462
Views
3
CrossRef citations to date
0
Altmetric
Review

pre-existing diabetes and PTDM in kidney transplant recipients: how to handle immunosuppression

, , , & ORCID Icon
Pages 55-66 | Received 10 Aug 2020, Accepted 12 Nov 2020, Published online: 15 Dec 2020

References

  • Saran R, Robinson B, Abbott KC, et al. US Renal Data System 2017 Annual Data Report: epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2018;71(3):A7.
  • Taber DJ, Meadows HB, Pilch NA, et al. Pre-existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation. Clin Transplant. 2013;27(2):274–282.
  • Molnar MZ, Huang E, Hoshino J, et al. Association of pretransplant glycemic control with posttransplant outcomes in diabetic kidney transplant recipients. Diabetes Care. 2011;34(12):2536–2541.
  • Hayer MK, Farrugia D, Begaj I, et al. Infection-related mortality is higher for kidney allograft recipients with pretransplant diabetes mellitus. Diabetologia. 2014;57(3):554–561.
  • Schachtner T, Stein M, Reinke P. Diabetic kidney transplant recipients: impaired infection control and increased alloreactivity. Clin Transplant. 2017;31(7).
  • Kleinsteuber A, Halleck F, Khadzhynov D, et al. Impact of Pre-existing Comorbidities on Long-term Outcomes in Kidney Transplant Recipients. Transplant Proc. 2018;50(10):3232–3241.
  • Johal S, Jackson-Spence F, Gillott H, et al. Pre-existing diabetes is a risk factor for increased rates of cellular rejection after kidney transplantation: an observational cohort study. Diabet Med. 2017;34(8):1067–1073.
  • Rostaing L, Neumayer HH, Reyes-Acevedo R, et al. Belatacept-versus cyclosporine-based immunosuppression in renal transplant recipients with pre-existing diabetes. Clin J Am Soc Nephrol. 2011;6:2696–2704.
  • Bertrand D, Terrec F, Etienne I, et al. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort. J Clin Med. 2020;9(2):336-45.
  • Molitch ME, Adler AI, Flyvbjerg A, et al. Diabetic Kidney Disease– A clinical update from Kidney Disease: improving Global Outcomes (KDIGO). Kidney Int. Internet]. 2015 [cited 2020 Jun 30];87:20–30. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214898/
  • Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes Mellitus: causes, Treatment, and Impact on Outcomes. Endocr Rev. Internet]. 2016 [cited 2020 Jun 30];37:37–61. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740345/
  • Langsford D. Dysglycemia after renal transplantation: definition, pathogenesis, outcomes and implications for management. World J Diabetes. 2015;6(10):1132–1151.
  • Gomes V, Ferreira F, Guerra J, et al. New-onset diabetes after kidney transplantation: incidence and associated factors. World J Diabetes. 2018;9(7):132–137.
  • Wilkinson A, Davidson J, Dotta F, et al. Guidelines for the treatment and management of new-onset diabetes after transplantation. Clin Transplant. 2005;19:291–298.
  • Ussif AM, Åsberg A, Halden TAS, et al. Validation of diagnostic utility of fasting plasma glucose and HbA1c in stable renal transplant recipients one year after transplantation. BMC Nephrol. Internet]. 2019 [cited 2020 Jun 30];20. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327477/.
  • Munshi VN, Saghafian S, Cook CB, et al. Comparison of post-transplantation diabetes mellitus incidence and risk factors between kidney and liver transplantation patients. PLoS One. Internet]. 2020 [cited 2020 Jun 30];15. Available from (1): e0226873. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953760/.
  • Iannino N, Nasri A, Räkel A, et al. Temporal Changes on the Risks and Complications of Posttransplantion Diabetes Mellitus Following Cardiac Transplantation. J Transplant. Internet]. 2018 [cited 2020 Jun 30 2018 Jun 30];. Available from 2018: 1–11. : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250037/.
  • Shimada H, Uchida J, Nishide S, et al. Comparison of Glucose Tolerance between Kidney Transplant Recipients and Healthy Controls. J Clin Med. Internet]. 2019 [cited 2020 Jun 30];8. Available from (7): 920. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678426/.
  • Delgado P, Diaz JM, Silva I, et al. Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study. Clin J Am Soc Nephrol. Internet]. 2008 [cited 2020 Jun 30];3:808–813. Available from (3): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386704/.
  • Ghisdal L, Van Laecke S, Abramowicz MJ, et al. New-Onset Diabetes After Renal Transplantation. Diabetes Care. Internet]. 2012 [cited 2020 Jun 30];35:181–188. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241330/.
  • Tufton N, Ahmad S, Rolfe C, et al. New-onset diabetes after renal transplantation. Diabet Med. 2014;31(11):1284–1292.
  • Dedinská I, Ĺ Ĺ, Miklušica M, et al. Twelve-Month and Five-Year Analyses of Risk Factors for New-Onset Diabetes After Transplantation in a Group of Patients Homogeneous for Immunosuppression. Transplant Proc. 2015;47(6):1831–1839.
  • Palepu S, Prasad GVR. New-onset diabetes mellitus after kidney transplantation: current status and future directions. World J Diabetes. 2015;6:445–455.
  • Tillmann FP, Schmitz M, Rump LC, et al. Impact of low-dose steroids on HbA1c levels and development of pre-diabetes and NODAT in non-diabetic renal transplant recipients on long-term follow-up. Int Urol Nephrol. 2018;50(4):771–777.
  • Quteineh L, Wójtowicz A, Bochud P-Y, et al. Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients. Am J Transplant. 2019;19(1):238–246.
  • de Lucena DD, de Sá JR, Medina-Pestana JO, et al. Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: an Observational Cohort Study. J Diabetes Res. 2020;2020:1938703.
  • Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017;127(1):1–4.
  • Stevens RB, Foster KW, Miles CD, et al. A randomized 2 × 2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Transplantation. 2015;99(1):197–209.
  • Stevens RB, Lane JT, Boerner BP, et al. Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia. Clin Transplant. 2012;26(1):123–132.
  • Ducloux D, Courivaud C, Bamoulid J, et al. Immune phenotype predicts new onset diabetes after kidney transplantation. Hum Immunol. 2019;80(11):937–942.
  • Crepin T, Carron C, Roubiou C, et al. ATG-induced accelerated immune senescence: clinical implications in renal transplant recipients. Am J Transplant. 2015;15(4):1028–1038.
  • Aasebø W, Midtvedt K, Valderhaug TG, et al. Impaired glucose homeostasis in renal transplant recipients receiving basiliximab. Nephrol Dial Transplant. 2010;25(4):1289–1293.
  • Prasad N, Gurjer D, Bhadauria D, et al. Is basiliximab induction, a novel risk factor for new onset diabetes after transplantation for living donor renal allograft recipients? Nephrology (Carlton). 2014;19(4):244–250.
  • Luan FL, Steffick DE, Ojo AO. New-onset diabetes mellitus in kidney transplant recipients discharged on steroid-free immunosuppression. Transplantation. 2011;91(3):334–341.
  • Webster AC, Ruster LP, McGee R, et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev. 2010;(1):CD003897.
  • Gonzalez-Molina M, Gentil MA, Burgos D, et al. Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study. NDT Plus. Internet]. 2010 [cited 2020 Jun 30];3:ii32–ii36. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875041/
  • Willicombe M, Rizzello A, Goodall D, et al. Risk factors and outcomes of delayed graft function in renal transplant recipients receiving a steroid sparing immunosuppression protocol. World J Transplant. Internet]. 2017 [cited 2020 Jun 30];7:34–42. Available from (1): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324026/
  • Rodrigo E, Fernández-Fresnedo G, Valero R, et al. New-onset diabetes after kidney transplantation: risk factors. J Am Soc Nephrol. 2006;17:S291–295.
  • Linssen MML, van Raalte DH, Toonen EJM, et al. Prednisolone-induced beta cell dysfunction is associated with impaired endoplasmic reticulum homeostasis in INS-1E cells. Cell Signal. 2011;23:1708–1715.
  • Hwang JL, Weiss RE. Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment. Internet]. 2014 [cited 2020 Jun 30];30:96–102. Available from Diabetes Metab Res Rev https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112077/ 2: .
  • De Lucena DD, Rangel ÉB. Glucocorticoids use in kidney transplant setting. Expert Opin Drug Metab Toxicol. 2018;14(10):1023–1041.
  • Dharnidharka VR, Schnitzler MA, Chen J, et al. Differential Risks for Adverse Outcomes 3-Years after Kidney Transplantation Based on Initial Immunosuppression Regimen: A National Study. Transpl Int. Internet]. 2016 [cited 2020 Jun 30];29:1226–1236. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114846/.
  • Castedal M, Skoglund C, Axelson C, et al. Steroid-free immunosuppression with low-dose tacrolimus is safe and significantly reduces the incidence of new-onset diabetes mellitus following liver transplantation. Scand J Gastroenterol. 2018;53(6):741–747.
  • Serrano OK, Kandaswamy R, Gillingham K, et al. Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes from the University of Minnesota. Transplantation. Internet]. 2017 [cited 2020 Jun 30];101:2590–2598. Available from;(10): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697902/
  • Fairfield C, Penninga L, Powell J, et al. Glucocorticosteroid‐free versus glucocorticosteroid‐containing immunosuppression for liver transplanted patients. Cochrane Database Syst Rev. Internet]. 2018 [cited 2020 Jun 30 2018 Jun 30];. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494590/
  • Rostaing L, Cantarovich D, Mourad G, et al. Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation. 2005;79(7):807–814.
  • Mourad G, Glyda M, Albano L, et al. Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial. Transplantation. 2017;101(8):1924–1934.
  • Woodle ES, First MR, Pirsch J, et al. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg. 2008;248:564–577.
  • JD P, AK H, MR F, et al. New-Onset Diabetes After Transplantation: results From a Double-Blind Early Corticosteroid Withdrawal Trial. Am J Transplant. 2015;15:1982–1990.
  • Torres A, Hernández D, Moreso F, et al. Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus. Kidney Int Rep. 2018;3:1304–1315.
  • Zsom L, Wagner L, Fülöp T. Minimization vs tailoring: where do we stand with personalized immunosuppression during renal transplantation in 2015? World J Transplant. 2015;5:73–80.
  • Cole EH, Prasad GR, Cardella CJ, et al. A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients. Transplant Res. Internet]. 2013 [cited 2020 Jun 30];2:1.Available from (1): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599918/.
  • Yates CJ, Fourlanos S, Colman PG, et al. Divided dosing reduces prednisolone-induced hyperglycaemia and glycaemic variability: a randomized trial after kidney transplantation. Nephrol Dial Transplant. 2014;29(3):698–705.
  • Midtvedt K, Hjelmesaeth J, Hartmann A, et al. Insulin resistance after renal transplantation: the effect of steroid dose reduction and withdrawal. J Am Soc Nephrol. 2004;15:3233–3239.
  • Höcker B, Weber LT, Feneberg R, et al. Improved growth and cardiovascular risk after late steroid withdrawal: 2-year results of a prospective, randomised trial in paediatric renal transplantation. Nephrol Dial Transplant. 2010;25(2):617–624.
  • Ali AK, Guo J, Ahn H, et al. Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: meta-Analysis of Randomized Controlled Trials. Int J Organ Transplant Med. 2011;2:149–159.
  • Leeaphorn N, Garg N, Khankin EV, et al. Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database. Transpl Int. 2018;31(2):175–186.
  • Di Vico MC, Messina M, Fop F, et al. Recurrent IgA nephropathy after renal transplantation and steroid withdrawal. Clin Transplant. 2018;32(4):e13207.
  • Ekberg H, Tedesco-Silva H, Demirbas A, et al., Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 357(25): 2562–2575. 2007.
  • Schmeding M, Kiessling A, Neuhaus R, et al. Mycophenolate mofetil monotherapy in liver transplantation: 5-year follow-up of a prospective randomized trial. Transplantation. 2011;92(8):923–929.
  • Xiao X, Wang J, Chang X, et al. Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats. Mol Med Rep. 2015;12(3):4043–4050.
  • Seo J-W, Kim YG, Lee SH, et al. Mycophenolate Mofetil Ameliorates Diabetic Nephropathy in db/db Mice. Biomed Res Int. 2015;2015:301627.
  • Ugrasbul F, Moore WV, Tong PY, et al. Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat. Pediatr Diabetes. 2008;9(6):596–601.
  • Gottlieb PA, Quinlan S, Krause-Steinrauf H, et al. Failure to Preserve -Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes. Diabetes Care. 2010;33(4):826–832.
  • Bamgbola O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Internet]. 2016 [cited 2020 Jun 30];7:110–127. Available from Ther Adv Endocrinol Metab https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892400/ 3
  • Montero N, Immunosuppression PJ, Hyperglycemia P-T. Curr Diabetes Rev. 2015;11(3):144–154.
  • Bansal SB, Saxena V, Pokhariyal S, et al. Comparison of azathioprine with mycophenolate mofetil in a living donor kidney transplant programme. Indian J Nephrol. 2011;21:258–263.
  • Silverstein J, Maclaren N, Riley W, et al. Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. N Engl J Med. 1988;319(10):599–604.
  • Kasiske BL, Snyder JJ, Gilbertson D, et al. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178–185.
  • Iida S, Ishida H, Tokumoto T, et al. New-onset diabetes after transplantation in tacrolimus-treated, living kidney transplantation: long-term impact and utility of the pre-transplant OGTT. Int Urol Nephrol. Internet]. 2010 [cited 2020 Jun 30];42:935–945. Available from (4): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995209/
  • Yu H, Kim H, Baek CH, et al. Risk factors for new-onset diabetes mellitus after living donor kidney transplantation in Korea - a retrospective single center study. BMC Nephrol. Internet]. 2016 [cited 2020 Jun 30];17. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966790/
  • Shimizu M, Iino Y, Terashi A. [Improvement of insulin sensitivity after renal transplantation measured by a glucose clamp technique]. Nihon Ika Daigaku Zasshi. 1998;65:50–54.
  • Nagaraja P, Ravindran V, Morris-Stiff G, et al. Role of insulin resistance indices in predicting new-onset diabetes after kidney transplantation. Transpl Int. 2013;26(3):273–280.
  • Chakkera HA, Kudva Y, Calcineurin Inhibitors: KB. Pharmacologic Mechanisms Impacting Both Insulin Resistance and Insulin Secretion Leading to Glucose Dysregulation and Diabetes Mellitus. Clin Pharmacol Ther. 2017;101:114–120.
  • Polastri L, Galbiati F, Bertuzzi F, et al. Secretory defects induced by immunosuppressive agents on human pancreatic beta-cells. Acta Diabetol. 2002;39:229–233.
  • Asberg A, Midtvedt K, Voytovich MH, et al. Calcineurin inhibitor effects on glucose metabolism and endothelial function following renal transplantation. Clin Transplant. 2009;23(4):511–518.
  • Li Z, Sun F, Zhang Y, et al. Tacrolimus Induces Insulin Resistance and Increases the Glucose Absorption in the Jejunum: A Potential Mechanism of the Diabetogenic Effects. PLoS ONE. 2015;10(11):e0143405.
  • Hjelmesaeth J, Hagen LT, Asberg A, et al. The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensitivity in man. Nephrol Dial Transplant. 2007;22(6):1743–1749.
  • Øzbay LA, Møller N, Juhl C, et al. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers. Br J Clin Pharmacol. Internet]. 2012 [cited 2020 Jun 30];73:536–545. Available from (4): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376430/
  • Duijnhoven EM, Boots JM, Christiaans MH, et al. Influence of tacrolimus on glucose metabolism before and after renal transplantation: a prospective study. J Am Soc Nephrol. 2001;12:583–588.
  • Gelens MACJ, van Hooff JP, Usvyat L, et al. No evidence for progressive deterioration in stimulated insulin secretion in renal transplant recipients after 12years tacrolimus exposure. J Diabetes Complicat. 2017;31:1384–1388.
  • Porrini E, Delgado P, Alvarez A, et al. The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation. Nephrol Dial Transplant. 2008;23:1436–1441.
  • Kwan JM, Hajjiri Z, Metwally A, et al. Effect of the Obesity Epidemic on Kidney Transplantation: obesity Is Independent of Diabetes as a Risk Factor for Adverse Renal Transplant Outcomes. PLoS One. Internet]. 2016 [cited 2020 Nov 1];11. Available from (11): e0165712. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112887/
  • Lim SW, Jin L, Jin J, et al. Effect of Exendin-4 on Autophagy Clearance in Beta Cell of Rats with Tacrolimus-induced Diabetes Mellitus. Sci Rep. Internet]. 2016 [cited 2020 Jun 30];6. Available from. ;. (1); https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951772/
  • Øzbay LA, Smidt K, Mortensen DM, et al. Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E beta-cells. Br J Pharmacol. 2011;162(1):136–146.
  • Shaw KT, Ho AM, Raghavan A, et al. Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proc Natl Acad Sci USA. 1995;92:11205–11209.
  • Triñanes J, Rodriguez-Rodriguez AE, Brito-Casillas Y, et al. Deciphering Tacrolimus-Induced Toxicity in Pancreatic β Cells. Am J Transplant. 2017;17(11):2829–2840.
  • Withers DJ, Gutierrez JS, Towery H, et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 1998;391(6670):900–904.
  • Soleimanpour SA, Crutchlow MF, Ferrari AM, et al. Calcineurin signaling regulates human islet {beta}-cell survival. J Biol Chem. 2010;285:40050–40059.
  • Dai C, Walker JT, Shostak A, et al. Tacrolimus- and sirolimus-induced human β cell dysfunction is reversible and preventable. JCI Insight. [Internet]. [ cited 2020 Jun 30];5. Available from. (1). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030815/
  • Drachenberg CB, Klassen DK, Weir MR, et al. Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation. Transplantation. 1999;68(3):396–402.
  • Zelle DM, Corpeleijn E, Deinum J, et al. Pancreatic β-Cell Dysfunction and Risk of New-Onset Diabetes After Kidney Transplantation. Diabetes Care. Internet]. 2013 [cited 2020 Jun 30];36:1926–1932. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687295/
  • HA C, LJ M. Calcineurin Inhibition and New-Onset Diabetes Mellitus After Transplantation. Transplantation. Internet]. 2013 [cited 2020 Jun 30];95. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884894/
  • Wang X, Huong S-M, Chiu ML, et al. Epidermal growth factor receptor is a cellular receptor for human cytomegalovirus. Nature. 2003;424(6947):456–461.
  • Ling Q, Huang H, Han Y, et al. The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: from bench to bedside. Am J Transplant. 2020;20:701–713.
  • Pereira MJ, Palming J, Rizell M, et al. Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell surface in human adipocytes: increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents. J Clin Endocrinol Metab. 2014;99:E1885–1894.
  • Fonseca ACRG, Carvalho E, Eriksson JW, et al. Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018;445:157–168.
  • Rodriguez-Rodriguez AE, Triñanes J, Velazquez-Garcia S, et al. The higher diabetogenic risk of tacrolimus depends on pre-existing insulin resistance A study in obese and lean Zucker rats. Am J Transplant. 2013;13:1665–1675.
  • Almeida CC, Silveira MR, de Araújo VE, et al. Safety of Immunosuppressive Drugs Used as Maintenance Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel). Internet]. 2013 [cited 2020 Jun 30];6:1170–1194. Available from (10): . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817604/
  • Zolota A, Miserlis G, Solonaki F, et al. New-Onset Diabetes After Transplantation: comparison Between a Cyclosporine-Based and a Tacrolimus-Based Immunosuppressive Regimen. Transplant Proc. 2018;50(10):3386–3391.
  • Song J-L, Li M, Yan L-N, et al. Higher tacrolimus blood concentration is related to increased risk of post-transplantation diabetes mellitus after living donor liver transplantation. Int J Surg. 2018;51:17–23.
  • Muduma G, Saunders R, Odeyemi I, et al. Systematic Review and Meta-Analysis of Tacrolimus versus Ciclosporin as Primary Immunosuppression After Liver Transplant. PLoS ONE. 2016;11(11):e0160421.
  • Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357(25):2562–2575.
  • Burroughs TE, Swindle JP, Salvalaggio PR, et al. Increasing Incidence of New-onset Diabetes after Transplant among Pediatric Renal Transplant Patients. Transplantation. Internet]. 2009 [cited 2020 Jun 30];88:367–373. Available from (3): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738606/.
  • Vincenti F, Friman S, Scheuermann E, et al., Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant. 7(6): 1506–1514. 2007. .
  • Liu F-C, Lin H-T, Lin J-R, et al. Impact of immunosuppressant therapy on new-onset diabetes in liver transplant recipients. Ther Clin Risk Manag. Internet]. 2017 [cited 2020 Jun 30];13:1043–1051. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571855/
  • Rathi M, Rajkumar V, Rao N, et al. Conversion from tacrolimus to cyclosporine in patients with new-onset diabetes after renal transplant: an open-label randomized prospective pilot study. Transplant Proc. 2015;47:1158–1161.
  • Wissing KM, Abramowicz D, Weekers L, et al. Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation. Am J Transplant. 2018;18:1726–1734.
  • Sharif A, Shabir S, Chand S, et al. Meta-Analysis of Calcineurin-Inhibitor-Sparing Regimens in Kidney Transplantation. J Am Soc Nephrol. Internet]. 2011 [cited 2020 Jun 30];22:2107–2118. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280000/
  • Karpe KM, Talaulikar GS, Walters GD. Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients. Cochrane Database Syst Rev. Internet]. 2017 [cited 2020 Jun 30 2017 Jun 30];. Available from; . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483545/
  • Song J-L, Gao W, Zhong Y, et al. Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation. World J Gastroenterol. 2016;22:2133–2141.
  • Rostaing L, Bunnapradist S, Grinyó JM, et al. Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: two-Year Results of Phase 3, Double-Blind, Randomized Trial. Am J Kidney Dis. 2016;67:648–659.
  • Barlow AD, Nicholson ML, Herbert TP. Evidence for Rapamycin Toxicity in Pancreatic β-Cells and a Review of the Underlying Molecular Mechanisms. Diabetes. Internet]. 2013 [cited 2020 Jun 30];62:2674–2682. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717855/
  • Fuhrer DK, Kobayashi M, Jiang H. Insulin release and suppression by tacrolimus, rapamycin and cyclosporin A are through regulation of the ATP-sensitive potassium channel. Diabetes Obes Metab. 2001;3:393–402.
  • Bell E, Cao X, Moibi JA, et al. Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets. Diabetes. 2003;52:2731–2739.
  • Hyder A, Laue C, Schrezenmeir J. Effect of the immunosuppressive regime of Edmonton protocol on the long-term in vitro insulin secretion from islets of two different species and age categories. Toxicol In Vitro. 2005;19:541–546.
  • Bussiere CT, Lakey JRT, Shapiro AMJ, et al. The impact of the mTOR inhibitor sirolimus on the proliferation and function of pancreatic islets and ductal cells. Diabetologia. 2006;49:2341–2349.
  • Fraenkel M, Ketzinel-Gilad M, Ariav Y, et al. mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes. 2008;57:945–957.
  • Yang S-B, Lee HY, Young DM, et al. Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J Mol Med. 2012;90:575–585.
  • Yang J, Dolinger M, Ritaccio G, et al. Leucine Stimulates Insulin Secretion via Down-regulation of Surface Expression of Adrenergic α2A Receptor through the mTOR (Mammalian Target of Rapamycin) Pathway. J Biol Chem. Internet]. 2012 [cited 2020 Jun 30];287:24795–24806. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397906/
  • Pereira MJ, Palming J, Rizell M, et al. mTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes. Mol Cell Endocrinol. 2012;355:96–105.
  • Lamming DW, Ye L, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638–1643.
  • Kezic A, Popovic L, Lalic K. mTOR Inhibitor Therapy and Metabolic Consequences: where Do We Stand? Oxid Med Cell Longev. Internet]. 2018 [cited 2020 Nov 6 2018 Nov 6];. Available from; . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035806/
  • Johnston O, Rose CL, Webster AC, et al. Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol. 2008;19:1411–1418.
  • Guerra G, Ciancio G, Gaynor JJ, et al. Randomized Trial of Immunosuppressive Regimens in Renal Transplantation. J Am Soc Nephrol. Internet]. 2011 [cited 2020 Jun 30];22:1758–1768. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171946/
  • Chhabra D, Skaro AI, Leventhal JR, et al. Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens: tacrolimus/Mycophenolate Mofetil versus Tacrolimus/Sirolimus. Clin J Am Soc Nephrol. Internet]. 2012 [cited 2020 Jun 30];7:504–512. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302671/
  • Teutonico A, Schena PF, Di Paolo S. Glucose metabolism in renal transplant recipients: effect of calcineurin inhibitor withdrawal and conversion to sirolimus. J Am Soc Nephrol. 2005;16:3128–3135.
  • Tsang CK, Qi H, Liu LF, et al. Targeting mammalian target of rapamycin (mTOR) for health and diseases. Drug Discov Today. 2007;12:112–124.
  • Veroux M, Tallarita T, Corona D, et al. Conversion to Sirolimus Therapy in Kidney Transplant Recipients with New Onset Diabetes Mellitus after Transplantation. Clin Dev Immunol. [Internet]. 2013 [cited 2020 Jun 30 2013 Jun 30];Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671526/
  • Kälble F, Seckinger J, Schaier M, et al. Switch to an everolimus-facilitated cyclosporine A sparing immunosuppression improves glycemic control in selected kidney transplant recipients. Clin Transplant. 2017;31(8).
  • Nanmoku K, Kurosawa A, Kubo T, et al. Conversion From Steroid to Everolimus in Maintenance Kidney Transplant Recipients With Posttransplant Diabetes Mellitus. Exp Clin Transplant. 2019;17:47–51.
  • Sommerer C, Witzke O, Lehner F, et al.Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials.BMC Nephrol.[Internet]. 2018 [cited 2020 Nov 6];19. Available from;:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146542/.
  • 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;14:2317–2327.
  • Ponticelli C, Arnaboldi L, Moroni G, et al. Treatment of dyslipidemia in kidney transplantation. Expert Opin Drug Saf. 2020;19:257–267.
  • Vega GL, Barlow CE, Grundy SM, et al. Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men. J Investig Med. 2014;62:345–349.
  • Noble J, Jouve T, Janbon B, et al. Belatacept in kidney transplantation and its limitations. Expert Rev Clin Immunol. 2019;15:359–367.
  • Durrbach A, Pestana JM, Florman S, et al. Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidneys: final Results From BENEFIT-EXT, a Phase III Randomized Study. Am J Transplant. 2016;16:3192–3201.
  • Belatacept VF. Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016;374:2600–2601.
  • Vanrenterghem Y, Bresnahan B, Campistol J, et al. Belatacept-based regimens are associated with improved cardiovascular and metabolic risk factors compared with cyclosporine in kidney transplant recipients (BENEFIT and BENEFIT-EXT studies). Transplantation. 2011;91:976–983.
  • Masson P, Henderson L, Chapman JR, et al. Belatacept for kidney transplant recipients. Cochrane Database Syst Rev. 2014;(11):CD010699.
  • Terrec F, Jouve T, Naciri-Bennani H, et al., Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters. Transplant Direct. 6(1): e517. 2020. .
  • Jin L, Lim SW, Jin J, et al. Effect of Conversion to CTLA4Ig on Tacrolimus-Induced Diabetic Rats. Transplantation. 2018;102:e137–e146.
  • Espié P, He Y, Koo P, et al. First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody. Am J Transplant. 2020;20:463–473.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.