Simultaneous islet and kidney transplantation in seven patients with type 1 diabetes and end-stage renal disease using a glucocorticoid-free immunosuppressive regimen with alemtuzumab induction

Jianming Tan, Shunliang Yang, Jinquan Cai, Junqi Guo, Lianghu Huang, Zhixian Wu, Jin Chen, Lianming Liao, Jianming Tan, Shunliang Yang, Jinquan Cai, Junqi Guo, Lianghu Huang, Zhixian Wu, Jin Chen, Lianming Liao

Abstract

Objective: The aim of this study was to evaluate the efficiency and safety of simultaneous islet and kidney transplantation in patients with type 1 diabetes and end-stage renal disease using a glucocorticoid-free immunosuppressive regimen with alemtuzumab induction.

Research design and methods: Seven patients with type 1 diabetes and end-stage renal failure were transplanted with allogenic islets and kidneys procured from brain-dead donors. To prevent organ rejection, patients received alemtuzumab for induction immunosuppression, followed by sirolimus and tacrolimus. No glucocorticoids were given at any time.

Results: The median duration of follow-up was 18.3 months (range 13-31). Kidney survival was 100%. Four patients became insulin independent at 1 year. The other three reduced insulin use to less than 25% of the amount required before transplantation. Serum C-peptide levels were significantly greater posttransplant in all patients, indicating continued islet function. No major procedure-related complications were observed.

Conclusions: Our results demonstrate that a steroid-free immunosuppressive regimen consisting of alemtuzumab, sirolimus, and tacrolimus is feasible for simultaneous islet and kidney transplantation. The question of whether this induction regimen is superior to more standard induction deserves large studies.

Trial registration: ClinicalTrials.gov NCT00692562.

Figures

FIG. 1.
FIG. 1.
Metabolic control and islet graft function after transplantation. Values of A1C data (A) show improvement in all patients after islet transplantation. Results of premeal (B) and postmeal (C) C-peptide values demonstrate the benefits of the transplant on metabolic control during the follow-up period.
FIG. 2.
FIG. 2.
Renal function of the recipient. Serum concentrations of creatinine after transplantation (□) are significantly lower than those before transplantation (▪) (P < 0.01). Glomerular filtration rate increases to near normal posttransplant.

References

    1. Diabetes Control and Complication Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986, 1993
    1. Scharp DW, Lacy PE, Santiago JV, McCullough CS, Weide LG, Falqui L, Marchetti P, Gingerich RL, Jaffe AS, Cryer PE, Anderson CB, Flye MW: Insulin independence after islet transplantation into type I diabetic patient. Diabetes 39:515–518, 1990
    1. Socci C, Falqui L, Davalli AM, Ricordi C, Braghi S, Bertuzzi F, Maffi P, Secchi A, Gavazzi F, Freschi M: Fresh human islet transplantation to replace pancreatic endocrine function in type 1 diabetic patients. Acta Diabetol 28:151–157, 1991
    1. Warnock GL, Kneteman NM, Ryan EA, Rabinovitch A, Rajotte RV: Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35:89–95, 1992
    1. European IDDM Policy Group: Consensus guidelines for the management of insulin-dependent (type 1) diabetes. Diabetic Med 10:990–1005, 1993
    1. American Diabetes Association: Standards of medical care for patients with diabetes mellitus. Diabetes Care 17:616–623, 1994
    1. Robertson RP: Consequences on β-cell function and reserve after long-term pancreas transplantation. Diabetes 53:633–644, 2004
    1. Israni AK, Feldman HI, Propert KJ, Leonard M, Mange KC: Impact of simultaneous kidney-pancreas transplant and timing of transplant on kidney allograft survival. Am J Transplant 5:374–382, 2005
    1. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med343:230–238, 2003
    1. Edmond A. Ryan, Breay W. Paty, Peter A. Senior, David Bigam, Eman Alfadhli, Norman M. Kneteman, Jonathan R.T. Lakey, and AMJames Shapiro: Five-year follow-up after clinical islet transplantation. Diabetes 54:2060–2069, 2005
    1. Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR: Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561, 2002
    1. Magliocca JF, Knechtle SJ: The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transpl Int 19:705–714, 2006
    1. Gruessner RW, Kandaswamy R, Humar A, Gruessner AC, Sutherland DE: Calcineurin inhibitor- and steroid-free immunosuppression in pancreas-kidney and solitary pancreas transplantation. Transplantation 79:1184–1189, 2005. May 15
    1. Kaufman DB, Leventhal JR, Gallon LG, Parker MA: Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction: long-term results. Am J Transplant 6:331–339, 2006
    1. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW: Automated method for isolation of human pancreatic islets. Diabetes 37:413–420, 1988
    1. Tyden G, Bolinder J, Solders G, Brattstrom C, Tibell A, Groth CG: Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation. Transplantation 5:645–648, 1999
    1. Smets YF, Westendorp RG, van der Pijl JW, de Charro FT, Ringers J, de Fijter JW, Lemkes HH: Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure. Lancet 353:1915–1919, 1999
    1. Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, Kandaswamy R, Mauer SM, Kennedy WR, Goetz FC, Robertson RP, Gruessner AC, Najarian JS: Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 233:463–501, 2001
    1. Augustine JJ, Hricik DE: Steroid sparing in kidney transplantation: changing paradigms, improving outcomes, and remaining questions. Clin J Am Soc Nephrol 1:1080–1089, 2006
    1. Bertuzzi F, Grohovaz F, Maffi P, Caumo A, Aldrighetti L, Nano R, Hengster P, Calori G, Di Carlo V, Bonifacio E, Secchi A: Successful transplantation of human islets in recipients bearing a kidney graft. Diabetologia 45:77–84, 2002
    1. Waldmann TA, O'Shea J: The use of antibodies against the IL-2 receptor in transplantation. Curr Opin Immunol 10:507–512, 1998
    1. Bruce DS, Sollinger HW, Humar A, Sutherland DE, Light JA, Kaufman DB, Alloway RR, Lo A, Stratta RJ: Multicenter survey of daclizumab induction in simultaneous kidney-pancreas transplant recipients. Transplantation 72:1637–1643, 2001
    1. Lehmann R, Weber M, Berthold P, Züllig R, Pfammatter T, Moritz W, Mädler K, Donath M, Ambühl P, Demartines N, Clavien And PA, Andreia Spinas G: Successful simultaneous islet-kidney transplantation using a steroid-free immunosuppression: two-year follow-up. Am J Transplant 4:1117–23, 2004
    1. Toso C, Baertschiger R, Morel P, Bosco D, Armanet M, Wojtusciszyn A, Badet L, Philippe J, Becker CD, Hadaya K, Majno P, Buhler L, Berney T; the GRAGIL group: Sequential kidney/islet transplantation: efficacy and safety assessment of a steroid-free immunosuppression protocol. Am J Transplant. 6:1049–1058, 2006
    1. Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, Neylan J, Wilkinson A, Ekberg H, Gaston R, Backman L, Burdick J the Daclizumab Triple Therapy Study Group: Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 338:161–165, 1998
    1. Morris Peter J, Russell Neil K: Alemtuzumab (Campath-1H): A systematic review in organ transplantation. Transplantation. 81:1361–1367, May 27, 2006
    1. Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roohipour R, Carreno MR, Roth D, Ruiz P, Kupin W, Rosen A, Esquenazi V, Tzakis AG, Miller J: The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation 78:426–433, 2004
    1. Flechner SM, Friend PJ, Brockmann J, Ismail HR, Zilvetti M, Goldfarb D, Modlin C, Mastroianni B, Savas K, Devaney A, Simmonds M, Cook DJ: Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression. Am J Transplant 5:3009–3014, 2005
    1. Vathsala A, Ona ET, Tan SY, Suresh S, Lou HX, Casasola CB, Wong HC, Machin D, Chiang GS, Danguilan RA, Calne R: Randomized trial of Alemtuzumab for prevention of graft rejection and preservation of renal function after kidney transplantation. Transplantation 80:765–774, 2005
    1. Kaufman DB, Leventhal JR, Axelrod D, Gallon LG, Parker MA, Stuart FP: Alemtuzumab induction and prednisone-free maintenance immunotherapy in kidney transplantation: comparison with basiliximab induction–long-term results. Am J Transplant 5:2539–2548, 2005

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe