Saturday, August 11, 2007

Immunosuppression protocol- CPG

41. IMMUNOSUPPRESSION PROTOCOL

41.1 The standard immunosuppression regimen
The standard immunosuppression regimen (adult1,2,3,10,11,12,13,14,15,16 and LRRT in children18) consists of tacrolimus / cyclosporin, mycophenolate mofetil (MMF) and prednisolone. (Level A)

41.1.1 The immunosuppression regimen may be modified in the following situations:
a. Polyclonal4,5/monoclonal antibody6 or anti-ILII antibody7,19,20 can be used as induction immunotherapy when acute tubular necrosis or delayed graft function is anticipated and in highly sensitised recipients. (Level A)
However Anti-IL II antibody has minimal side effects and is easier to use.4
b. In highly sensitised recipients i.e. multiparous female, multiple blood transfusion and previous history of transplant, PRA >20%, cadaveric transplantation in children, tacrolimus may be used instead of cyclosporin,8,9, and/or the use polyclonal5/monoclonal antibody 6 or anti-ILII antibody7,19,20 as induction immunotherapy.

41.2 Immunosuppressive agents
41.2.1 Corticosteroids
a. Hydrocortisone 200 mg IV stat on call to theatre and post-operatively and 8-hourly until patient is tolerating orally
b. IV Methylprednisolone 500 mg at anastomosis for cadaveric renal transplant in addition to the above
c. Hydrocortisone is replaced by prednisolone 20 mg daily when allowed orally
d. Prednisolone is tapered off beginning at 3 months post-transplant, by 2.5 mg per month till the dose of 10 mg daily is reached
e. Prednisolone may be reduced to 5 – 7.5 mg daily in selected patients (e.g. stable recipient with severe steroid toxicity)

41.2.2 Cyclosporin
a. For living related renal transplantation, Neoral 8 mg/kg/day to begin 5 days pre-transplant
b. For cadaveric transplant, dose of Neoral is 10 mg/kg/day given pre transplant
c. Dose of Neoral is adjusted according to trough levels or C2

Trough levels
• Less than 6 months post-transplant: 250-375 ng/ml
• 6 months or more post-transplant: 100-250 ng/ml
C2 levels
• Less than 1 month: 1.7 ug/ml
• 1-2 months: 1.5 ug/ml
• 2-3 months: 1.3 ug/ml
• 4-6 months: 1.1 ug/ml
• 7–12 months: 0.9 ug/ml
• more than 12 months: 0.8 ug/ml

41.2.3 Tacrolimus
a. For living related renal transplantation, tacrolimus 0.2 mg/kg/day to begin 5 days pre-transplant
b. For cadaveric transplant, dose of tacrolimus is 0.3 mg/kg/day given per oral when called to operating theatre.
c. Post-operatively, tacrolimus is given at 0.2 mg/kg/day in divided doses
d. Dose is adjusted according to trough levels:
• Less than 6 months post-transplant: 10-15 ng/ml
• 6 months or more post-transplant: 5-10 ng/ml

41.2.4 Mycophenolate mofetil
a. On call to theatre, mycophenolate mofetil is given 1 g per oral
b. Post-transplant, mycophenolate mofetil is given 1 g twice a day per oral (dose in children 600 mg/m2/dose 12 hourly)
c. Dose is reduced or omitted if total white counts are <> 8 yr
Oral MMF 300 mg/m2/dose stat dose before going to OT
Tacrolimus 0.1 mg/kg/dose b.d.
IV Methyprednisolone 600 mg/m2 BSA just prior to
anastomosis of renal vessels
D1 IV Hydrocortisone 5 mg/kg/dose tds
Oral MMF 300 mg/m2/dose bd
Tacrolimus 0.1 mg/kg/dose b.d.
D2 Prednisolone 60 mg/m2/day b.d. dosing
Oral MMF 300 mg/m2/dose bd
Tacrolimus 0.1 mg/kg/dose b.d.
D4 Repeat IV Basiliximab

41.3.2 Living Related Renal Transplant
D – 5 Oral Cyclosporin 10 mg/kg/day in b.d. dosing or tacrolimus 0.2 mg/kg/day b.d.
Oral MMF 600 mg/m2/dose bd (reduced by 50% if used in combination with tacrolimus)
D0 IV Methyprednisolone 600 mg/m2 BSA prior to anastomosis
of vessels
Oral Cyclosporin 10 mg/kg/day in b.d. dosing or tacrolimus 0.2 mg/kg/day b.d.
Oral MMF 600 mg/m2/dose bd (reduced by 50% if used in combination with tacrolimus)
D1 IV Hydrocortisone 5mg/kg/dose tds
Oral Cyclosporin 10 mg/kg/day in b.d. dosing or tacrolimus 0.2 mg/kg/day b.d.
Oral MMF 600 mg/m2/dose bd (reduced by 50% if used in combination with tacrolimus)
D2 Prednisolone 60 mg/m2/day bd dosing
Oral Cyclosporin 10 mg/kg/day in b.d. dosing or tacrolimus 0.2 mg/kg/day b.d.
Oral MMF 600 mg/m2/dose bd (reduced by 50% if used in combination with tacrolimus)

41.3.3 Guidelines for drug dose tapering in paediatric renal transplant recipients
a. Cyclosporin / tacroloimus – follow adult schedule
b. Prednisolone - start tapering the dose 1 week post-transplant and taper 10 mg/week till 10 – 12.5 mg daily if renal function is stable and cyclosporin / tacrolimus is within the desired range.




References
1. The Canadian Multicentre Transplant Study Group. A randomised clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med 1983; 309: 809-815
2. The Canadian Multicentre Transplant Study Group. A randomised clinical trial of cyclosporine in cadaveric renal transplantation.Analysis at three years. N Engl J Med 1986; 314: 1219-1225
3. European Multicentre Trial Group. Cyclosporin in cadaveric renal transplantation: one-year follow-up of a multicentre trial. Lancet 1983; 986-989
4. Slakey D, Johnson C, Callaluce R et al. A prospective randomised comparison of quadruple versus triple treatment for the first cadaver transplant with immediate graft function. Transplantation 1996; 56: 827-831
5. Wechter W, Brodie J, Morrell R et al. Antithymocyte globulin (ATGAM) in renal allograft recipients. Transplantation 1979; 28: 294-302.
6. Abramowicz D, Goldman M, De Pauw L et al. The long term effect of prophylactic OKT3 monoclonal antibody in cadaveric kidney transplantation – a single centre, prospective ,randomised study. Transplantation 1992; 54: 433-437
7. Nashan B, Moore R, Amlot P et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet 1997; 350: 1193-1198
8. European Tacrolimus Multicentre Renal Study Group. Multicentre randomised trial comparing tacrolimus and cyclosporin in prevention of renal allograft rejection. Transplantation 1997; 64: 436-443
9. Johnson C, Ahsan N, Gonwa T et al. Randomised trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporin (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 2000; 69: 834-841
10. Shapiro R, Jordan M, Scantlebury V et al. A prospective randomised trial of tacrolimus/prednisolone versus tacrolimus/prednisolone/mycophenolate mofetil in randomised transplant recipients. Transplantation 1999; 67: 411-415
11. Halloran P, Mathew T, Tomlanovich S et al. Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Study Groups. Transplantation 1997; 63(1): 39-47
12. Tricontinental Mycophenolate Mofetil Renal Transplant Study Group. A blinded randomised clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61: 1029-1037
13. Tricontinental Mycophenolate Mofetil Renal Transplant Study Group. A blinded long-term randomised multicentre study of mycophenolate mofetil in cadaveric renal transplantation: results at 3 years. Transplantation 1998; 65: 1450-1454
14. European Mycophenolate Mofetil Multicentre Cooperative Study Group. Placebo control study of Mycophenolate Mofetil combined with cyclosporin and steroid for prevention of acute rejection. Lancet 1995; 345: 1321-1325
15. European Mycophenolate Mofetil Multicentre Cooperative Study Group. Mycophenolate Mofetil in renal transplant: 3-year results for placebo controlled trial. Transplantation. 1999; 68: 391-396
16. US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate Mofetil in cadaveric renal transplant. Am J Kidney Dis 1999; 34: 296-303
17. Michael HJ, Francos GC, Burke JF et al. A comparison of the effect of cyclosporin versus antilymphocyte globulin on delayed graft function in cadaveric renal transplant recipients. Transplantation 1999; 48: 805-808
18. Renal transplantation, chronic dialysis and chronic renal insufficiency in children and adolescents. The 1995 annual report of the North Paediatric Renal Transplant Cooperative Study. Paed Nephrol 1997; 11: 49-64
19. Kahan B. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, achimeric anti-chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Group Study. Transplantation 1999; 67(2): 276-84
20. Meier-Kriesche et al. The effect of daclizumab in high risk renal transplant population. Clin Transplant 2000; 14(5): 509-13

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