COVID-19 | Discover the latest peer-reviewed research articles from the Eastern Mediterranean Region
COVID-19 | Discover the latest peer-reviewed research articles from the Eastern Mediterranean Region
COVID-19 | Discover the latest publications published by WHO Regional Office for the Eastern Mediterranean
COVID-19 | Discover the latest publications published by WHO Regional Office for the Eastern Mediterranean

Effect of sirolimus as an immunosuppressive agent on kidney transplantation in patients with diabetes mellitus; a systematic review
Davar, Saeedeh
Rahimi, Mohsen Mohammad
Akhgar, Maasoumeh Mahdi
Saei, Sajjad
Urmia University of Medical Sciences, , Department of Biostatistics and Epidemiology

J. Nephropathol. 2020; 9 (2): 1[e13]-6
JNP-Journal of Nephropathology
Journal Country: Islamic Republic of Iran
P-ISSN: 2251-8363
E-ISSN: 2251-8819
Type of Publication: Systematic Review
Category: Humans,
Type of Research: Clinical
Indexing Status : Archived
Broad Subjects: Pharmaceutical Products,
Citation: Saeedeh Davar, Mohsen Mohammad Rahimi, Maasoumeh Mahdi Akhgar, Sajjad Saei, Effect of sirolimus as an immunosuppressive agent on kidney transplantation in patients with diabetes mellitus; a systematic review. J. Nephropathol. 2020; 9 (2): 1[e13]-6 . https://doi.org/10.34172/jnp.2020.13

Introduction: Sirolimus is a macrolide and a type of immunosuppressant drug to prevent rejection of transplanted organs. This drug inhibits the activation of T and B lymphocytes and reduces the production of interleukin-2 (IL-2)
Objectives: This study aimed to review the effect of sirolimus in kidney transplantation in patients with diabetes mellitus as a systematic review
Materials and Methods: International databases including PubMed, Web of Science and Scopus were considered for search of English articles by 29 June 2019. Twenty-one published articles were finally entered into the study. Keywords were sirolimus, rapamune, rapamycin, diabetes mellitus and kidney transplantation or a combination of them in the title/abstracts. Treatment using a combination of sirolimus and tacrolimus were excluded
Results: There were more than 3244 subjects reviewed in this systematic review including 21 published articles (Total population of 21 articles: 3244 people)
Conclusion: According to the results, sirolimus-based immunosuppression for preventing kidney transplantation is effective and has a low-risk in diabetic patients resulting in suitable glucose control

  1. Zhang Q-L, Rothenbacher D. Prevalence of chronic kidney disease in population-base d studies: systematic review. BMC Public Health. 2008;8:117. doi: 10.1186/1471-2458-8-117.
  2. Harrison TR, Kasper DL. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005.
  3. Shaheen FA, Al-Khader AA. Epidemiology and causes of end stage renal disease (ESRD). Saudi J Kidney Dis Transpl. 2005;16:277-81.
  4. Hsu CY, Iribarren C, McCulloch CE, Darbinian J, Go AS. Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med. 2009;169:342-50. doi: 10.1001/ archinternmed.2008.605.
  5. Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M, Alberta Kidney Disease Network. Renal replacement therapy in patients with acute renal failure: a systematic review. JAMA. 2008;299:793-805. doi: 10.1001/jama.299.7.793
  6. Chkhotua A, Pantsulaia T, Managadze L. The quality of life analysis in renal transplant recipients and dialysis patients. Georgian Med News. 2011;11:10-7.
  7. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351:2715-29. doi: 10.1056/NEJMra033540
  8. Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. 2010;363:1451-62. doi: 10.1056/ NEJMra0902927.
  9. Sehgal SN. Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003; 35:7S-14S. doi: 10.1016/s0041-1345(03)00211-2.
  10. 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. doi: 10.1681/ASN.2007111202.
  11. Asrani SK, Leise MD, West CP, Murad MH, Pedersen RA, Erwin PJ, Tian J, Wiesner RH, Kim WR. Use of sirolimus in liver transplant recipients with renal insufficiency: A systematic review and meta‐ Hepatology. 2010; 52:1360-70. doi: 10.1002/hep.23835.
  12. Webster AC, Lee VW, Chapman JR, Craig JC. Target of rapamycin inhibitors (sirolimus and everolimus) for primary immunosuppression of kidney transplant recipients: a systematic review and meta-analysis of randomized trials. Transplantation. 2006;81:1234-48. doi: 10.1097/01. tp.0000219703.39149.85.
  13. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.
  14. Centre for Reviews and Dissemination: Systematic reviews: CRD’s 16 guidance for undertaking reviews in health care. York: University of York; 2009.
  15. Almeida M, Martins LS, Dias L, Figueiredo MJ, Henriques AC, Sarmento AM, et al. Conversion to sirolimus in a population of kidney and kidney-pancreas transplant recipients. Transplant Proc. 2005;37:2777-80. doi: 10.1016/j.transproceed.2005.06.088
  16. Anil Kumar MS, Heifets M, Fyfe B, Saaed MI, Moritz MJ, Parikh MH, et al. Comparison of steroid avoidance in tacrolimus/mycophenolate mofetil and tacrolimus/sirolimus combination in kidney transplantation monitored by surveillance biopsy. Transplantation. 2005;80:807-14. doi: 10.1097/01.tp.0000173378.28790.0b
  17. Arellano EM, Campistol JM, Oppenheimer F, Rovira J, Diekmann F. Sirolimus monotherapy as maintenance immunosuppression: single-center experience in 50 kidney transplant patients. Transplant Proc. 2007;39:2131-4. doi: 10.1016/j.transproceed.2007.06.056
  18. Ciancio G, Burke GW, Gaynor JJ, Ruiz P, Roth D, Kupin W, et al. A randomized long-term trial of tacrolimus/ sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis. Transplantation. 2006;81:845-52. doi: 10.1097/01. tp.0000203894.53714.27
  19. Ferreira AN, Machado PG, Felipe CR, Motegi SA, Hosaka BH, Tanaka MK, et al. Concentration-controlled use of sirolimus associated with reduced exposure of cyclosporine in black recipients of primarily living renal allograft donors: 12-month results. Clin Transplant. 2005;19:607-15. doi: 10.1111/j.1399-0012.2005.00331.x.
  20. Gatault P, Bertrand D, Buchler M, Colosio C, Hurault de Ligny B, Weestel PF, et al. Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation. Transplant Int. 2016;29:41-50. doi:10.1111/tri.12656
  21. Gyurus E, Kaposztas Z, Kahan BD. Sirolimus therapy predisposes to new-onset diabetes mellitus after renal transplantation: a long-term analysis of various treatment regimens. Transplant Proc. 2011;43:1583-92. doi: 10.1016/j. transproceed.2011.05.001.
  22. Havrdova T, Saudek F, Boucek P, Adamec M, Koznarova R, Jedinakova T, et al. Metabolic effect of sirolimus versus mycophenolate mofetil on pancreatic graft function in the early posttransplant period. Transplant Proc. 2005;37:3544- 5. doi: 10.1016/j.transproceed.2005.09.056
  23. Jaber JJ, Feustel PJ, Elbahloul O, Conti AD, Gallichio MH, Conti DJ. Early steroid withdrawal therapy in renal transplant recipients: a steroid-free sirolimus and CellCept-based calcineurin inhibitor-minimization protocol. Clin Transplant. 2007;21:101-9. doi: 10.1111/j.1399- 0012.2006.00613.x
  24. Johnston O, Rose CL, Webster AC, Gill JS. Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol. 2008;19:1411-8. doi: 10.1681/ASN.2007111202.
  25. Kahan BD, Julian BA, Pescovitz MD, Vanrenterghem Y, Neylan J. Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. Transplantation. 1999; 68:1526-32. doi: 10.1097/00007890-199911270-00016
  26. Legendre C, Campistol JM, Squifflet JP, Burke JT. Cardiovascular risk factors of sirolimus compared with cyclosporine: early experience from two randomized trials in renal transplantation. Transplant Proc. 2003; 35:151s-3s. doi: 10.1016/s0041-1345(03)00241-0
  27. Mital D, Podlasek W, Jensik SC. Sirolimus-based steroid-free maintenance immunosuppression. Transplant Proc. 2002; 34:1709-10. doi: 10.1016/S0041-1345(02)02992-5
  28. Podder H, Forgacs B, Csapo Z, Kahan B. [Improved outcome with sirolimus-cyclosporine regimen in high-risk renal transplant recipients]. Orvo Hetil. 2005;146:1641-6.
  29. Romagnoli J, Citterio F, Nanni G, Favi E, Tondolo V, Spagnoletti G, et al. Incidence of posttransplant diabetes mellitus in kidney transplant recipients immunosuppressed with sirolimus in combination with cyclosporine. Transplant Proc. 2006;38:1034-6. doi: 10.1016/j. transproceed.2006.03.072
  30. Steigerwalt SP, Brar N, Dhungel A, Butcher D, Steigerwalt S, El-Ghouroury M, et al. Improved 24-hour blood pressure control with sirolimus versus calcineurin inhibitor based immunosuppression in renal transplant recipients. Transplant Proc. 2009;41:4184-7. doi: 10.1016/j. transproceed.2009.07.109.
  31. Sundberg AK, Rohr MS, Hartmann EL, Adams PL, Stratta RJ. Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients. Clin Transplant. 2004; 18 Suppl 12:61-6. doi: 10.1111/j.1399-0012.2004.00220.x
  32. Veroux M, Tallarita T, Corona D, Sinagra N, Giaquinta A, Zerbo D, et al. Conversion to sirolimus therapy in kidney transplant recipients with new onset diabetes mellitus after transplantation. Clinical & developmental immunology. 2013; 2013:496974. Clin Dev Immunol. 2013; 2013:496974. doi: 10.1155/2013/496974.
  33. 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;16:3128-35. doi: 10.1681/ASN.2005050487
  34. Veroux M, Corona D, Giuffrida G, Gagliano M, Vizcarra D, Tallarita T, et al. Sirolimus-based immunosuppression in kidney transplantation for type 2 diabetic nephropathy. Urol Int. 2010;84:301-4. doi: 10.1159/000288232.
  35. Lebranchu Y, Thierry A, Thervet E, Büchler M, Etienne I, Westeel PF, et al. Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF—four-year results of the Postconcept study. AM J Transplant. 2011; 11:1665-75. doi: 10.4103/0971-4065.176146
  36. Fleming GM. Renal replacement therapy review: past, present and future. Organogenesis. 2011;7:2-12. doi: 10.4161/org.7.1.13997
  37. Saturnino LTM, Ceccato MGB, Cherchiglia ML, Andrade ELG, Giordano LFC, Acurcio FA. Target of rapamycin inhibitors (TORi) as maintenance immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev 2015;3:CD009637. doi: 10.1002/14651858.CD004290. pub2
  38. Pascual J, Zamora J, Galeano C, Royuela A, Quereda C. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2009;(1):CD005632. doi: 10.1002/14651858.CD005632.pub2
  39. Cooper JE, Christians U, Wiseman AC. Everolimus in kidney transplantation. Transplant Res Risk Manag. 2011;3: 97-112.
  40. Araki M, Flechner SM, Ismail HR, Flechner LM, Zhou L, Derweesh IH, et al. Posttransplant diabetes mellitus in kidney transplant recipients receiving calcineurin or mTOR inhibitor drugs. Transplantation 2006;81:335-41. doi: 10.1097/01.tp.0000195770.31960.18
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