Antibody-mediated rejection (AMR)
Following a diagnosis of potential AMR discussion must take place between pathologist + H&I + relevant clinicians, and this team will make a decision as to whether to follow this protocol or to deviate from this (for example if evidence of cellular rejection the use of ATG may be advocated).
Management of AMR (in HLA & ABO compatible transplants)
- Methylprednisolone 500mg IV given every day for 3 days
ii. PLASMA EXCHANGE
- This should be started no sooner than 24 hours after a renal biopsy
- 5 alternate day exchanges
- Discuss with BTS regarding replacement fluid (albumin vs. FFP)
- Monitor for hypocalcaemia, bleeding and infection
iii. IMMUNOGLOBULIN (iv Ig)
- 5 doses of 100mg/kg given at the end of each plasma exchange
- IV Ig is made up by Pharmacy. An immunoglobulin request form will need to be completed.
- Prescribe as Octagam, start the infusion at 0.6ml/kg/h for first 30mins.
- Then increase rate to 1.2ml/kg/hr for the remainder of the infusion.
Observation during infusion
Usual observations as for patients receiving blood products apply.
Monitor temperature, pulse, BP every 15mins for first hour, then hourly thereafter.
IV. OTHER IMMUNOSUPPRESSION
This should be continued as pre standard protocol (MMF, tacrolimus)
There should be monitoring of donor specific antibody level and renal biopsy at the end of this 10-day protocol to assess treatment efficacy.
Patients requiring steroid sparing or avoidance protocols should be selected, for example, for patients with a history of steroid-induced psychosis prior to listing, and counseled that they will be at increased risk of rejection.
Steroid-sparing protocol (Based on Royal Free London)
- Basiliximab, tacrolimus and MMF as standard.
- 500mg methylprednisolone at day 0 followed methylprednisolone 40mg od for 4 days converting to 20mg prednisolone thereafter. Steroids are then stopped completely at day 10.
If there was a history of steroid exacerbated psychosis
- Basiliximab, MMF 1g bd as standard
- Ensure tacrolimus level of 12 early on.
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.
STRONGLY RECOMMEND CONSIDERATION OF RENAL BIOPSY REGARDLESS OF CREATININE IF CONSIDERING STEROID WITHDRAWAL, ALTERATION/SWITCH IN IMMUNOSUPPRESSION AND CREEPING CREATININE
Recommended Steroid Tapering
Week 1 Prednisolone 20mg
Week 4 Prednisolone 15mg
Week 8 Prednisolone 10mg
Week 12 Prednisolone 5mg
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.
In sensitised and kidney-pancreas transplant patients, reduction in MMF dose should be avoided given risk of rejection.
Proposed options for long-term Immunosuppression:
Low risk recipient consider:
- Steroid withdrawal
- Replacing MMF with Azathioprine
- Steroid withdrawal
- Low CNI level
(if patient is pregnant the following is mandatory):
- Replace MMF with Azathioprine prior to conception or as soon as possible after conception in the event that pregnancy was unplanned.
- Consider pre-pregnancy biopsy along with DSA screen.