Immunosuppressive Drugs and Kidney Post-transplant Diabetes Mellitus

Document Type: Original Article

Authors

1 College of Nursing, Hawler Medical University, Erbil, Iraq

2 Biology Department, College of Education,Salahaddin University-Erbil, Erbil, Iraq

Abstract

Background: As the rate of renal transplantation increases, more immunosuppressive drugs such as cyclosporine A (CsA) are consumed, particularly during the early months following transplantation, leading to post-transplant diabetes mellitus (PTDM) which can cause death.
Objective: The present study examined the role of CsA in causing PTDM and other effective factors among patients with chronic kidney disease (CKD) who had undergone renal replacement therapy.
Methods: The present investigation was a quantitative case-control study carried out on 30 CKD patients who had undergone renal transplantation and 30 healthy individuals. A questionnaire was utilized to gather their demographic information, and direct interviews were conducted with the subjects. To examine random blood sugar (RBS), white blood cell (WBC) count, creatinine level, and blood urea nitrogen (BUN), blood samples were obtained from the subjects. The mentioned parameters were analyzed using SPSS 22.0.
Results: According to the results, the groups were homogenous in age, body mass index (BMI), and male-to-female ratio. However, there were significant differences between the two groups in RBS (P = 0.011), WBC count (P = 0.031), creatinine level (P = 0.001), and BUN (P = 0.001).
Conclusion: Failure of allograft survival of renal transplantation was found to be a leading cause of death, which has been reportedly been treated by the consumption of immunosuppressive drugs such as CsA. However, this drug can increase the patient’s chances of developing PTDM. PTDM development can be reduced by applying a dosage of 10 mg/kg/d during the first week and 8-9 mg/kg/day during weeks 2-5 following transplantation.

Keywords


  1. Sarno G, Muscogiuri G, De Rosa P. New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation. 2012;93(12):1189-1195. doi:10.1097/TP.0b013e31824db97d.
  2. Chadban S. New-onset diabetes after transplantation--should it be a factor in choosing an immunosuppressant regimen for kidney transplant recipients. Nephrol Dial Transplant. 2008;23(6):1816-1818. doi:10.1093/ndt/gfn052.
  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):1506-1514. doi:10.1111/j.1600-6143.2007.01749.x.
  4. Roth D, Milgrom M, Esquenazi V, Fuller L, Burke G, Miller J. Posttransplant hyperglycemia. Increased incidence in cyclosporine-treated renal allograft recipients. Transplantation. 1989;47(2):278-281. doi:10.1097/00007890-198902000-00016.
  5. Vesco L, Busson M, Bedrossian J, Bitker MO, Hiesse C, Lang P. Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors. Transplantation. 1996;61(10):1475-1478. doi:10.1097/00007890-199605270-00011.
  6. Lindholm A, Albrechtsen D, Frodin L, Tufveson G, Persson NH, Lundgren G. Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia. Transplantation. 1995;60(5):451-457. doi:10.1097/00007890-199509000-00008.
  7. Friedman EA, Shyh TP, Beyer MM, Manis T, Butt KM. Posttransplant diabetes in kidney transplant recipients. Am J Nephrol. 1985;5(3):196-202. doi:10.1159/000166932.
  8. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178-185. doi:10.1034/j.1600-6143.2003.00010.x.
  9. Sumrani NB, Delaney V, Ding ZK, et al. Diabetes mellitus after renal transplantation in the cyclosporine era--an analysis of risk factors. Transplantation. 1991;51(2):343-347. doi:10.1097/00007890-199102000-00014.
  10. Boudreaux JP, McHugh L, Canafax DM, et al. The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients. Transplantation. 1987;44(3):376-381. doi:10.1097/00007890-198709000-00010.
  11. Sampaio EL, Pinheiro-Machado PG, Garcia R, et al. Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen. Clin Transplant. 2008;22(2):141-149. doi:10.1111/j.1399-0012.2007.00756.x.
  12. Weir MR, Fink JC. Risk for posttransplant Diabetes mellitus with current immunosuppressive medications. Am J Kidney Dis. 1999;34(1):1-13. doi:10.1016/S0272-6386(99)70101-0.
  13. 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. doi:10.1097/00007890-199908150-00012.
  14. Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation. 1997;63(7):977-983. doi:10.1097/00007890-199704150-00013.
  15. 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):436-443. doi:10.1097/00007890-199708150-00012.
  16. Silva F, Queiros J, Vargas G, Henriques A, Sarmento A, Guimaraes S. Risk factors for posttransplant diabetes mellitus and impact of this complication after renal transplantation. Transplant Proc. 2000;32(8):2609-2610. doi:10.1016/S0041-1345(00)01805-4.
  17. Hathaway DK, Tolley EA, Blakely ML, Winsett RP, Gaber AO. Development of an index to predict posttransplant diabetes mellitus. Clin Transplant. 1993;7(4):330-338.
  18. Jindal RM. Posttransplant diabetes mellitus--a review. Transplantation. 994;58(12):1289-1298.
  19. Danovitch GM. Immunosuppressive medications for renal transplantation: a multiple choice question. Kidney Int. 2001;59(1):388-402. doi:10.1046/j.1523-1755.2001.00501.x.
  20. Muntean A, Lucan M. Immunosuppression in kidney transplantation. Clujul Med. 2013;86(3):177-180.
  21. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000;342(9):605-612. doi:10.1056/NEJM200003023420901.
  22. Ojo AO, Hanson JA, Wolfe RA, Leichtman AB, Agodoa LY, Port FK. Long-term survival in renal transplant recipients with graft function. Kidney Int. 2000;57(1):307-313. doi:10.1046/j.1523-1755.2000.00816.x.
  23. Cosio FG, Alamir A, Yim S, et al. Patient survival after renal transplantation: I. The impact of dialysis pre-transplant. Kidney Int. 1998;53(3):767-772. doi:10.1046/j.1523-1755.1998.00787.x.
  24. USRDS: United States Renal Data System 1996 annual data report. Am J Kidney Dis. 1996;28:S1-S152.
  25. Cosio FG, Kudva Y, van der Velde M, et al. New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int. 2005;67(6):2415-2421. doi:10.1111/j.1523-1755.2005.00349.x.
  26. Liefeldt L, Budde K. Risk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk. Transpl Int. 2010;23(12):1191-1204. doi:10.1111/j.1432-2277.2010.01159.x.
  27. Rodrigo E, Fernandez-Fresnedo G, Valero R, et al. New-onset diabetes after kidney transplantation: risk factors. J Am Soc Nephrol. 2006;17(12 Suppl 3):S291-295. doi:10.1681/ASN.2006080929.
  28. Gourishankar S, Jhangri GS, Tonelli M, Wales LH, Cockfield SM. Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant. 2004;4(11):1876-1882. doi:10.1111/j.1600-6143.2004.00591.x.
  29. Peev V, Reiser J, Alachkar N. Diabetes mellitus in the transplanted kidney. Front Endocrinol (Lausanne). 2014;5:141. doi:10.3389/fendo.2014.00141.
  30. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178-185. doi:10.1034/j.1600-6143.2003.00010.x.
  31. Davidson J, Wilkinson A, Dantal J, et al. New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation. 2003;75(10 Suppl):Ss3-24. doi:10.1097/01.TP.0000069952.49242.3E.
  32. Kaposztas Z, Gyurus E, Kahan BD. New-onset diabetes after renal transplantation: diagnosis, incidence, risk factors, impact on outcomes, and novel implications. Transplant Proc. 2011;43(5):1375-1394. doi:10.1016/j.transproceed.2011.04.008.
  33. Cosio FG, Hickson LJ, Griffin MD, Stegall MD, Kudva Y. Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes. Am J Transplant. 2008;8(3):593-599. doi:10.1111/j.1600-6143.2007.02101.x.
  34. Shivaswamy V, Boerner B, Larsen J. Post-transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocr Rev. 2016;37(1):37-61. doi:10.1210/er.2015-1084.
  35. Seifi S, Rahbar M, Lessan-Pezeshki M, et al. Posttransplant diabetes mellitus: incidence and risk factors. Transplant Proc. 2009;41(7):2811-2813. doi:10.1016/j.transproceed.2009.07.043.
  36. Choi JY, Kwon OJ. Post-transplant diabetes mellitus: is it associated with poor allograft outcomes in renal transplants? Transplant Proc. 2013;45(8):2892-2898. doi:10.1016/j.transproceed.2013.08.067.
  37. Helfritz FA, Lehner F, Manns MP, Ciesek S, Klempnauer J. Perioperative white blood cell count as a marker for patient and graft survival after orthotopic liver transplantation. J Hepatol Gastroint Dis. 2015;1(1):1-5.
  38. American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care. 2015;38 Suppl:S8-s16. doi:10.2337/dc15-S005.
  39. World Health Organization (WHO). Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Report of a WHO/IDF Consultation. Geneva, Switzerland: WHO; 2006.
  40. Keane WF, Kasiske BL. Hyperlipidemia in the nephrotic syndrome. N Engl J Med. 1990;323(9):603-604. doi:10.1056/NEJM199008303230910.
  41. Attman PO, Samuelsson O, Alaupovic P. Lipoprotein metabolism and renal failure. Am J Kidney Dis. 1993;21(6):573- 592. doi:10.1016/S0272-6386(12)80030-8.
  42. Markell MS, Armenti V, Danovitch G, Sumrani N. Hyperlipidemia and glucose intolerance in the post-renal transplant patient. J Am Soc Nephrol. 1994;4(8 Suppl):S37-47.
  43. Massy ZA, Kasiske BL. Hyperlipidemia and its management in renal disease. Curr Opin Nephrol Hypertens. 1996;5(2):141-146. doi:10.1097/00041552-199603000-00007.
  44. Mittman N, Avram MM. Dyslipidemia in renal disease. Semin Nephrol. 1996;16(3):202-213.
  45. Sutherland WH, Walker RJ, Ball MJ, Stapley SA, Robertson MC. Oxidation of low density lipoproteins from patients with renal failure or renal transplants. Kidney Int. 1995;48(1):227-236. doi:10.1038/ki.1995.288.
  46. Ong CS, Pollock CA, Caterson RJ, Mahony JF, Waugh DA, Ibels LS. Hyperlipidemia in renal transplant recipients: natural history and response to treatment. Medicine (Baltimore). 1994;73(4):215-223. doi:10.1097/00005792-199407000-00004.
  47. Bagdade J, Casaretto A, Albers J. Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man. J Lab Clin Med. 1976;87(1):38-48. doi:10.5555/uri:pii:0022214376903280.
  48. First MR. Long-term Complications After Transplantation. Am J Kidney Dis. 1993;22(3):477-486. doi:10.1016/S0272-6386(12)70156-7.
  49. Vathsala A, Weinberg RB, Schoenberg L, et al. Lipid abnormalities in cyclosporine-prednisone-treated renal transplant recipients. Transplantation. 1989;48(1):37-43. doi:10.1097/00007890-198907000-00009.
  50. Hill MN, Grossman RA, Feldman HI, Hurwitz S, Dafoe DC. Changes in causes of death after renal transplantation, 1966 to 1987. Am J Kidney Dis. 1991;17(5):512-518. doi:10.1016/S0272-6386(12)80491-4.
  51. Braun WE, Marwick TH. Coronary artery disease in renal transplant recipients. Cleve Clin J Med. 1994;61(5):370-385. doi:10.3949/ccjm.61.5.370.
  52. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA. 1993;269(23):3015-3023. doi:10.1001/jama.1993.03500230097036.
  53. Rosenbaum R, Hoffsten PE, Cryer P, Klahr S. Hyperkalemia after renal transplantation. Occurrence in a patient with insulin-dependent diabetes. Arch Intern Med. 1978;138(8):1270- 1272. doi:10.1001/archinte.1978.03630330070020.
  54. Kaplan B, Wang Z, Abecassis MM, Fryer JP, Stuart FP, Kaufman DB. Frequency of hyperkalemia in recipients of simultaneous pancreas and kidney transplants with bladder drainage. Transplantation. 1996;62(8):1174-1175. doi:10.1097/00007890-199610270-00025.
  55. Higgins R, Ramaiyan K, Dasgupta T, et al. Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities. Nephrol Dial Transplant. 2004;19(2):444- 450. doi:10.1093/ndt/gfg515.