EdRen - Edinburgh Royal Infirmary Renal Unit

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IMMUNOSUPPRESSION PROTOCOL - OCTOBER 2009

EDINBURGH, INVERNESS, ABERDEEN, DUNDEE, FIFE.

Introduction

The regimens outlined below have been developed with the collaborative efforts of all Renal Units in the East of Scotland. The main aims of these protocols are to reduce the incidence of early acute rejection and to optimise allograft function.

As patients return to their local Renal Units post-transplantation, it will be the responsibility of the local nephrology teams to tailor immunosuppression in the long-term. The options for maintenance therapy will be outlined below.

Cadaveric Heart-beating Renal Transplant

(1) Standard Regimen

This regimen applies to all first, unsensitised cadaveric graft recipients with no DR-mismatch.

(2) Intermediate risk patients

This group includes simultaneous kidney/pancreas transplants, previous transplant, sensitised patients, FACS positive crossmatch, any DR-mismatch, non-favourable match, black race. The only difference here is the target trough level of tacrolimus is higher.

Pre-op (at admission)	MMF Tacrolimus	1g 0.05mg/kg
Peri-op	Simulect Methylprednisolone	20mg 500mg in theatre; 500mg at 24hrs post-op
Post-op	Prednisolone MMF Tacrolimus	20mg daily (reducing to 5mg at 3 months) 1g bd at 08:00 and 20:00 hrs 0.05mg/kg bd at 10:00 and 22:00 hr
1. Standard regimen 2. Intermediate risk patients		target trough level 5-10 target trough level 10-14 in first 3 months target trough level 5-10 after 3 months
Day 4	Simulect	20mg

Live Donor Renal Transplant

All live donor transplants, including those from unrelated donor, will receive the standard regimen as above BUT with pre-treatment starting 2 days pre-transplant. The tacrolimus dosage for pre-treatment will be half of the standard dose post-transplant.

Pre-op
(start 2 days pre-Tx)

Prednisolone
MMF
Tacrolimus

20mg
1g bd at 08:00 and 20:00 hrs
0.025mg/kg bd at 10:00 and 22:00 hrs

Then as for cadaveric heart-beating donor (as above)

Non-Heart Beating Cadaveric Renal Transplant

The differences here are that patients do not get tacrolimus pre-operatively, and the target trough level is lower than for heart-beating donors.

Pre-op (At admisson)	MMF	1g Note: No pre-op tacrolimus given
Peri-op	Simulect Methylpredinsolone	20mg 500mg in theatre; 500mg at 24hrs post-op
Post-op	Prednisolone MMF Tacrolimus	20mg daily (reducing to 5mg at 3 months) 1g bd at 08:00 and 20:00 hrs 0.05mg/kg bd at 10:00 and 22:00 hrs
	target trough level 5 - 7
Day 4	Simulect	20mg

Note: if a patient has a kidney transplant from a non-heart beating donor, and is considered to be at increased risk of rejection, the consultant clinicians responsible for the patient should alter the target trough level of tacrolimus at their discretion, and depending on the clinical scenario.

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Recommended Steroid Tapering

Week 1    Prednisolone 20mg
Week 4    Prednisolone 15mg
Week 8    Prednisolone 10mg
Week 12 Prednisolone 5mg

Mycophenolate Mofetil

Maintaining the dosage of MMF is essential to allow minimisation of CNI dosage. However, side-effects may occur.

Gastrointestinal side-effects are common. Consider:

An alternative cause of diarrhoea and exclude infection
A small dose reduction and/or splitting dose to tds or qds
Switching to Myfortic 720mg bd

Leucopenia may occur. Exclude CMV infection. Consider:

A small dose reduction and monitor white cell count.

CMV Prophylaxis

All patients receiving a kidney and/or pancreas transplant except CMV negative recipients of CMV negative grafts should receive prophylaxis with Valganciclovir (dosing according to eGFR)

Duration of prophylaxis should extend to 6 months (180 days)

Treatment of Acute Rejection

Acute rejection should be confirmed with percutaneous transplant biopsy.
Treatment: Methylprednisolone 500mg IV daily for 3 consecutive days.
Review maintenance regimen– tacrolimus trough level should be increased to 7-10.
Steroid-resistant acute rejection – Anti-thymocyte globulin (ATG) should be considered.

Long-term Immunosuppression

The immunosuppressive regimen will be reviewed at 6 months post-transplant by the nephrologist responsible for the care of the patient. Patients will be informed prior to transplantation that their immunosuppressive regimen will be reassessed at this stage and may involve a change of medication, change in dosage of medication or continuation of the initiating regimen. This decision must be clearly documented.

It will be the choice of individual Renal Units to decide if they wish to pursue steroid withdrawal or CNI dose minimisation. This decision may be taken on an individual patient basis.

Proposed options for long-term Immunosuppression:

Low risk recipient consider:

Steroid withdrawal
Replacing MMF with Azathioprine

Creeping creatinine consider:

Lower CNI level

NODAT consider:

Steroid withdrawal
Low CNI level

Pregnancy (this is mandatory):

Replace MMF with Azathioprine prior to conception or as soon as possible after conception in the event that pregnancy was unplanned.

Data Collection

As transplant follow-up will be devolved to regional centres, it is essential to collection transplant follow-up data for accurate assessment of this revised immunosuppression protocol. Each unit should nominate a lead clinician to coordinate data collection and liaise with their respective transplant coordinator.

Each Unit should collect data on:

Number of patients transplanted each year
Acute rejection episodes – timing post-transplant, severity (Banff grade), treatment (including use of antibody)
Immunosuppressive regimen at 6 and 12 months
Serum creatinine at 6 and 12 months
eGFR (MDRD) at 6 and 12 months
Infections during first 12 months (CMV, BK virus, other)
Malignancy during first 12 months (non-skin)
New-onset diabetes after transplantation (NODAT)
Graft survival at 12 months
Patient survival at 12 months

It is planned that Scottish Renal Registry data collection should be used to facilitate this and that data fields should be set up to enable this to happen.

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