J Reconstr Microsurg 2012; 28(01): 07-20
DOI: 10.1055/s-0031-1285988
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Impact of Current Immunosuppression Strategies in Renal Transplantation on the Field of Reconstructive Transplantation

Jeff Chang
1   Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Washington, Seattle, Washington
,
Connie L. Davis
2   Department of Medicine, University of Washington, Seattle, Washington
,
David W. Mathes
1   Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Washington, Seattle, Washington
› Author Affiliations
Further Information

Publication History

16 May 2011

30 May 2011

Publication Date:
12 August 2011 (online)

Abstract

Composite tissue allograft (CTA) transplantation, such as the clinical face and hand transplants, has now been performed in multiple centers across the world. The transplants have successfully treated complex injuries that have either failed conventional approaches or where autologous reconstruction could not restore both form and function. CTA transplantation has the potential to improve outcomes over traditional techniques. However, the widespread application of CTA transplantation continues to be limited by the need for chronic immunosuppression. Due to the small numbers of CTA transplants performed, any modification in the immunosuppression used will likely be based from the solid organ literature. The renal transplantation literature has served as the basis for the current selection of CTA drug regimens and in this article we review the evidence in the renal transplant literature for the selection of immunosuppressive regimens. The study then compares the regimens used in both the face and hand transplantation with those regimens currently used for renal transplantation.

 
  • References

  • 1 Garcia VD, Carvalho DB, Gonçalves RT , et al. Randomized trial of early corticosteroid reduction vs. regular-dose corticosteroid maintenance in combination with tacrolimus and mycophenolate mofetil in living donor kidney transplant recipients: the Brazilian CORRETA trial. Clin Transplant 2010; 24 (4) E109-E115
  • 2 Merrill JP, Murray JE, Harrison JH, Guild WR. Successful homotransplantation of the human kidney between identical twins. J Am Med Assoc 1956; 160 (4) 277-282
  • 3 Whitaker IS, Duggan EM, Alloway RR , et al. Composite tissue allotransplantation: a review of relevant immunological issues for plastic surgeons. J Plastic Reconstr Aesthet Surg 2008; 61 (5) 481-492
  • 4 Forsythe JL. ATG—a polyclonal sledgehammer?. Transpl Immunol 1994; 2 (2) 148-152
  • 5 Vincenti F, Kirkman R, Light S , et al. Daclizumab Triple Therapy Study Group Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 1998; 338 (3) 161-165
  • 6 Hardinger KL, Rhee S, Buchanan P , et al. A prospective, randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy: 10-year results. Transplantation 2008; 86 (7) 947-952
  • 7 Cantarovich M, Durrbach A, Hiesse C, Ladouceur M, Benoit G, Charpentier B. 20-year follow-up results of a randomized controlled trial comparing antilymphocyte globulin induction to no induction in renal transplant patients. Transplantation 2008; 86 (12) 1732-1737
  • 8 Tian JH, Wang X, Yang KH, Liu AP, Luo XF, Zhang J. Induction with and without antithymocyte globulin combined with cyclosporine/tacrolimus-based immunosuppression in renal transplantation: a meta-analysis of randomized controlled trials. Transplant Proc 2009; 41 (9) 3671-3676
  • 9 Calne R, Friend P, Moffatt S , et al. Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet 1998; 351 (9117) 1701-1702
  • 10 Ciancio G, Burke III GW. Alemtuzumab (Campath-1H) in kidney transplantation. Am J Transplant 2008; 8 (1) 15-20
  • 11 Farney A, Sundberg A, Moore P , et al. A randomized trial of alemtuzumab vs. anti-thymocyte globulin induction in renal and pancreas transplantation. Clin Transplant 2008; 22 (1) 41-49
  • 12 Schadde E, D'Alessandro AM, Knechtle SJ , et al. Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death. Transpl Int 2008; 21 (7) 625-636
  • 13 Ciancio G, Burke GW, Gaynor JJ , et al. A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow-up. Clin Transplant 2008; 22 (2) 200-210
  • 14 Ciancio G, Gaynor JJ, Roth D , et al. Randomized trial of thymoglobulin versus alemtuzumab (with lower dose maintenance immunosuppression) versus daclizumab in living donor renal transplantation. Transplant Proc 2010; 42 (9) 3503-3506
  • 15 Thomas PG, Woodside KJ, Lappin JA, Vaidya S, Rajaraman S, Gugliuzza KK. Alemtuzumab (Campath 1H) induction with tacrolimus monotherapy is safe for high immunological risk renal transplantation. Transplantation 2007; 83 (11) 1509-1512
  • 16 Tan HP, Donaldson J, Basu A , et al. Two hundred living donor kidney transplantations under alemtuzumab induction and tacrolimus monotherapy: 3-year follow-up. Am J Transplant 2009; 9 (2) 355-366
  • 17 Kandus A, Arnol M, Omahen K , et al. Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal transplantation: a prospective, randomized study. Transplantation 2010; 89 (8) 1022-1027
  • 18 Webster AC, Ruster LP, McGee R , et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev 2010; (1): CD003897-
  • 19 Laftavi MR, Alnimri M, Weber-Shrikant E , et al. Low-dose rabbit antithymocyte globulin versus basiliximab induction therapy in low-risk renal transplant recipients: 8-year follow-up. Transplant Proc 2011; 43 (2) 458-461
  • Immunosuppression Use for Induction. 1999 to 2008 Recipients with Kidney Transplants. (2009). SRTR Database. Retrieved from http://optn.transplant.hrsa.gov/ar2009/506a_ki.htm
  • 21 Webster AC, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ 2005; 331 (7520) 810-
  • 22 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 (9) 1234-1248
  • 23 Weir MR, Mulgaonkar S, Chan L , et al. Mycophenolate mofetil-based immunosuppression with sirolimus in renal transplantation: a randomized, controlled Spare-the-Nephron trial. Kidney Int 2011; 79 (8) 897-907
  • 24 Vincenti F, Schena FP, Paraskevas S, Hauser IA, Walker RG, Grinyo J. FREEDOM Study Group. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant 2008; 8 (2) 307-316
  • 25 Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P ; Astellas Corticosteroid Withdrawal Study Group 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 (4) 564-577
  • 26 Augustine JJ, Hricik DE. Steroid withdrawal: moving on to the next questions. Am J Transplant 2009; 9 (1) 3-4
  • 27 Luan FL, Steffick DE, Gadegbeku C, Norman SP, Wolfe R, Ojo AO. Graft and patient survival in kidney transplant recipients selected for de novo steroid-free maintenance immunosuppression. Am J Transplant 2009; 9 (1) 160-168
  • 28 Padiyar A, Augustine JJ, Bodziak KA, Aeder M, Schulak JA, Hricik DF. Influence of African-American ethnicity on acute rejection after early steroid withdrawal in primary kidney transplant recipients. Transplant Proc 2010; 42 (5) 1643-1647
  • 29 Laftavi MR, Stephan R, Stefanick B , et al. Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety. Surgery 2005; 137 (3) 364-371
  • 30 Heilman RL, Reddy KS, Mazur MJ , et al. Acute rejection risk in kidney transplant recipients on steroid-avoidance immunosuppression receiving induction with either antithymocyte globulin or basiliximab. Transplant Proc 2006; 38 (5) 1307-1313
  • 31 Heilman RL, Chakkera HA, Reddy KS , et al. Clinical factors associated with graft fibrosis in kidney-transplant recipients on steroid-avoidance immunosuppression. Clin Transplant 2008; 22 (3) 309-315
  • 32 Heilman RL, Devarapalli Y, Chakkera HA , et al. Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients. Am J Transplant 2010; 10 (3) 563-570
  • 33 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-
  • Immunosuppression Use for Induction by Discharge Regimen. 2004 to 2008 Recipients with Kidney Transplants. (2009). SRTR Database. Retrieved from http://optn.transplant.hrsa.gov/ar2009/506b_ki.htm
  • 35 Dantal J, Berthoux F, Moal MC , et al; RAD A2420 Study Group. Efficacy and safety of de novo or early everolimus with low cyclosporine in deceased-donor kidney transplant recipients at specified risk of delayed graft function: 12-month results of a randomized, multicenter trial. Transpl Int 2010; 23 (11) 1084-1093 10.1111/j.1432-2277.2010.01094.x
  • 36 Devauchelle B, Badet L, Lengelé B , et al. First human face allograft: early report. Lancet 2006; 368 (9531) 203-209
  • 37 Lantieri L, Meningaud JP, Grimbert P , et al. Repair of the lower and middle parts of the face by composite tissue allotransplantation in a patient with massive plexiform neurofibroma: a 1-year follow-up study. Lancet 2008; 372 (9639) 639-645
  • 38 Guo S, Han Y, Zhang X , et al. Human facial allotransplantation: a 2-year follow-up study. Lancet 2008; 372 (9639) 631-638
  • 39 Siemionow M, Papay F, Alam D , et al. Near-total human face transplantation for a severely disfigured patient in the USA. Lancet 2009; 374 (9685) 203-209
  • 40 Pomahac B, Pribaz J, Eriksson E , et al. Restoration of facial form and function after severe disfigurement from burn injury by a composite facial allograft. Am J Transplant 2011; 11 (2) 386-393
  • 41 Mathew JM, Garcia-Morales R, Fuller L , et al. Donor bone marrow-derived chimeric cells present in renal transplant recipients infused with donor marrow. I. Potent regulators of recipient antidonor immune responses. Transplantation 2000; 70 (12) 1675-1682
  • 42 Sheil AG, Moseley RV, Murray JE. Differential skin and renal homograft survival in dogs on immunosuppressive therapy. Surg Forum 1964; 15: 166-168
  • 43 Lee WP, Yaremchuk MJ, Pan YC, Randolph MA, Tan CM, Weiland AJ. Relative antigenicity of components of a vascularized limb allograft. Plast Reconstr Surg 1991; 87 (3) 401-411
  • 44 Kuhr CS, Yunusov M, Sale G, Loretz C, Storb R. Long-term tolerance to kidney allografts in a preclinical canine model. Transplantation 2007; 84 (4) 545-547
  • 45 Dubernard JM, Lengelé B, Morelon E , et al. Outcomes 18 months after the first human partial face transplantation. N Engl J Med 2007; 357 (24) 2451-2460
  • 46 Pellé G, Xu Y, Khoury N, Mougenot B, Rondeau E. Thrombotic microangiopathy in marginal kidneys after sirolimus use. Am J Kidney Dis 2005; 46 (6) 1124-1128
  • 47 Moren M, Testelin S, Petruzzo P , et al. New Partial Face Allograft Transplantation: Report on First Six Months [Abstract]. American Society for Reconstructive Transplant (ASRT). Chicago, IL; Nov 2010.
  • 48 Petruzzo P, Lanzetta M, Dubernard JM , et al. The International Registry on Hand and Composite Tissue Transplantation. Transplantation 2010; 90 (12) 1590-1594
  • 49 Jones JW, Gruber SA, Barker JH, Breidenbach WC. Louisville Hand Transplant Team. Successful hand transplantation. One-year follow-up. N Engl J Med 2000; 343 (7) 468-473
  • 50 Breidenbach WC, Gonzales NR, Kaufman CL, Klapheke M, Tobin GR, Gorantla VS. Outcomes of the first 2 American hand transplants at 8 and 6 years posttransplant. J Hand Surg Am 2008; 33 (7) 1039-1047
  • 51 Ravindra KV, Buell JF, Kaufman CL , et al. Hand transplantation in the United States: experience with 3 patients. Surgery 2008; 144 (4) 638-643 discussion 643–644
  • 52 Dubernard JM, Owen E, Herzberg G , et al. Human hand allograft: report on first 6 months. Lancet 1999; 353 (9161) 1315-1320
  • 53 Petruzzo P, Revillard JP, Kanitakis J , et al. First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. Clin Transplant 2003; 17 (5) 455-460
  • 54 Dubernard JM, Petruzzo P, Lanzetta M , et al. Functional results of the first human double-hand transplantation. Ann Surg 2003; 238 (1) 128-136
  • 55 Petruzzo P, Badet L, Gazarian A , et al. Bilateral hand transplantation: six years after the first case. Am J Transplant 2006; 6 (7) 1718-1724
  • 56 Jabłecki J, Kaczmarzyk L, Patrzałek D , et al. First Polish Hand Allograft – 6-month report. Pol Przegl Chir 2007; 79 (3) 232-238
  • 57 Jablecki J, Kaczmarzyk L, Patrzałek D, Domanasiewicz A, Boratyńska Z. First Polish forearm transplantation: report after 17 months. Transplant Proc 2009; 41 (2) 549-553
  • 58 Jablecki J, Kaczmarzyk L, Domanasiewicz A, Chelmonski A, Boratynska M, Patrzalek D. First Polish forearm transplantation - final report (outcome after 4 years). Ann Transplant 2010; 15 (2) 61-67
  • 59 Cavadas PC, Landin L, Ibañez J. Bilateral hand transplantation: result at 20 months. J Hand Surg Eur Vol 2009; 34 (4) 434-443
  • 60 Landin L, Cavadas PC, Garcia-Cosmes P, Thione A, Vera-Sempere F. Perioperative ischemic injury and fibrotic degeneration of muscle in a forearm allograft: functional follow-up at 32 months post transplantation. Ann Plast Surg 2011; 66 (2) 202-209
  • 61 Piza-Katzer H, Ninkovic M, Pechlaner S, Gabl M, Ninkovic M, Hussl H. Double hand transplantation: functional outcome after 18 months. J Hand Surg [Br] 2002; 27 (4) 385-390
  • 62 Schneeberger S, Ninkovic M, Piza-Katzer H , et al. Status 5 years after bilateral hand transplantation. Am J Transplant 2006; 6 (4) 834-841
  • 63 Schneeberger S, Kreczy A, Brandacher G, Steurer W, Margreiter R. Steroid- and ATG-resistant rejection after double forearm transplantation responds to Campath-1H. Am J Transplant 2004; 4 (8) 1372-1374
  • 64 Schneeberger S, Ninkovic M, Gabl M , et al. First forearm transplantation: outcome at 3 years. Am J Transplant 2007; 7 (7) 1753-1762
  • 65 Schneeberger S, Gorantla VS, van Riet RP , et al. Atypical acute rejection after hand transplantation. Am J Transplant 2008; 8 (3) 688-696
  • 66 Brandacher G, Ninkovic M, Piza-Katzer H , et al. The Innsbruck hand transplant program: update at 8 years after the first transplant. Transplant Proc 2009; 41 (2) 491-494
  • 67 Petruzzo P, Lanzetta M, Dubernard JM , et al. The international registry on hand and composite tissue transplantation. Transplantation 2008; 86 (4) 487-492
  • 68 Breidenbach WC. The Louisville Experience. American Society for Reconstructive Transplant (ASRT). Chicago, IL; Nov 2010.
  • 69 Landin L, Cavadas PC, Ibañez J, Roger I. Malignant skin tumor in a composite tissue (bilateral hand) allograft recipient. Plast Reconstr Surg 2010; 125 (1) 20e-21e
  • 70 Cavadas PC. The Spanish Experience. International Hand and Composite Tissue Allograft Society (IHCTAS). Atlanta, GA; Mar 2011.
  • 71 Yusen RD, Shearon TH, Qian Y , et al. Lung transplantation in the United States, 1999-2008. Am J Transplant 2010; 10(4 Pt 2): 1047-1068
  • 72 Mazariegos GV, Steffick DE, Horslen S , et al. Intestine transplantation in the United States, 1999-2008. Am J Transplant 2010; 10(4 Pt 2): 1020-1034
  • 73 Foster RD, Fan L, Neipp M , et al. Donor-specific tolerance induction in composite tissue allografts. Am J Surg 1998; 176 (5) 418-421
  • 74 Siemionow MZ, Izycki DM, Zielinski M. Donor-specific tolerance in fully major histocompatibility major histocompatibility complex-mismatched limb allograft transplants under an anti-alphabeta T-cell receptor monoclonal antibody and cyclosporine A protocol. Transplantation 2003; 76 (12) 1662-1668
  • 75 Kuo YR, Huang CW, Goto S , et al. Alloantigen-pulsed host dendritic cells induce T-cell regulation and prolong allograft survival in a rat model of hindlimb allotransplantation. J Surg Res 2009; 153 (2) 317-325
  • 76 Mathes DW, Randolph MA, Solari MG , et al. Split tolerance to a composite tissue allograft in a swine model. Transplantation 2003; 75 (1) 25-31
  • 77 Hettiaratchy S, Melendy E, Randolph MA , et al. Tolerance to composite tissue allografts across a major histocompatibility barrier in miniature swine. Transplantation 2004; 77 (4) 514-521