Immunosuppression protocol

The aim is to reduce the incidence of early acute rejection and to optimise long-term allograft function. Immunosuppression is tailored according to an assessment of the patients’ immunological risk. After transfer back to local units post-transplantation, the local nephrology team adjusts immunosuppression.

There are separate pages on Tacrolimus levels, on Steroid avoidance and withdrawal, and on Long-term immunosuppression.

Assessing immunological risk

We base immunological risk on the presence or absence of donor-specific anti-HLA antibodies (DSA) (more about these tests on Crossmatch page) and other markers associated with increased risk of rejection.

Transplantation will not proceed if CDC crossmatch is positive, except in very unusual and carefully planned circumstances. All positive crossmatch or DSA positive cases should be discussed with the H&I team to determine risk and their assessment on pathogenicity of the antibody.

High risk: positive flow (FACS) crossmatch

DSA measured by solid phase assay

  • Irrespective of number or class of antibody
  • No MFI cut-off stated
  • Current or historic

Standard risk: No DSA present. The following features can form part of immunological risk assessment for example for judging maintenance immunosuppression. However, in the absence of DSA, they should generally not lead to enhanced induction:

  • Previous graft failure due to rejection < 1 year
  • Number of HLA mismatches
  • ‘High’ cRF – this may be an additional risk factor in patients with DSA but not without.
  • Pancreas transplant (see SPK protocol)
Immunosuppressive regime: standard risk

This regimen applies to all first, non-sensitised deceased donor recipients with standard immunological risk.

Note that from September 2018, Edinburgh switched to use the Adoport® formulation of Tacrolimus in place of Prograf®. Formulations of Tacrolimus are not interchangeable and must be prescribed as a specific proprietary product.

The age for reducing the standard MMF dose was also reduced from 65 to 60.

Pre-op
(at admission)
  • Mycophenolate mofetil (MMF) PO 1g
  • Tacrolimus (Adoport) PO 0.05mg/kg
Peri-op
  • Basiliximab IV 20mg
  • Methylprednisolone IV 500mg in theatre;
  • And 500mg 24hrs post-op
Post-op
  • Prednisolone PO 20mg daily (to 5mg at 3 months)
  • MMF PO 1g bd at 10:00 and 22:00 (MMF 500mg twice daily if >60 years)
  • Tacrolimus (Adoport) 0.05mg/kg bd at 10:00 and 22:00
Day 4
  • Basiliximab IV 20mg
Immunosuppressive regime: high risk

It is important to identify patients who are at high immunological risk at the time of listing where possible (for example in living donation), although many cases will only become evident on the day of transplant when DSA testing/crossmatching for the offered organ is performed.

Where possible, and in particular if there are any unusual features, the tailored immunosuppressive regimen should be decided at the time of listing, and a clear plan documented (and justified) in the patient’s notes.

In general, high risk cases, consideration should managed as follows:

  • Induction therapy with a T-cell depleting agent, This is generally with ATG (as per protocol page) although Alemtuzumab (Campath®) SC 30mg may be considered.
  • In these cases, such therapy replaces basiliximab.
  • Monitoring of antibody levels post-operatively where there is a known donor specific antibody, and intervention with plasma exchange and/or IVIg as necessary.
  • Tacrolimus as standard dose with target levels 8-12.
  • Prednisolone and MMF are prescribed as above. Early biopsy of these transplanted kidneys should be carefully considered.
Recipients of Marginal grafts: (as per scoring system below)

Standard immunosuppression, with target trough tacrolimus levels of 5-7mg/dl if patient is standard immunological risk.

If patient is at high immunological risk, immunosuppression should be prescribed according to that protocol.

Scoring system for Marginal donor-risk of DGF
Consider as Marginal Graft if Marginal Tx Score > 1
Donor Age > 60 < 65 = 1
Donor NIDDM/IDDM = 1
Donor Hypertension =1
Donor Vascular Disease =1
Donor Cold Ischaemia > 24 hrs =1
Donor Donation after circulatory death (DCD) = 2
Donor Age > 65 = 2
Donor Graft > 20% Sclerosed Gloms on donor biopsy =2
Live Donor Renal Transplant recipients:

The same protocols apply as for deceased donor transplants. Tacrolimus and MMF are commenced at the time of admission of patients for live donor transplants.

Surveillance biopsy:

This is a biopsy carried out at a fixed time point irrespective of other parameters. Recommended in:

  • High immunological risk patients, particularly those with DSA pre-transplant/positive flow (FACS) crossmatch
  • Previous graft lost to early AR
  • ABO incompatibility
  • Recipient with an episode of early acute rejection
  • Patients with high risk of recurrent disease
  • De novo DSA

The optimal time period whereby results may impact management is within 3-6 months of transplant.

 

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