Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant options for patients with diabetes requiring insulin therapy and chronic kidney disease who are suitable candidates for kidney transplantation should include consideration of β-cell replacement therapy: pancreas or islet transplantation. International variation related to national regulatory policies exists in offering one or both options to suitable candidates and is further affected by pancreas/islet allocation policies and transplant waiting list dynamics. The selection of appropriate candidates depends on patient age, coexistent morbidities, the timing of referral to the transplant center (predialysis versus on dialysis) and availability of living kidney donors. Therefore, early referral (estimated glomerular filtration rate < 30 mL/min/1.73 m2) is of the utmost importance to ensure adequate time for informed decision making and thorough pretransplant evaluation. Obesity, cardiovascular disease, peripheral vascular disease, smoking, and frailty are some of the conditions that need to be addressed before acceptance on the transplant list, and ideally before dialysis becoming imminent. This review offers insights into selection of pancreas/islet transplant candidates by transplant centers and an update on posttransplant outcomes, which may have practice implications for referring nephrologists.

CHU Lille Department of Endocrinology Diabetology and Metabolism Inserm U1190 Translational Research for Diabetes Univ Lille European Genomic Institute for Diabetes Lille France

Department of Medicine Leiden University Medical Center Leiden the Netherlands

Department of Nephrology St Vincent's Hospital Melbourne Australia

Diabetes Center Institute for Clinical and Experimental Medicine Prague Czech Republic

Division of Diabetes Endocrinology and Gastroenterology Faculty of Biology Medicine and Health Manchester Academic Health Centre University of Manchester Manchester United Kingdom

Division of Endocrinology Diabetes and Metabolism Department of Medicine University of Pennsylvania Perelman School of Medicine Philadelphia PA

Division of Nephrology and Hypertension Mayo Clinic Rochester MN

Division of Nephrology Department of Medicine Beth Isreal Deaconess Medical Center Boston MA

Division of Nephrology Department of Medicine University of Wisconsin Madison WI

Division of Nephrology Hospital Clinic of Barcelona Barcelona Spain

Division of Transplantation Department of Surgery Asan Medical Center Seoul South Korea

Medstar Georgetown Transplant Institute Washington DC

Nuffield Department of Surgical Sciences University of Oxford Oxford United Kingdom

Zobrazit více v PubMed

Larsen JL. Pancreas transplantation: Indications and consequences. Endocrine Reviews.2004;25(6): 919–946. PubMed

Rickels MR, Robertson RP. Pancreatic Islet Transplantation in Humans: Recent Progress and Future Directions. Endocr Rev. 2019;40(2): 631–668. PubMed PMC

Choudhary P RM, Senior PA, Vantyghem MC, Maffi P, Kay TW, Keymeulen B, Inagaki N, Saudek F, Lehmann R, Hering BJ. Evidence-Informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia. Diabetes Care. 2015;38(6): 1016–1029. PubMed PMC

Fridell JA, Powelson JA. Pancreas after kidney transplantation: why is the most logical option the least popular? Curr Opin Organ Transplant. 2015;20(1): 108–114. PubMed

Stratta RJ, Fridell JA, Gruessner AC, Odorico JS, Gruessner RW. Pancreas transplantation: a decade of decline. Curr Opin Organ Transplant. 2016;21(4): 386–392. PubMed

Benjamens S, Leemkuil M, Margreiter C, Huurman VA, Leuvenink HG, Pol RA. A steady decline in pancreas transplantation rates. Pancreatology. 2019;19(1): 31–38. PubMed

Matsumoto I, Sawada T, Nakano M, et al. Improvement in islet yield from obese donors for human islet transplants. Transplantation. 2004;78(6): 880–885. PubMed

Rickels MR, Stock PG, de Koning EJP, et al. Defining Outcomes for beta-cell Replacement Therapy in the Treatment of Diabetes: A Consensus Report on the Igls Criteria From the IPITA/EPITA Opinion Leaders Workshop. Transplantation. 2018;102(9): 1479–1486. PubMed PMC

Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2016 Annual Data Report: Pancreas. Am J Transplant. 2018;18 Suppl 1: 114–171. PubMed

Goodman J, Becker YT. Pancreas surgical complications. Curr Opin Organ Transplant. 2009;14(1): 85–89. PubMed

Shapiro AM, Pokrywczynska M, Ricordi C. Clinical pancreatic islet transplantation. Nat Rev Endocrinol. 2017;13(5): 268–277. PubMed

(CITR) CITR. Collaborative Islet Transplant Registry - Ninth Annual Report 2016. https://citregistry.org/content/citr-9th-annual-report.

Koh A, Senior P, Salam A, et al. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation. 2010;89(4): 465–471. PubMed

Al-Adra DP, Gill RS, Imes S, et al. Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus. Transplantation. 2014;98(9): 1007–1012. PubMed

Hering BJ, Kandaswamy R, Ansite JD, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. Jama-Journal of the American Medical Association. 2005;293(7): 830–835. PubMed

Rickels MR, Liu C, Shlansky-Goldberg RD, et al. Improvement in beta-cell secretory capacity after human islet transplantation according to the CIT07 protocol. Diabetes. 2013;62(8): 2890–2897. PubMed PMC

Markmann JF, Rickels MR, Eggerman TL, et al. Phase 3 Trial of Human Islet-after-Kidney Transplantation in Type 1 Diabetes. Am J Transplant. 2020. PubMed PMC

Pelletier RP, Rajab AA, Diez A, et al. Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation. Clin Transplant.2015;29(12): 1119–1127. PubMed

Lehmann R, Graziano J, Brockmann J, et al. Glycemic Control in Simultaneous Islet-Kidney Versus Pancreas-Kidney Transplantation in Type 1 Diabetes: A Prospective 13-Year Follow-up. Diabetes Care. 2015;38(5): 752–759. PubMed

Flatt AJS, Bennett D, Counter C, Brown AL, White SA, Shaw JAM. beta-Cell and renal transplantation options for diabetes. Diabet Med. 2020;37(4): 580–592. PubMed

Scalea JR, Redfield RR 3rd, Arpali E, et al. Pancreas transplantation in older patients is safe, but patient selection is paramount. Transpl Int. 2016;29(7): 810–818. PubMed

Montagud-Marrahi E, Molina-Andújar A, Pané A, et al. Outcomes of pancreas transplantation in older diabetic patients. BMJ Open Diabetes Res Care. 2020;8(1). PubMed PMC

(WHO) WHO. Classification of Diabetes Mellitus 2019. https://apps.who.int/iris/rest/bitstreams/1233344/retrieve.

Katz LE, Jawad AF, Ganesh J, Abraham M, Murphy K, Lipman TH. Fasting c-peptide and insulin-like growth factor-binding protein-1 levels help to distinguish childhood type 1 and type 2 diabetes at diagnosis. Pediatr Diabetes. 2007;8(2): 53–59. PubMed

Weems P, Cooper M. Pancreas transplantation in type II diabetes mellitus. World J Transplant. 2014;4(4): 216–221. PubMed PMC

Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2018 Annual Data Report: Pancreas. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020;20 Suppl s1: 131–192. PubMed

Gruessner AC, Gruessner RWG. Pancreas Transplantation for Patients with Type 1 and Type 2 Diabetes Mellitus in the United States: A Registry Report. Gastroenterol Clin North Am. 2018;47(2): 417–441. PubMed

Al-Qaoud TM, Odorico JS, Redfield RR 3rd. Pancreas transplantation in type 2 diabetes: expanding the criteria. Curr Opin Organ Transplant. 2018;23(4): 454–460. PubMed

Rohan V, Taber D, Palanisamy A, et al. Impact of Type 1 and Type 2 Diabetes Mellitus on Pancreas Transplant Outcomes. Exp Clin Transplant. 2019;17(6): 796–802. PubMed

Andacoglu OM, Himmler A, Geng X, et al. Comparison of glycemic control after pancreas transplantation for Type 1 and Type 2 diabetic recipients at a high volume center. Clin Transplant. 2019;33(8): e13656. PubMed

Sasaki TM, Gray RS, Ratner RE, et al. Successful long-term kidney-pancreas transplants in diabetic patients with high C-peptide levels. Transplantation. 1998;65(11): 1510–1512. PubMed

Smail N, Paraskevas S, Tan X, Metrakos P, Cantarovich M. Renal function in recipients of pancreas transplant alone. Current opinion in organ transplantation. 2012;17(1): 73–79. PubMed

Odorico JS, Voss B, Munoz Del Rio A, et al. Kidney function after solitary pancreas transplantation. Transplant Proc. 2008;40(2): 513–515. PubMed

Rickels MR. Hypoglycemia-associated autonomic failure, counterregulatory responses, and therapeutic options in type 1 diabetes. Ann N Y Acad Sci. 2019;1454(1): 68–79. PubMed PMC

Sureshkumar KK, Patel BM, Markatos A, Nghiem DD, Marcus RJ. Quality of life after organ transplantation in type 1 diabetics with end-stage renal disease. Clin Transplant. 2006;20(1): 19–25. PubMed

Gross CR, Limwattananon C, Matthees B, Zehrer JL, Savik K. Impact of transplantation on quality of life in patients with diabetes and renal dysfunction. Transplantation. 2000;70(12): 1736–1746. PubMed

Sutherland DE, Gruessner RW, Dunn DL, et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001;233(4): 463–501. PubMed PMC

Scheuermann U, Rademacher S, Jahn N, et al. Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation. Health Qual Life Outcomes. 2020;18(1): 303. PubMed PMC

Rajkumar T, Mazid S, Vucak-Dzumhur M, Sykes TM, Elder GJ. Health-related quality of life following kidney and simultaneous pancreas kidney transplantation. Nephrology (Carlton). 2019;24(9): 975–982. PubMed

Gibbons A, Cinnirella M, Bayfield J, et al. Changes in quality of life, health status and other patient-reported outcomes following simultaneous pancreas and kidney transplantation (SPKT): a quantitative and qualitative analysis within a UK-wide programme. Transpl Int. 2020;33(10): 1230–1243. PubMed

Nijhoff MF, Hovens J, Huisman SD, et al. Psychological Symptoms and Quality of Life After Simultaneous Kidney and Pancreas Transplantation. Transplant Direct. 2020;6(5): e552. PubMed PMC

Foster ED, Bridges ND, Feurer ID, et al. Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2018;41(5): 1001–1008. PubMed PMC

Corbin KD, Driscoll KA, Pratley RE, et al. Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms. Endocr Rev. 2018;39(5): 629–663. PubMed

Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med. 2019;381(25): 2440–2450. PubMed

Bedat B, Niclauss N, Jannot AS, et al. Impact of recipient body mass index on short-term and long-term survival of pancreatic grafts. Transplantation. 2015;99(1): 94–99. PubMed

Diwan TS, Lee TC, Nagai S, et al. Obesity, transplantation, and bariatric surgery: An evolving solution for a growing epidemic. Am J Transplant. 2020. PubMed

Dziodzio T, Biebl M, Ollinger R, Pratschke J, Denecke C. The Role of Bariatric Surgery in Abdominal Organ Transplantation-the Next Big Challenge? Obes Surg. 2017;27(10): 2696–2706. PubMed

Aminian A. Bariatric procedure selection in patients with type 2 diabetes: choice between Roux-en-Y gastric bypass or sleeve gastrectomy. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2019. PubMed

Mann DM, Fernandez S, Mondal Z, et al. Role of Coronary Angiography in the Assessment of Cardiovascular Risk in Kidney Transplant Candidates. The American journal of cardiology. 2016;118(5): 679–683. PubMed

Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcified tissue international. 2013;93(4): 365–373. PubMed PMC

Lewis JR, Wong G, Taverniti A, Vucak-Dzumhur M, Elder GJ. Association between Aortic Calcification, Cardiovascular Events, and Mortality in Kidney and Pancreas-Kidney Transplant Recipients. American journal of nephrology. 2019;50(3): 177–186. PubMed

McAdams-DeMarco MA, Van Pilsum Rasmussen SE, Chu NM, et al. Perceptions and Practices Regarding Frailty in Kidney Transplantation: Results of a National Survey. Transplantation. 2020;104(2): 349–356. PubMed PMC

Parajuli S, Swanson KJ, Patel R, et al. Outcomes of simultaneous pancreas and kidney transplants based on preemptive transplant compared to those who were on dialysis before transplant - a retrospective study. Transpl Int. 2020;33(9): 1106–1115. PubMed

Kaku K, Kitada H, Noguchi H, et al. Living Donor Kidney Transplantation Preceding Pancreas Transplantation Reduces Mortality in Type 1 Diabetics With End-stage Renal Disease. Transplantation Proceedings. 2015;47(3): 733–737. PubMed

Sollinger HW, Odorico JS, Becker YT, D’Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Annals of surgery. 2009;250(4): 618–630. PubMed

Gruessner RWG, Sutherland DER, Gruessner AC. Mortality Assessment for Pancreas Transplants. American Journal of Transplantation. 2004;4(12): 2018–2026. PubMed

Vivek B Kute NP, Pankaj R Shah, Pranjal R Modi. Kidney exchange transplantation current status, an update and future perspectives World J Transplant. 2018;June 28(8(3)): 52–60. PubMed PMC

Ruiz S, Amor AJ, Pane A, et al. Cardiovascular risk factors and cardiovascular disease in patients with type 1 diabetes and end-stage renal disease candidates for kidney-pancreas transplantation: Trends from 1999 to 2017. Diabetes Research and Clinical Practice. 2020;163: 108135. PubMed

Sung RS, Zhang M, Schaubel DE, Shu X, Magee JC. A Reassessment of the Survival Advantage of Simultaneous Kidney-Pancreas Versus Kidney-Alone Transplantation. Transplantation. 2015;99(9): 1900–1906. PubMed PMC

Barlow AD, Saeb-Parsy K, Watson CJE. An analysis of the survival outcomes of simultaneous pancreas and kidney transplantation compared to live donor kidney transplantation in patients with type 1 diabetes: a UK Transplant Registry study. Transplant international : official journal of the European Society for Organ Transplantation. 2017;30(9): 884–892. PubMed

Fridell JA, Niederhaus S, Curry M, Urban R, Fox A, Odorico J. The survival advantage of pancreas after kidney transplant. American journal of transplantation. 2019;19(3): 823–830. PubMed

Lindahl JP, Hartmann A, Aakhus S, et al. Long-term cardiovascular outcomes in type 1 diabetic patients after simultaneous pancreas and kidney transplantation compared with living donor kidney transplantation. Diabetologia. 2016;59(4): 844–852. PubMed

Ventura-Aguiar P, Ferrer J, Revuelta I, et al. Pancreas outcomes between living and deceased kidney donor in pancreas after kidney transplantation patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018;33(11): 2052–2059. PubMed

Niederhaus SV, Leverson GE, Lorentzen DF, et al. Acute cellular and antibody-mediated rejection of the pancreas allograft: incidence, risk factors and outcomes. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013;13(11): 2945–2955. PubMed

Dong M, Parsaik AK, Kremers W, et al. Acute pancreas allograft rejection is associated with increased risk of graft failure in pancreas transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013;13(4): 1019–1025. PubMed

Esmeijer K, Hoogeveen EK, van den Boog PJM, et al. Superior Long-Term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort. Diabetes Care. 2019. PubMed

Gruessner AC, Gruessner RWG. 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). The Review of Diabetic Studies. 2016;13(1): 35–58. PubMed PMC

Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2015 Annual Data Report: Pancreas. American Journal of Transplantation. 2017;17: 117–173. PubMed

Kopp WH, Verhagen MJ, Blok JJ, et al. Thirty Years of Pancreas Transplantation at Leiden University Medical Center: Long-term Follow-up in a Large Eurotransplant Center. Transplantation. 2015;99(9): e145–151. PubMed

Finger EB, Radosevich DM, Dunn TB, et al. A composite risk model for predicting technical failure in pancreas transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013;13(7): 1840–1849. PubMed PMC

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. PubMed

Ventura-Aguiar P, Ferrer J, Paredes D, et al. Outcomes From Brain Death Donors With Previous Cardiac Arrest Accepted for Pancreas Transplantation. Annals of Surgery. 2019: 1-1. PubMed

Parajuli S, Bath NM, Aziz F, et al. More than 25 years of pancreas graft survival after simultaneous pancreas and kidney transplantation. Transplantation. 2019: 1-1. PubMed PMC

Lindahl JP, Reinholt FP, Eide IA, et al. In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves long-term kidney graft ultrastructure and function better than transplantation of kidney alone. Diabetologia. 2014;57(11): 2357–2365. PubMed

Helantera I, Ortiz F, Raisanen-Sokolowski A, Koskinen P. Impact of glucose metabolism abnormalities on histopathological changes in kidney transplant protocol biopsies. Transplant international : official journal of the European Society for Organ Transplantation. 2010;23(4): 374–381. PubMed

Coemans M, Van Loon E, Lerut E, et al. Occurrence of Diabetic Nephropathy After Renal Transplantation Despite Intensive Glycemic Control: An Observational Cohort Study. Diabetes Care. 2019;42(4): 625–634. PubMed

Farney AC, Cho E, Schweitzer EJ, et al. Simultaneous cadaver pancreas living-donor kidney transplantation: a new approach for the type 1 diabetic uremic patient. Ann Surg. 2000;232(5): 696–703. PubMed PMC

Choi JY, Jung JH, Shin S, Kim YH, Han DJ. Association between the pancreas transplantation and survival of patients with diabetes: A single center experience. PLoS One. 2017;12(11): e0186827. PubMed PMC

Farney AC, Rogers J, Orlando G, Stratta RJ. Simultaneous transplantation of the living donor kidney and deceased donor pancreas and other transplant options for diabetic and uremic patients. Curr Opin Organ Transplant. 2015;20(1): 103–107. PubMed

Pavlakis M, Khwaja K, Mandelbrot D, et al. Renal allograft failure predictors after PAK transplantation: results from the New England Collaborative Association of Pancreas Programs. Transplantation. 2010;89(11): 1347–1353. PubMed

Parajuli S, Arunachalam A, Swanson KJ, et al. Outcomes after simultaneous kidney-pancreas versus pancreas after kidney transplantation in the current era. Clin Transplant. 2019;33(12): e13732. PubMed

Uva PD, Papadimitriou JC, Drachenberg CB, et al. Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies. Am J Transplant. 2019;19(2): 466–474. PubMed

Vantyghem MC, Chetboun M, Gmyr V, et al. Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes Care. 2019;42(11): 2042–2049. PubMed

Nijhoff MF, Engelse MA, Dubbeld J, et al. Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression. Am J Transplant. 2016;16(1): 246–253. PubMed

Lablanche S, Vantyghem MC, Kessler L, et al. Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2018. PubMed

Lablanche S, Vantyghem MC, Kessler L, et al. Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2018;6(7): 527–537. PubMed

Frank A, Deng S, Huang X, et al. Transplantation for type I diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg. 2004;240(4): 631–640; discussion 640–633. PubMed PMC

Increase in lumbar spine but not distal radius bone mineral density in adults after pancreas kidney transplantation