Thomusch O, Wiesener M, Opgenoorth M, et al. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet 2016; 388(10063): 3006-16.
[http://dx.doi.org/10.1016/S0140-6736(16)32187-0] [PMID: 27871759]
[35]
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(4): 1019-25.
[http://dx.doi.org/10.1111/ajt.12167] [PMID: 23432918]
[36]
Kaufman DB, Burke GW III, Bruce DS, et al. Prospective, randomized, multi-center trial of antibody induction therapy in simultaneous pancreas-kidney transplantation. Am J Transplant 2003; 3(7): 855-64.
[http://dx.doi.org/10.1034/j.1600-6143.2003.00160.x] [PMID: 12814477]
[37]
Issa N, Amer H, Dean PG, et al. Posttransplant lymphoproliferative disorder following pancreas transplantation. Am J Transplant 2009; 9(8): 1894-902.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02691.x] [PMID: 19519812]
[38]
Arbogast H, Malaise J, Illner WD, et al. Acute cellular and antibody-mediated rejection of the pancreas allograft: incidence, risk factors and outcomes. Am J Transplant 2013; 13: 2945-55.
[http://dx.doi.org/10.1093/ndt/gfh1077]
[39]
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(11): 2945-55.
[http://dx.doi.org/10.1111/ajt.12443] [PMID: 24102905]
[40]
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(2): 173-83.
[http://dx.doi.org/10.1111/tri.12687] [PMID: 26404891]
[41]
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(5): E492-9.
[http://dx.doi.org/10.1111/ctr.12005] [PMID: 22938159]
[42]
Mittal S, Page SL, Friend PJ, Sharples EJ, Fuggle SV. De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure. Am J Transplant 2014; 14(7): 1664-71.
[http://dx.doi.org/10.1111/ajt.12750] [PMID: 24866735]
[43]
Feucht HE, Schneeberger H, Hillebrand G, et al. Capillary deposition of C4d complement fragment and early renal graft loss. Kidney Int 1993; 43(6): 1333-8.
[http://dx.doi.org/10.1038/ki.1993.187] [PMID: 8315947]
[44]
Collins AB, Schneeberger EE, Pascual MA, et al. Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol 1999; 10(10): 2208-14.
[PMID: 10505698]
[45]
Kerman RH, Susskind B, Buelow R, et al. Correlation of ELISA-detected IgG and IgA anti-HLA antibodies in pretransplant sera with renal allograft rejection. Transplantation 1996; 62(2): 201-5.
[http://dx.doi.org/10.1097/00007890-199607270-00009] [PMID: 8755816]
[46]
Tait BD, Süsal C, Gebel HM, et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 2013; 95(1): 19-47.
[http://dx.doi.org/10.1097/TP.0b013e31827a19cc] [PMID: 23238534]
[47]
Maglione M, Ploeg RJ, Friend PJ. Donor risk factors, retrieval technique, preservation and ischemia/reperfusion injury in pancreas transplantation. Curr Opin Organ Transplant 2013; 18(1): 83-8.
[http://dx.doi.org/10.1097/MOT.0b013e32835c29ef] [PMID: 23254698]
[48]
Tambur AR, Ramon DS, Kaufman DB, et al. Perception versus reality?: Virtual crossmatch--how to overcome some of the technical and logistic limitations. Am J Transplant 2009; 9(8): 1886-93.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02724.x] [PMID: 19563341]
[49]
Eby BC, Redfield RR, Ellis TM, Leverson GE, Schenian AR, Odorico JS. Virtual HLA crossmatching as a means to safely expedite transplantation of imported pancreata. Transplantation 2016; 100(5): 1103-10.
[http://dx.doi.org/10.1097/TP.0000000000001125] [PMID: 26950720]
[50]
Desai DM, Scandling JD, Knoppel C, Dafoe DC, Alfrey EJ. Low dose OKT3 treatment for rejection/induction in kidney and kidney pancreas transplantation. Transplant Proc 1998; 30(4): 1552-4.
[http://dx.doi.org/10.1016/S0041-1345(98)00354-6] [PMID: 9636630]
[51]
Burke GW, Ciancio G, Alejandro R, et al. Use of tacrolimus and mycophenolate mofetil for pancreas-kidney transplantation with or without OKT3 induction. Transplant Proc 1998; 30(4): 1544-5.
[http://dx.doi.org/10.1016/S0041-1345(98)00350-9] [PMID: 9636627]
[52]
Rosenberg L. Pancreas transplantation with ATG vs OKT3. Transplant Proc 1997; 29(7A): 35S-6S.
[http://dx.doi.org/10.1016/S0041-1345(97)80010-3] [PMID: 9366927]
[53]
Chow FY, Polkinghorne K, Saunder A, Kerr PG, Atkins RC, Chadban SJ. Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation. Nephrology (Carlton) 2003; 8(4): 212-6.
[http://dx.doi.org/10.1046/j.1440-1797.2003.00158.x] [PMID: 15012723]
[54]
Boubenider S, Hiesse C, Goupy C, Kriaa F, Marchand S, Charpentier B. Incidence and consequences of post-transplantation lymphoproliferative disorders. J Nephrol 1997; 10(3): 136-45.
[PMID: 9238621]
[55]
Kamath S, Dean D, Peddi VR, et al. Efficacy of OKT3 as primary therapy for histologically confirmed acute renal allograft rejection. Transplantation 1997; 64(10): 1428-32.
[http://dx.doi.org/10.1097/00007890-199711270-00009] [PMID: 9392306]
[56]
Todd PA, Brogden RN. Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs 1989; 37(6): 871-99.
[http://dx.doi.org/10.2165/00003495-198937060-00004] [PMID: 2503348]
[57]
Redfield RR, Kaufman DB, Odorico JS. Diagnosis and treatment of pancreas rejection. Curr Transplant Rep 2015; 2(2): 169-75.
[http://dx.doi.org/10.1007/s40472-015-0061-x] [PMID: 26000231]
[58]
Thai NL, Khan A, Tom K, et al. Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One and two year outcomes. Transplantation 2006; 82(12): 1621-4.
[http://dx.doi.org/10.1097/01.tp.0000250712.12389.3d] [PMID: 17198247]
[59]
Clatworthy MR, Sivaprakasam R, Butler AJ, Watson CJ. Subcutaneous administration of alemtuzumab in simultaneous pancreas-kidney transplantation. Transplantation 2007; 84(12): 1563-7.
[http://dx.doi.org/10.1097/01.tp.0000295718.55669.3a] [PMID: 18165765]
[60]
Muthusamy AS, Vaidya AC, Sinha S, Roy D, Elker DE, Friend PJ. Alemtuzumab induction and steroid-free maintenance immunosuppression in pancreas transplantation. Am J Transplant 2008; 8(10): 2126-31.
[http://dx.doi.org/10.1111/j.1600-6143.2008.02373.x] [PMID: 18828772]
[61]
Uemura T, Ramprasad V, Matsushima K, et al. Single dose of alemtuzumab induction with steroid-free maintenance immunosuppression in pancreas transplantation. Transplantation 2011; 92(6): 678-85.
[http://dx.doi.org/10.1097/TP.0b013e31822b58be] [PMID: 21841541]
[62]
Boggi U, Danesi R, Vistoli F, et al. A benefit-risk assessment of basiliximab in renal transplantation. Drug Saf 2004; 27(2): 91-106.
[http://dx.doi.org/10.2165/00002018-200427020-00002] [PMID: 14717621]
[63]
Boggi U, Vistoli F, Coppelli A, Marchetti P, Rizzo G, Mosca F. Use of basiliximab in conjunction with either Neora/MMF/steroids or Prograf/MMF/steroids in simultaneous pancreas-kidney transplantation. Transplant Proc 2001; 33(7-8): 3201-2.
[http://dx.doi.org/10.1016/S0041-1345(01)02362-4] [PMID: 11750373]
[64]
Stratta RJ, Alloway RR, Lo A, Hodge E. Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: primary endpoint analysis of a multicenter, randomized study. Transplantation 2003; 75(8): 1260-6.
[http://dx.doi.org/10.1097/01.TP.0000062838.38351.2A] [PMID: 12717213]
[65]
Stratta RJ, Alloway RR, Lo A, Hodge EE. A prospective, randomized, multicenter study evaluating the safety and efficacy of two dosing regimens of daclizumab compared to no antibody induction in simultaneous kidney-pancreas transplantation: results at 3 years. Transplant Proc 2005; 37(8): 3531-4.
[http://dx.doi.org/10.1016/j.transproceed.2005.09.058] [PMID: 16298651]
[66]
Burke GW III, Kaufman DB, Millis JM, et al. Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results. Transplantation 2004; 77(8): 1269-75.
[http://dx.doi.org/10.1097/01.TP.0000123903.12311.36] [PMID: 15114097]
[67]
Boggi U, Mosca F, Vistoli F, et al. Ninety-five percent insulin independence rate 3 years after pancreas transplantation alone with portal-enteric drainage. Transplant Proc 2005; 37(2): 1274-7.
[http://dx.doi.org/10.1016/j.transproceed.2005.01.024] [PMID: 15848693]
[68]
Becker LE, Nogueira VA, Abensur H, et al. No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas transplantation: a comparative analysis. Transplant Proc 2006; 38(6): 1933-6.
[http://dx.doi.org/10.1016/j.transproceed.2006.06.072] [PMID: 16908327]
[69]
Zhang R, Florman S, Devidoss S, et al. The long-term survival of simultaneous pancreas and kidney transplant with basiliximab induction therapy. Clin Transplant 2007; 21(5): 583-9.
[http://dx.doi.org/10.1111/j.1399-0012.2007.00692.x] [PMID: 17845631]
[70]
Bazerbachi F, Selzner M, Boehnert MU, et al. Thymoglobulin versus basiliximab induction therapy for simultaneous kidney-pancreas transplantation: impact on rejection, graft function, and long-term outcome. Transplantation 2011; 92(9): 1039-43.
[http://dx.doi.org/10.1097/TP.0b013e3182313e4f] [PMID: 22002345]
[71]
Fernández-Burgos I, Montiel Casado MC, Pérez-Daga JA, et al. Induction therapy in simultaneous pancreas-kidney transplantation: thymoglobulin versus basiliximab. Transplant Proc 2015; 47(1): 120-2.
[http://dx.doi.org/10.1016/j.transproceed.2014.12.003] [PMID: 25645787]
[72]
Kaufman DB, Leventhal JR, Koffron AJ, et al. A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus. Transplantation 2002; 73(2): 169-77.
[http://dx.doi.org/10.1097/00007890-200201270-00004] [PMID: 11821726]
[73]
Rajab A, Pelletier RP, Ferguson RM, Elkhammas EA, Bumgardner GL, Henry ML. Steroid-free maintenance immunosuppression with rapamune and low-dose neoral in pancreas transplant recipients. Transplantation 2007; 84(9): 1131-7.
[http://dx.doi.org/10.1097/01.tp.0000287117.98785.54] [PMID: 17998868]
[74]
Axelrod D, Leventhal JR, Gallon LG, Parker MA, Kaufman DB. Reduction of CMV disease with steroid-free immunosuppresssion in simultaneous pancreas-kidney transplant recipients. Am J Transplant 2005; 5(6): 1423-9.
[http://dx.doi.org/10.1111/j.1600-6143.2005.00855.x] [PMID: 15888050]
[75]
Reddy KS, Devarapalli Y, Mazur M, et al. Alemtuzumab with rapid steroid taper in simultaneous kidney and pancreas transplantation: comparison to induction with antithymocyte globulin. Transplant Proc 2010; 42(6): 2006-8.
[http://dx.doi.org/10.1016/j.transproceed.2010.05.090] [PMID: 20692393]
[76]
Kaufman DB, Leventhal JR, Gallon LG, Parker MA. Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results. Am J Transplant 2006; 6(2): 331-9.
[http://dx.doi.org/10.1111/j.1600-6143.2005.01166.x] [PMID: 16426317]
[77]
Gruessner RW, Kandaswamy R, Humar A, Gruessner AC, Sutherland DE. Calcineurin inhibitor- and steroid-free immunosuppression in pancreas-kidney and solitary pancreas transplantation. Transplantation 2005; 79(9): 1184-9.
[http://dx.doi.org/10.1097/01.TP.0000161221.17627.8A] [PMID: 15880067]
[78]
Farney AC, Doares W, Rogers J, et al. A randomized trial of alemtuzumab versus antithymocyte globulin induction in renal and pancreas transplantation. Transplantation 2009; 88(6): 810-9.
[http://dx.doi.org/10.1097/TP.0b013e3181b4acfb] [PMID: 19920781]
[79]
Bösmüller C, Ollinger R, Sieb M, et al. Tacrolimus monotherapy following alemtuzumab induction in combined kidney-pancreas transplantation: results of a prospective randomized trial. Ann Transplant 2012; 17(4): 45-51.
[http://dx.doi.org/10.12659/AOT.883693] [PMID: 23274323]
[80]
Bank JR, Heidt S, Moes DJ, et al. Alemtuzumab induction and delayed acute rejection in steroid-free simultaneous pancreas-kidney transplant recipients. Transplant Direct 2016; 3(1) e124
[http://dx.doi.org/10.1097/TXD.0000000000000634] [PMID: 28349124]
[81]
Magliocca JF, Odorico JS, Pirsch JD, et al. A comparison of alemtuzumab with basiliximab induction in simultaneous pancreas-kidney transplantation. Am J Transplant 2008; 8(8): 1702-10.
[http://dx.doi.org/10.1111/j.1600-6143.2008.02299.x] [PMID: 18694474]
[82]
Bechstein WO, Malaise J, Saudek F, et al. EuroSPK Study Group. Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial. Transplantation 2004; 77(8): 1221-8.
[http://dx.doi.org/10.1097/01.TP.0000120865.96360.DF] [PMID: 15114089]
[83]
Saudek F, Malaise J, Boucek P, Adamec M. Euro-SPK Study Group. Efficacy and safety of tacrolimus compared with cyclosporin microemulsion in primary SPK transplantation: 3-year results of the Euro-SPK 001 trial. Nephrol Dial Transplant 2005; 20(Suppl. 2): ii3-10.
[http://dx.doi.org/10.1093/ndt/gfh1076] [PMID: 15814547]
[84]
Boggi U, Vistoli F, Del Chiaro M, et al. Neoral versus prograf in simultaneous pancreas-kidney transplantation with portal venous drainage: three-year results of a single-center, open-label, prospective, randomized pilot study. Transplant Proc 2005; 37(6): 2641-3.
[http://dx.doi.org/10.1016/j.transproceed.2005.06.086] [PMID: 16182772]
[85]
Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343(4): 230-8.
[http://dx.doi.org/10.1056/NEJM200007273430401] [PMID: 10911004]
[86]
Barlow AD, Nicholson ML, Herbert TP. Evidence for rapamycin toxicity in pancreatic β-cells and a review of the underlying molecular mechanisms. Diabetes 2013; 62(8): 2674-82.
[http://dx.doi.org/10.2337/db13-0106] [PMID: 23881200]
[87]
Fernandes-Silva G, Ivani de Paula M, Rangel ÉB. mTOR inhibitors in pancreas transplant: adverse effects and drug-drug interactions. Expert Opin Drug Metab Toxicol 2017; 13(4): 367-85.
[http://dx.doi.org/10.1080/17425255.2017.1239708] [PMID: 27659512]
[88]
Zaza G, Granata S, Tomei P, Masola V, Gambaro G, Lupo A. mTOR inhibitors and renal allograft: Yin and Yang. J Nephrol 2014; 27(5): 495-506.
[http://dx.doi.org/10.1007/s40620-014-0103-y] [PMID: 24804854]
[89]
Zaza G, Tomei P, Ria P, Granata S, Boschiero L, Lupo A. Systemic and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors. Clin Dev Immunol 2013; 2013, 403280
[http://dx.doi.org/10.1155/2013/403280] [PMID: 24151517]
[90]
Murakami N, Riella LV, Funakoshi T. Risk of metabolic complications in kidney transplantation after conversion to mTOR inhibitor: a systematic review and meta-analysis. Am J Transplant 2014; 14(10): 2317-27.
[http://dx.doi.org/10.1111/ajt.12852] [PMID: 25146383]
[91]
Pengel LH, Liu LQ, Morris PJ. Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials. Transpl Int 2011; 24(12): 1216-30.
[http://dx.doi.org/10.1111/j.1432-2277.2011.01357.x] [PMID: 21955006]
[92]
Badve SV, Pascoe EM, Burke M, et al. Mammalian target of rapamycin inhibitors and clinical outcomes in adult kidney transplant recipients. Clin J Am Soc Nephrol 2016; 11(10): 1845-55.
[http://dx.doi.org/10.2215/CJN.00190116] [PMID: 27445164]
[93]
Knight RJ, Graviss EA, Nguyen DT, et al. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia. Clin Transplant 2018; 32(6) e13265
[http://dx.doi.org/10.1111/ctr.13265] [PMID: 29676018]
[94]
Gupta A, Kaplan B. Transplantation: CNIs to mTOR inhibitors--effects on allosensitization? Nat Rev Nephrol 2014; 10(8): 425-6.
[http://dx.doi.org/10.1038/nrneph.2014.94] [PMID: 24861082]
[95]
Knight RJ, Podder H, Kerman RH, et al. Comparing an early corticosteroid/late calcineurin-free immunosuppression protocol to a sirolimus-, cyclosporine A-, and prednisone-based regimen for pancreas-kidney transplantation. Transplantation 2010; 89(6): 727-32.
[http://dx.doi.org/10.1097/TP.0b013e3181c9dc9b] [PMID: 20195219]
[96]
Ciancio G, Sageshima J, Chen L, et al. Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years. Am J Transplant 2012; 12(12): 3363-76.
[http://dx.doi.org/10.1111/j.1600-6143.2012.04235.x] [PMID: 22946986]
[97]
Kandula P, Fridell J, Taber TE, et al. Impact of tacrolimus-sirolimus maintenance immunosuppression on proteinuria and kidney function in pancreas transplant alone recipients. Transplantation 2012; 94(9): 940-6.
[http://dx.doi.org/10.1097/TP.0b013e3182696a13] [PMID: 23037007]
[98]
Sageshima J, Ciancio G, Chen L, et al. Everolimus with low-dose tacrolimus in simultaneous pancreas and kidney transplantation. Clin Transplant 2014; 28(7): 797-801.
[http://dx.doi.org/10.1111/ctr.12381] [PMID: 24779669]
[99]
Porubsky M, Gruessner AC, Rana A, Jie T, Gruessner RW. Excellent outcomes can be achieved in young pancreas transplant alone recipients by addition of sirolimus to maintenance immunosuppression regimen. Transplant Proc 2014; 46(6): 1932-5.
[http://dx.doi.org/10.1016/j.transproceed.2014.06.010] [PMID: 25131074]
[100]
Li J, Koch M, Kramer K, et al. Dual antibody induction and de novo use of everolimus enable low-dose tacrolimus with early corticosteroid withdrawal in simultaneous pancreas-kidney transplantation. Transpl Immunol 2018; 50: 26-33.
[http://dx.doi.org/10.1016/j.trim.2018.06.001] [PMID: 29885442]
[101]
Stegall MD, Simon M, Wachs ME, Chan L, Nolan C, Kam I. Mycophenolate mofetil decreases rejection in simultaneous pancreas-kidney transplantation when combined with tacrolimus or cyclosporine. Transplantation 1997; 64(12): 1695-700.
[http://dx.doi.org/10.1097/00007890-199712270-00011] [PMID: 9422404]
[102]
Odorico JS, Pirsch JD, Knechtle SJ, D’Alessandro AM, Sollinger HW. A study comparing mycophenolate mofetil to azathioprine in simultaneous pancreas-kidney transplantation. Transplantation 1998; 66(12): 1751-9.
[http://dx.doi.org/10.1097/00007890-199812270-00032] [PMID: 9884272]
[103]
Merion RM, Henry ML, Melzer JS, Sollinger HW, Sutherland DE, Taylor RJ. Randomized, prospective trial of mycophenolate mofetil versus azathioprine for prevention of acute renal allograft rejection after simultaneous kidney-pancreas transplantation. Transplantation 2000; 70(1): 105-11.
[PMID: 10919583]
[104]
Oh JM, Wiland AM, Klassen DK, Weidle PJ, Bartlett ST. Comparison of azathioprine and mycophenolate mofetil for the prevention of acute rejection in recipients of pancreas transplantation. J Clin Pharmacol 2001; 41(8): 861-9.
[http://dx.doi.org/10.1177/00912700122010762] [PMID: 11504274]
[105]
Freise CE, Kang SM, Feng S, Hirose R, Stock P. Excellent short-term results with steroid-free maintenance immunosuppression in low-risk simultaneous pancreas-kidney transplantation. Arch Surg 2003; 138(10): 1121-5.
[http://dx.doi.org/10.1001/archsurg.138.10.1121] [PMID: 14557130]
[106]
Cantarovich D, Karam G, Hourmant M, et al. Steroid avoidance versus steroid withdrawal after simultaneous pancreas-kidney transplantation. Am J Transplant 2005; 5(6): 1332-8.
[http://dx.doi.org/10.1111/j.1600-6143.2005.00816.x] [PMID: 15888038]
[107]
Aoun M, Eschewege P, Hamoudi Y, et al. Very early steroid withdrawal in simultaneous pancreas-kidney transplants. Nephrol Dial Transplant 2007; 22(3): 899-905.
[http://dx.doi.org/10.1093/ndt/gfl660] [PMID: 17127698]
[108]
Gallon LG, Winoto J, Chhabra D, Parker MA, Leventhal JR, Kaufman DB. Long-term renal transplant function in recipient of simultaneous kidney and pancreas transplant maintained with two prednisone-free maintenance immunosuppressive combinations: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus. Transplantation 2007; 83(10): 1324-9.
[http://dx.doi.org/10.1097/01.tp.0000264189.58324.91] [PMID: 17519781]
[109]
Malvezzi P, Rostaing L. The safety of calcineurin inhibitors for kidney-transplant patients. Expert Opin Drug Saf 2015; 14(10): 1531-46.
[http://dx.doi.org/10.1517/14740338.2015.1083974] [PMID: 26329325]
[110]
Grimbert P, Thaunat O. mTOR inhibitors and risk of chronic antibody-mediated rejection after kidney transplantation: where are we now? Transpl Int 2017; 30(7): 647-57.
[http://dx.doi.org/10.1111/tri.12975] [PMID: 28445619]
[111]
Weir MR, Diekmann F, Flechner SM, et al. mTOR inhibition: the learning curve in kidney transplantation. Transpl Int 2010; 23(5): 447-60.
[http://dx.doi.org/10.1111/j.1432-2277.2010.01051.x] [PMID: 20136784]

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