The aim is to reduce the incidence of early acute rejection and to optimise long-term allograft function. As patients return to their local Renal Units post-transplantation, it is the responsibility of the local nephrology team to tailor immunosuppression in the long-term. Options for maintenance therapy are outlined below. At the outset, it is important to access patients' immunological risk, with the aim of tailoring immunosuppression accordingly.
We base immunologial risk on the presence or absence of donor-specific anti-HLA antibodies (DSA), as measured by solid phase assays or conventional crossmatching (Flow/FACS). Transplantation will not proceed if CDC crossmatch is positive. 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 anti-body.
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: all renal transplants
I. Standard Regimen
This regimen applies to all first, non-sensitised deceased donor recipients with standard immunological risk.
|Pre-op (at admission)||
II. High immunological 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.
A tailored immunosuppressive regimen should be decided at the time of listing were possible, and a clear plan documented 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.
It is likely that the transplant unit may switch to using Tacrolimus (Adoport®) in the near future. Adoport® is a biosimilar with eqquivalent clinical efficacy and adverse event profile. It should be used at the same dose that is stipulated for Prograf®.
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.
This is a biopsy carried out at a fixed time point irrespective of other parameters.
This is 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.
Next page: Tacrolimus levels