Key Facts

Renal transplantation transforms the lives of patients with ESRD. The NHS Blood and Transplant (NHSBT) organ allocation system uses a national algorithm based on HLA matching, waiting time, and sensitisation.

Epidemiology

• ~3,000 kidney transplants/year in the UK
• Median waiting time: ~2-3 years for deceased donor
• Living donor transplants: ~1,000/year (increasing)
• ~5,000 patients on waiting list at any time
• 5-year graft survival: living donor 90%, deceased donor 85%

Types of Donor

• Living donor: related or unrelated (altruistic); best outcomes; planned surgery
• Deceased donor – donation after brain death (DBD): heart-beating donor; good outcomes
• Deceased donor – donation after circulatory death (DCD): increasing proportion; slightly higher delayed graft function
• ABO-incompatible and HLA-incompatible: desensitisation protocols available
• Paired/pooled exchange: living donor swap schemes

Immunology

• HLA matching: HLA-A, -B, -DR most important; better matching = longer graft survival
• Crossmatch: pre-transplant; detects pre-formed donor-specific antibodies (DSA)
  • Positive crossmatch = contraindication to transplant (hyperacute rejection)
• Panel reactive antibodies (PRA): measures sensitisation level
• Sensitisation sources: previous transplants, blood transfusions, pregnancy

Post-Transplant Complications (by Timing)

Immediate (0-7 days):

• Hyperacute rejection: minutes-hours; pre-formed DSA; graft loss inevitable
• Delayed graft function: especially DCD; requires temporary dialysis
• Surgical: bleeding, vascular thrombosis, urine leak, lymphocele

Early (1 week – 3 months):

• Acute T-cell mediated rejection: rising creatinine, tenderness over graft
• Acute antibody-mediated rejection: DSA + histological evidence
• CMV infection/reactivation: fever, leucopenia, hepatitis, colitis
• UTI: most common post-transplant infection
• Drug toxicity: CNI nephrotoxicity

Late (>3 months):

• Chronic allograft nephropathy: progressive fibrosis, declining GFR
• BK virus nephropathy: reactivation of polyomavirus; graft dysfunction
• Cardiovascular disease: accelerated atherosclerosis
• Malignancy: skin cancer (SCC >> BCC), PTLD (EBV-driven lymphoma)
• Recurrent disease: IgA nephropathy, FSGS, membranous, aHUS

Red Flags

• Rising creatinine post-transplant → biopsy to differentiate rejection vs CNI toxicity vs BK virus
• Fever + leucopenia → CMV reactivation
• New lymphadenopathy → PTLD
• New skin lesion → SCC (refer dermatology urgently)

Pre-Transplant Assessment

• Blood group and HLA typing
• Crossmatch and PRA screening
• Virology: CMV, EBV, HIV, hepatitis B/C, VZV
• Cardiac assessment: ECG, echocardiogram ± stress testing/angiography
• Cancer screening: age-appropriate (breast, cervical, prostate, bowel)
• DTPA/MAG3 renogram: native kidney function assessment
• Urodynamics: if lower urinary tract dysfunction suspected

Post-Transplant Monitoring

• Daily U&Es: early post-transplant
• Tacrolimus trough levels: target 5-8 ng/mL (centre-specific)
• CMV PCR: weekly for 3 months (if mismatch D+/R-)
• BK virus PCR: monthly for first year
• Urine PCR: proteinuria monitoring
• Transplant USS: baseline and if graft dysfunction

Transplant Biopsy

• Gold standard for graft dysfunction
• Banff classification: grades rejection severity
• Distinguishes: T-cell mediated rejection, antibody-mediated rejection, CNI toxicity, BK nephropathy, recurrent disease

Immunosuppression

Induction:

• Basiliximab (anti-IL-2R mAb): 20mg IV day 0 and day 4 (standard)
• Anti-thymocyte globulin (ATG): for high immunological risk patients

Maintenance (triple therapy):

• Tacrolimus 0.1-0.15mg/kg BD (target trough 5-8 ng/mL by 3 months)
• Mycophenolate mofetil 500mg-1g BD
• Prednisolone: 20mg tapering to 5mg by 3 months; some centres practise steroid withdrawal

Acute T-Cell Mediated Rejection:

• IV methylprednisolone 500mg daily × 3 days
• If steroid-resistant: ATG (anti-thymocyte globulin)

Acute Antibody-Mediated Rejection:

• Plasma exchange + IV immunoglobulin + rituximab
• ± Bortezomib, eculizumab in refractory cases

BK Virus Nephropathy:

• Reduce immunosuppression (lower tacrolimus, switch MMF to leflunomide)
• No proven antiviral treatment
• Monitor BK PCR; aim for viraemia clearance

Infection Prophylaxis

• CMV: valganciclovir 900mg OD for 3-6 months (D+/R- highest risk)
• PCP: co-trimoxazole 480mg OD for 6-12 months
• Candida: nystatin mouth rinse for 1 month

Long-Term Care

• Cardiovascular: statin, BP control (<130/80), diabetes management
• Cancer surveillance: annual skin checks; PTLD awareness
• Bone health: vitamin D, DEXA scan
• Vaccination: annual influenza, pneumococcal, COVID-19 (avoid live vaccines)

Referral Criteria

• All CKD G4-5 patients should be assessed for transplant suitability
• eGFR <20: formal transplant workup
• Living donor enquiries: contact local transplant centre

• Living donor graft survival: 1-year 97%, 5-year 90%, 10-year 80%
• Deceased donor graft survival: 1-year 93%, 5-year 85%, 10-year 65%
• Patient survival post-transplant: significantly better than remaining on dialysis
• Median graft survival: ~12-15 years (living), ~10-12 years (deceased)
• Leading cause of death: cardiovascular disease (~30%)
• Leading cause of graft loss: chronic allograft nephropathy and death with functioning graft
• Return to dialysis: ~5-8% per year after first decade

Immunosuppression Side Effects

Post-Transplant Malignancy Risk