Abstract
Preexisting diabetes is common in kidney transplant recipients as it is a leading cause of end-stage renal disease. Hyperglycemia is present in nearly 90% of kidney transplant recipients in immediate postoperative period but it is not sustained in the majority. In addition to the general risk factors for diabetes, certain transplantation related variables (e.g. specific immunosuppressive agents, surgical stress and inflammation, nutritional interventions) place this patient population at elevated risk for hyperglycemia. Preexisting diabetes and posttransplantation diabetes confer reduced patient and graft survival in kidney transplant recipients.
Robust evidence base guiding precise glycemic goals is lacking in kidney transplant recipients. Management is largely guided by evidence from general diabetes population. Hospital management of hyperglycemia is primarily achieved through insulin regimen that takes into account rapid changes in glucocorticoid doses, nutritional modalities, renal function, during immediate posttransplantation period. There is an opportunity to use oral or non-insulin injectable agents in a considerable number of patients by the time of discharge from the hospital or in the long run. Use of specific oral or non-insulin injectable agent is guided by patient specifics and pharmacologic properties of medications. A comprehensive approach to addressing additional risk factors and comorbidities is required to reduce the micro- and macro-vascular complications from diabetes.
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References
American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2018. Diabetes Care. 2018;41.(Supplement 1:S13–27.
Davidson J, Wilkinson A, Dantal J, et al. New-onset diabetes after transplantation: 2003 international consensus guidelines. Transplantation. 2003;75(10):3–24.
Sharif A, Hecking M, de Vries APJ, et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant. 2014;14(9):1992–2000.
Shivaswamy V, Boerner B, Larsen J. Post-transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocr Rev. 2016;37(1):37–61.
Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2015 annual data report: kidney. Am J Transplant. 2017;17(S1):21–116.
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. Transplantation. 2017;101(8):1924–34.
Hecking M, Werzowa J, Haidinger M, et al. Novel views on new-onset diabetes after transplantation: development, prevention and treatment. Nephrol Dial Transplant. 2013;28(3):550–66.
Ghisdal L, Van Laecke S, Abramowicz MJ, Vanholder R, Abramowicz D. New-onset diabetes after renal transplantation: risk assessment and management. Diabetes Care. 2012;35(1):181–8.
Klaassen G, Corpeleijn E, Deetman NPE, Navis GJ, Bakker SJL, Zelle DM. Liver enzymes and the development of Posttransplantation diabetes mellitus in renal transplant recipients. Transplant Direct. 2017;3(9):e208.
Shin J-I, Palta M, Djamali A, Astor BC. Higher pretransplantation hemoglobin A1c is associated with greater risk of posttransplant diabetes mellitus. Kidney Int Reports. 2017;2(6):1076–87.
Visscher PM, Wray NR, Zhang Q, et al. 10 years of GWAS discovery: biology, function, and translation. Am J Hum Genet. 2017;101(1):5–22.
Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010;42(7):579–89.
Fuchsberger C, Flannick J, Teslovich TM, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41–7.
Benson KA, Maxwell AP, McKnight AJ. A HuGE Review and Meta-analyses of genetic associations in new onset diabetes after kidney transplantation. Stepkowski S, ed. PLoS One. 2016;11(1):e0147323.
Dharnidharka VR, Naik AS, Axelrod DA, et al. Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice. Transpl Int. 2018;31(2):198–211.
Hwang JL, Weiss RE. Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment. Diabetes Metab Res Rev. 2014;30(2):96–102. https://doi.org/10.1002/dmrr.2486.
Pirsch JD, Henning AK, First MR, et al. New-onset diabetes after transplantation: results from a double-blind early corticosteroid withdrawal trial. Am J Transplant. 2015;15(7):1982–90.
Haller MC, Royuela A, Nagler EV, Pascual J, Webster AC. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2016;8:CD005632.
Mayer AD, Dmitrewski J, Squifflet JP, et al. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation. 1997;64(3):436–43.
Shapiro R, Jordan M, Fung J, et al. Kidney transplantation under FK 506 immunosuppression. Transplant Proc. 1991;23(1 Pt 2):920–3.
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. 2007;7(6):1506–14.
Sharif A, Shabir S, Chand S, Cockwell P, Ball S, Borrows R. Meta-analysis of calcineurin-inhibitor-sparing regimens in kidney transplantation. J Am Soc Nephrol. 2011;22(11):2107–18.
Øzbay L, Smidt K, Mortensen D, Carstens J, Jørgensen K, Rungby J. Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E beta-cells. Br J Pharmacol. 2011;162(1):136–46.
Triñanes J, Rodriguez-Rodriguez AE, Brito-Casillas Y, et al. Deciphering tacrolimus-induced toxicity in pancreatic β cells. Am J Transplant. 2017;17(11):2829–40.
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. 2007;23(4):1436–41.
Huang JW, Famure O, Li Y, Kim SJ. Hypomagnesemia and the risk of new-onset diabetes mellitus after kidney transplantation. J Am Soc Nephrol. 2016;27(6):1793–800.
Montero N, Pascual J. Immunosuppression and post-transplant hyperglycemia. Curr Diabetes Rev. 2015;11(3):144–54.
Johnston O, Rose CL, Webster AC, Gill JS. Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol. 2008;19(7):1411–8.
Cibrik D, Arcona S, Vasquez E, Baillie GM, Irish W. Long-term experience with everolimus in kidney transplantation in the United States. Transplant Proc. 2011;43(7):2562–7.
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.
Vergès B, Cariou B. mTOR inhibitors and diabetes. Diabetes Res Clin Pract. 2015;110(2):101–8.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. Special issue: KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9:S1–S155.
Stevens RB, Lane JT, Boerner BP, et al. Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia. Clin Transpl. 2012;26(1):123–32.
Aasebo W, Midtvedt K, Valderhaug TG, et al. Impaired glucose homeostasis in renal transplant recipients receiving basiliximab. Nephrol Dial Transplant. 2010;25(4):1289–93.
Morgan RD, O’Callaghan JM, Knight SR, Morris PJ. Alemtuzumab induction therapy in kidney transplantation. Transp J. 2012;93(12):1179–88.
Zheng J, Song W. Alemtuzumab versus antithymocyte globulin induction therapies in kidney transplantation patients. Medicine (Baltimore). 2017;96(28):e7151.
Palermo NE, Gianchandani RY, McDonnell ME, Alexanian SM. Stress hyperglycemia during surgery and anesthesia: pathogenesis and clinical implications. Curr Diab Rep. 2016;16(3):33.
Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–85.
Baid-Agrawal S, Frei U, Reinke P, et al. Impaired insulin sensitivity as an underlying mechanism linking hepatitis C and posttransplant diabetes mellitus in kidney recipients. Am J Transplant. 2009;9(12):2777–84.
Abou-Ayache R, Büchler M, Le Pogamp P, et al. The influence of cytomegalovirus infections on patient and renal graft outcome: a 3-year, multicenter, observational study (post-ECTAZ study). Transplant Proc. 2011;43(7):2630–5.
Revanur VK, Jardine AG, Kingsmore DB, Jaques BC, Hamilton DH, Jindal RM. Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clin Transpl. 2001;15(2):89–94.
Cosio FG, Pesavento TE, Kim S, Osei K, Henry M, Ferguson RM. Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney Int. 2002;62(4):1440–6.
Tillmann FP, Radtke A, Rump LC, Quack I. Effect of prediabetes on allograft survival and evolution of new-onset diabetes after transplant in deceased-donor kidney transplant recipients during long-term follow-up. Exp Clin Transplant. 2017;15(6):620–6.
Valderhaug TG, Hjelmesæth J, Hartmann A, et al. The association of early post-transplant glucose levels with long-term mortality. Diabetologia. 2011;54(6):1341–9.
Wauters RP, Cosio FG, Suarez Fernandez ML, Kudva Y, Shah P, Torres VE. Cardiovascular consequences of new-onset hyperglycemia after kidney transplantation. Transp J. 2012;94(4):377–82.
Eide IA, Halden TAS, Hartmann A, Dahle DO, Åsberg A, Jenssen T. Associations between Posttransplantation diabetes mellitus and renal graft survival. Transplantation. 2017;101(6):1282–9.
Burroughs TE, Swindle J, Takemoto S, et al. Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients. Transplantation. 2007;83(8):1027–34.
American Diabetes Association AD. 10. Microvascular complications and foot care: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S105–18.
Lo C, Jun M, Badve SV, et al. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2017;2:CD009966.
Sathya B, Davis R, Taveira T, Whitlatch H, Wu W-C. Intensity of peri-operative glycemic control and postoperative outcomes in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract. 2013;102(1):8–15.
American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S144–51.
Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(1):16–38.
Smiley D, Rhee M, Peng L, et al. Safety and efficacy of continuous insulin infusion in noncritical care settings. J Hosp Med. 2010;5(4):212–7.
Schmeltz L, DeSantis A, Schmidt K, et al. Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia. Endocr Pract. 2006;12(6):641–50.
Hsia E, Seggelke S, Gibbs J, et al. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012;97(9):3132–7.
Casaer MP, Ziegler TR. Nutritional support in critical illness and recovery. Lancet Diabetes Endocrinol. 2015;3(9):734–45.
Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE/ACE comprehensive diabetes management algorithm 2015. Endocr Pract. 2015;21(4):438–47.
O’Malley CW, Emanuele M, Halasyamani L, Amin AN, Society of Hospital Medicine Glycemic Control Task Force. Bridge over troubled waters: safe and effective transitions of the inpatient with hyperglycemia. J Hosp Med. 2008;3(5 Suppl):55–65.
Umpierrez GE, Smiley D, Jacobs S, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery). Diabetes Care. 2011;34(2):256–61.
Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-induced hyperglycemia. Am J Med Sci. 2013;345(4):274–7.
Dhital S, Shenker Y, Meredith M, Davis D. A retrospective study comparing neutral protamine hagedorn insulin with glargine as basal therapy in prednisone-associated diabetes mellitus in hospitalized patients. Endocr Pract. 2012;18(5):712–9.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of Hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–9.
American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S73–85.
Stephen J, Anderson-Haag TL, Gustafson S, Snyder JJ, Kasiske BL, Israni AK. Metformin use in kidney transplant recipients in the United States: an observational study. Am J Nephrol. 2014;40(6):546–53.
Halden TAS, Egeland EJ, Åsberg A, et al. GLP-1 restores altered insulin and glucagon secretion in posttransplantation diabetes. Diabetes Care. 2016;39(4):617–24.
Pinelli NR, Patel A, Salinitri FD. Coadministration of liraglutide with tacrolimus in kidney transplant recipients: a case series. Diabetes Care. 2013;36(10):e171–2.
Kharazmkia A, Ahmadpoor P, Ziaei S, et al. Effects of pioglitazone on blood glucose and inflammatory markers of diabetic kidney transplant patients: a randomized controlled trial. Iran J Kidney Dis. 2014;8(5):408–16.
Werzowa J, Hecking M, Haidinger M, et al. Vildagliptin and pioglitazone in patients with impaired glucose tolerance after kidney transplantation: a randomized, placebo-controlled clinical trial. Transplantation. 2013;95(3):456–62.
Pietruck F, Kribben A, Van TN, et al. Rosiglitazone is a safe and effective treatment option of new-onset diabetes mellitus after renal transplantation. Transpl Int. 2005;18(4):483–6.
Haidinger M, Werzowa J, Hecking M, et al. Efficacy and safety of vildagliptin in new-onset diabetes after kidney transplantation-a randomized, double-blind, placebo-controlled trial. Am J Transplant. 2014;14(1):115–23.
Lane JT, Odegaard DE, Haire CE, Collier DS, Wrenshall LE, Stevens RB. Sitagliptin therapy in kidney transplant recipients with new-onset diabetes after transplantation. Transplantation. 2011;92(10):e56–7.
Strom Halden TA, Asberg A, Vik K, Hartmann A, Jenssen T. Short-term efficacy and safety of sitagliptin treatment in long-term stable renal recipients with new-onset diabetes after transplantation. Nephrol Dial Transplant. 2014;29(4):926–33.
Boerner BP, Miles CD, Shivaswamy V. Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation. Int J Endocrinol. 2014;2014:1–9.
Chidester PD, Connito DJ. Interaction between glipizide and cyclosporine: report of two cases. Transplant Proc. 1993;25(2):2136–7.
Sagedal S, Asberg A, Hartmann A, Bergan S, Berg KJ. Glipizide treatment of post-transplant diabetes does not interfere with cyclosporine pharmacokinetics in renal allograft recipients. Clin Transpl. 1998;12(6):553–6.
Tuerk TR, Bandur S, Nuernberger J, et al. Gliquidone therapy of new-onset diabetes mellitus after kidney transplantation. Clin Nephrol. 2008;70(1):26–32.
Türk T, Pietruck F, Dolff S, et al. Repaglinide in the management of new-onset diabetes mellitus after renal transplantation. Am J Transplant. 2006;6(4):842–6.
American Diabetes Association. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S28–37.
American Diabetes Association. Lifestyle management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S38–50.
Sharif A, Moore R, Baboolal K. Influence of lifestyle modification in renal transplant recipients with postprandial hyperglycemia. Transplantation. 2008;85(3):353–8.
Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677–86.
Lindström J, Ilanne-Parikka P, Peltonen M, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006;368(9548):1673–9.
Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371(9626):1783–9.
American Diabetes Association. Prevention or delay of type 2 diabetes: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S51–4.
Gazzetta PG, Bissolati M, Saibene A, et al. Bariatric surgery to target obesity in the renal transplant population: preliminary experience in a single center. Transplant Proc. 2017;49(4):646–9.
Viscido G, Gorodner V, Signorini FJ, et al. Sleeve gastrectomy after renal transplantation. Obes Surg. 2018;28:1587–94.
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Dhital, S.M. (2019). Diabetes in Kidney Transplant Recipients. In: Parajuli, S., Aziz, F. (eds) Kidney Transplant Management. Springer, Cham. https://doi.org/10.1007/978-3-030-00132-2_10
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