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Kidney Transplantation

BTS/RA Living Donor Kidney Transplantation Guidelines Fourth Edition Mar 2018. RA Clinical Practice Guidelines Post-Operative Care in the Kidney Transplant Recipient. Last revised Feb 2017.

Pre-Transplantation Guidelines

  1. Early Screening - identify compatibility
    • ABO blood group typing
    • HLA typing (donor and recipient)
    • Virtual crossmatch (using latest HLA antibody profile)
  2. Full donor workup
    • Medical, surgical and psychosocial assessments
  3. Structured immunological monitoring
    • Recipient HLA antibody screening 
    • Direct crossmatch performed

Compatible ABO blood group is required.

HLA compatibility is assessed using a mismatch grading system:
  • 0.0.0 (perfect match): no mismatch at the 3 key loci HLA-A, -B, and -DR
  • 2.2.2 (full mismatch): 2 mismatches at all 3 key loci HLA-A, -B, and -DR (6 mismatches in total)

In short, 0.0.0 (perfect HLA match) is preferred and has the best prognosis.

 

Sibling donors have a 25% chance of being a perfect match (0.0.0).

Note that there are 2 copies of each HLA locus, each locus can have 0, 1, or 2 mismatches, with 27 possible combinations. The maximum number of total mismatches is 6.

1st line option for ALL incompatible donor-recipient pairs: consider for UKLKSS (UK Live Kidney Sharing Scheme)

If no suitable match in UKLKSS: consider AIT (antibody incompatible transplantation) in an experienced centre
 

Can only proceed in centres with ≥5 ABOi transplants / year

Pre-transplantation management:

  • Titration of isohaemagglutinins (anti-A or anti-B)
  • Desensitisation (plasmapheresis or immunoadsorption)
  • Pre-treatment with rituximab

Pre-transplantation management:
  • Pre-treatment with rituximab + IVIGIntravenous immunoglobulin +/- antithymocyte globulin
  • Desensitisation (plasmapheresis or immunoadsorption)

  • Blood tests: FBC, U&Es, LFTs, fasting glucose, lipid profile, coagulation profile
  • Infection screening: HIV, HBV, HCV, CMV/EVC IgG, HTLV-1/2, syphilis, HEV (if at risk), TB 
  • Urinalysis 

  • GFR measurement: Isotope (mGFR) or iohexol clearance if eGFR < 90
  • Renal anatomy: CT-angiography or MRA
  • Cardiac risk: ECG +/- ECHO, stress test if cardiovascular risk present
  • Bone density: DEXA if osteopenia suspected

  • Hypertension, obesity (BMI >30), diabetes
  • Malignancy risk or family history of renal disease
  • Donors with prior pregnancy, liver or haematological conditions

  • HLA antibody screening every 3 months
  • Detect donor-specific antibodies
  • Re-screen after any sensitising event (e.g. transfusion, pregnancy, change in immunosuppression)
 
  • Perform direct crossmatching using recipient serum within 14 days of transplant

 

+ve Direct crossmatch is a contraindication to transplantation unless desensitisation is used.

Post-Transplantation Guidelines

Induction therapy should be started before or at the time of renal transplantation.

All patients should receive a biological induction agent:
  • Low immunological risk: generally IL2-RAInterleukin-2 receptor antagonist (e.g. basiliximab)
  • High immunological risk: consider for T-cell depleting antibodies (e.g. antithymocyte globulin)
 

Also start the calcineurin inhibitor (tacrolimus / ciclosporin) at the time of transplant, but it is part of maintenance, not induction.

1st line triple therapy in low / medium immunological risk:
  • Calcineurin inhibitor - tacrolimus preferred over ciclosporin
  • Anti-proliferative agent - mycophenolic acid-based (MPA) drugs preferred 
  • +/- Corticosteroids

 

Calcineurin inhibitor (tacrolimus / ciclosporin) should be started at time of transplantation.

Calcineurin inhibitors should NOT be withdrawn.


2nd line options:
  • Calcineurin inhibitor alternatives (if tacrolimus not appropriate)
    • Ciclosporin (calcineurin inhibitor)
    • Sirolimus (mTOR inhibitor)
    • Everolimus (mTOR inhibitor)
    • Belatacept (CTLA4-Ig inhibitor)
    • Modified-release tacrolimus (if peak dose side effects are problematic)
 
  • Anti-proliferative agent alternatives (if MPA drugs not appropriate)
    • Azathioprine - in fertile patients who are unwilling to use reliable contraception
 

Patient at risk of developing post-transplant diabetes mellitus is a recognised adverse effect of tacrolimus and a common reason to avoid tacrolimus

Long-term monitoring of the following is recommended:
  • Tacrolimus - trough level
  • Ciclosporin - trough level or 2-hour post-dose
  • Sirolimus - trough level

BTS guidelines state that the utility of monitoring MPA drugs is uncertain.

To diagnose acute rejection:
  • Renal biopsy with  C4d and SV40 staining (ideally before starting treatment unless this would cause significant delay or risk)
  • Serum sample at time of biopsy to check for HLA-specific antibodies

There are 2 types of acute rejections:
 
  ACR (acute cellular rejection) AMR (antibody-mediated rejection)
Pathophysiology T-cell (cytotoxic T cells) mediated immune response Donor-specific antibodies against HLA or other antigens
Biopsy finding Prominent tubulitis and interstitial infiltrate Usually mild or absent
Biopsy C4d staining Negative Positive in peritubular capillaries
Serum sample  Usually absent Present in most cases

Hyperacute rejection is very rare and involves pre-formed antibodies against HLA or antigens of the donor.

BTS guidelines do not specify the management of hyperacute rejection as the pre-transplant screening practices and protocols effectively prevents it.

If hyperacute rejection happens, management involves immediate removal of the graft.

1st line: high-dose IV corticosteroids + add or restart steroids into maintenance therapy

If refractory or aggressive vascular rejection: consider lymphocyte-depleting agents

Treat with one or more of the following:

  • Steroids
  • Plasma exchange
  • IVIGIntravenous immunoglobulin
  • Anti-CD20 antibody
  • Lymphocyte-depleting antibody
  • Bortezomib

MPA drugs are effective in preventing antibody-mediated rejection and should be part of the maintenance therapy:
  • If patient is on azathioprine → switch to MPA drugs
  • If patient is already on MPA drugs  → maximise the existing dose

Screen for chronic allograft injury by monitoring renal function at each clinic visit by:
  • Serum creatinine
  • Urine dipstick and ACRAlbumin:creatinine ratio / PCRProtein:creatinine ratio
    • Look for new-onset proteinuria

Features suggestive of chronic allograft injury include:

  • Unexplained elevation of creatinine beyond baseline
  • Sustained new onset proteinuria (ACR >35 mg/mmol or PCR >50 mg/mmol)
  • Expected renal function not achieved within 4-8 weeks

In these patients, a renal biopsy is indicated.
 
To diagnose chronic allograft injury:
  • Renal biopsy with  C4d + SV40 staining - gold standard
  • Serum sample at time of biopsy to check for HLA-specific antibodies

  • If there is histological evidence of calcineurin inhibitor toxicity or non-specific interstitial fibrosis and tubular atrophy → stop calcineurin inhibitors (tacrolimus / ciclosporin)
  • If there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection) → intensify immunosuppression
  • Manage similarly to other patients with CKD

The BTS guideline outlines a broad range of recommendations to support the long-term health and graft survival of kidney transplant recipients. Key management priorities are summarised below.
 

  • Strict hypertension control
  • Annual fasting lipid profile
  • Screen regularly for post-transplant diabetes mellitus

Also offer general lifestyle recommendations like any other:
  • Encourage a healthy diet
  • Maintain BMI ≤25 kg/m2
  • Promote regular physical activity
  • Advise on smoking cessation and moderate alcohol intake 
  • Avoid unsupervised over-the-counter medications

Immunosuppression increases the risk of non-melanoma skin cancer, especially squamous cell carcinoma:
  • Biannual skin checks for the first 5 years post-transplant, then annually
  • Advise on sun protection measures

Patients should:
  • Avoid live attenuated vaccines
  • Otherwise, receive inactivated vaccines per standard schedules
  • Annual influenza vaccination is recommended

The following extra infection prophylaxis is recommended
  • VZV vaccination in IgG-negative patients prior to transplantation

  • CMVCytomegalovirus prophylaxis for 3-6 months post-transplant or until immunosuppression is reduced to maintenance levels
  • PJP prophylaxis with co-trimoxazole for 3-6 months post-transplant
 
  • Monitor high-risk patients for EBVEpstein-Barr virus viral load post-transplant
  • Screen for BK virus in cases of unexplained renal dysfunction and confirm diagnosis with renal biopsy + SV40 staining

Female patients:
  • Discontinue MPA drugs prior to conception and replace with azathioprine
  • Wait at least 1 year post-transplant with stable graft function before attempting conception
  • Consider low-dose aspirin to reduce pre-eclampsia risk

Male patients:
  • Mycophenolate mofetil and enteric-coated mycophenolate sodium (Myfortic®) have theoretical teratogenic potential 
  • mTOR inhibitors may reduce sperm count 

References

Author: Adams Lau
Reviewer:
Last edited: 13/05/25