NephrologyTier 2Topic

Renal transplantation issues - principles of assessment of potential donor transplant candidates and their understanding of the risks of transplantation

Why transplant and what assessment answers

Transplantation gives better survival and quality of life than dialysis in almost every eligible patient - so the default question is why not?, not why?
Pre-emptive transplantation (before dialysis) gives the best outcome - refer at eGFR 15-20
Assessment answers three questions:
- 1. Will the patient survive the operation and the immunosuppression?
- 2. Will the graft outlive the patient's other risks?
- 3. Can the patient adhere to lifelong therapy?

~1400 kidney transplants per year in Australia; ~1/3 living donor
Median deceased-donor waiting time in Australia ~2.5-3 years (highly sensitisation-dependent)
Living donor outcomes are better: graft half-life ~15-20 yrs vs ~12 for deceased donor
Aboriginal and Torres Strait Islander patients are transplanted at markedly lower rates than non-Indigenous patients with the same ESKD burden - a recognised equity failure

ABO blood group compatibility (ABO-incompatible transplantation is possible with desensitisation)
HLA matching - A, B, DR (and DQ); HLA-DR mismatch matters most
Calculated PRA (cPRA) / panel-reactive antibody - the proportion of donors against which the recipient has antibodies
- Sensitised by pregnancy, transfusion and previous transplantation
- A highly sensitised patient may wait years - hence avoiding transfusion in CKD
Crossmatch
- Complement-dependent cytotoxicity (CDC) crossmatch positive = absolute contraindication (hyperacute rejection)
- Flow cytometry and virtual crossmatch using single-antigen bead-defined DSA
Paired kidney exchange programmes allow incompatible pairs to be matched

Cardiac - the dominant risk. ECG, echocardiogram, functional testing or angiography in diabetes, long dialysis vintage, or symptoms
Vascular - iliac vessel imaging (CT or duplex), particularly in diabetes and prolonged dialysis (calcified vessels may make implantation impossible)
Infection screen - CMV and EBV serostatus (drives prophylaxis and PTLD risk), hepatitis B/C, HIV, syphilis, TB (IGRA + CXR), strongyloides if endemic exposure, dental review
Malignancy screen - age-appropriate (cervical, breast, bowel), skin examination (essential in Australia), urological assessment if acquired cystic disease
Urological - bladder function, reflux, prior surgery; consider native nephrectomy in ADPKD if no room
Immunological - blood group, HLA typing, cPRA and DSA
Recurrence risk of the primary disease - FSGS, MPGN/C3G, IgAN, membranous, oxalosis, aHUS
Psychosocial - adherence history, substance use, support, housing, ability to attend follow-up

Active malignancy (with defined disease-free intervals before listing)
Uncontrolled or untreated infection - including chronic suppurative lung disease such as bronchiectasis, active TB, untreated HIV with poor control
Unacceptable anaesthetic or cardiac risk / life expectancy shorter than the expected benefit
Positive CDC crossmatch against the donor
Significant unaddressed smoking, alcohol or other substance use, or psychological factors preventing adherence

Severe skin damage and high skin cancer burden - immunosuppression multiplies SCC risk 20-65x; a major issue in Australia
Severe peripheral vascular disease, particularly with diabetes - complicates graft placement and threatens limb perfusion
Documented non-adherence
Morbid obesity (higher wound complications and delayed graft function; increasingly not an absolute barrier)
Frailty, advanced age with multimorbidity, active substance use, recurrent disease with a high recurrence risk

The graft is not permanent: median half-life ~12-15 years, and most patients will need a plan for what follows
Lifelong immunosuppression, with lifelong risk of infection, malignancy and drug toxicity
Perioperative mortality ~1%; surgical complications
Skin cancer risk and the need for sun protection and annual dermatology review
Post-transplant diabetes ~15-30%
Rejection is common and usually treatable; non-adherence is a leading cause of graft loss
Fertility returns quickly after transplantation - contraception counselling; wait >=1 year before pregnancy; stop mycophenolate 6 weeks before conception
Alternatives: remaining on dialysis, or conservative kidney management

Donor safety is the priority - a healthy donor accepts risk for no personal benefit
Assess: GFR (measured, not estimated), albuminuria, blood pressure, glucose tolerance, imaging (anatomy and stones), genetic testing where the recipient's disease is heritable (ADPKD, Alport, FSGS), psychosocial evaluation with an independent donor advocate
Exclude if: reduced GFR for age, diabetes, uncontrolled hypertension, significant proteinuria, obesity with metabolic risk, or a high projected lifetime ESKD risk
Donor lifetime ESKD risk rises slightly but measurably - counsel explicitly, especially in young donors and those of African ancestry (APOL1)

Avoid transfusion where possible (allosensitisation) - use iron and ESAs instead
Vaccinate before transplantation - live vaccines (MMR, varicella, zoster) can only be given pre-transplant
Smoking cessation, weight management, dental clearance, adherence support
Re-evaluate annually while waitlisted - cardiac status and malignancy screening go stale

Cardiovascular disease - the main determinant of both candidacy and long-term outcome
Diabetes - vascular access, vascular calcification, PTDM; consider simultaneous pancreas-kidney in type 1 with ESKD
Obesity, frailty, dementia
Skin cancer - a distinctly Australian limitation
Sensitisation from pregnancy, transfusion, prior grafts
Recurrent primary disease - FSGS (highest), C3G/MPGN, IgAN, membranous, oxalosis, aHUS (eculizumab prophylaxis)
ADPKD - may need native nephrectomy for space
Social determinants - remoteness, housing, transport, carer availability; a dominant barrier for Aboriginal and Torres Strait Islander patients

1-yr graft survival >95%; median half-life ~12-15 years (deceased donor), longer with a living donor
Transplantation approximately doubles life expectancy compared with remaining on dialysis, for eligible patients
Pre-emptive transplantation gives the best graft and patient survival - every year on dialysis before transplantation worsens the outcome
Death with a functioning graft (cardiovascular, infection, malignancy) is a leading cause of graft loss
Re-transplantation is possible but sensitisation makes it harder - which is another reason to protect adherence
Patients who are declined should be re-assessed if the barrier is modifiable (weight, smoking, treated malignancy, improved cardiac status)

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