Renal Transplantation

Kidney transplantation is the preferred treatment for end-stage kidney disease. Compared with long-term dialysis, it improves survival, quality of life and cost effectiveness. Living donor transplantation gives the best outcomes, and pre-emptive transplantation before dialysis is associated with particularly favourable results.

Donor sources

• Living related or unrelated donors, including paired exchange.
• Deceased donors after brain death or circulatory death.
• Extended criteria donor organs may be used according to allocation systems and recipient risk.

Candidate selection

• Patients with advanced chronic kidney disease may be listed when eGFR falls to about 20 mL/min/1.73 m² or less.
• Contraindications include active malignancy or infection, severe irreversible cardiopulmonary or hepatic disease unsuitable for surgery, active substance misuse, major non-adherence and very limited life expectancy.
• Special issues include advanced age, obesity, HIV, hepatitis C, prior malignancy and recurrence risk of the original renal disease.

Immunology

• ABO compatibility, HLA typing and crossmatching are central to donor selection.
• Panel reactive antibodies and donor-specific antibodies assess sensitisation.
• A positive complement-dependent cytotoxicity crossmatch predicts hyperacute rejection.
• Desensitisation can allow selected ABO-incompatible or HLA-incompatible transplantation.

The graft is placed extraperitoneally in the iliac fossa, with vascular anastomoses to the iliac vessels and ureteric implantation into the bladder. Modern one-year graft survival exceeds 90% in most programmes.

Pre-transplant assessment

• Cardiovascular assessment, including ECG, echocardiography and further ischaemia testing when indicated.
• Assessment of peripheral vascular disease and iliac anatomy.
• Screening for HIV, hepatitis B and C, CMV, EBV, VZV, syphilis, tuberculosis and strongyloides where relevant.
• Age-appropriate cancer screening, urological assessment, dental review, psychosocial evaluation and vaccination.

Early complications

• Delayed graft function, especially after deceased donor transplantation.
• Bleeding, renal artery or vein thrombosis, renal artery stenosis, ureteric leak or necrosis, ureteric obstruction, lymphocele and wound infection.
• Hyperacute rejection is rare but occurs within minutes to hours.

Rejection

• Acute T-cell mediated rejection usually occurs in the first months and may present with rising creatinine, graft tenderness, fever or reduced urine output, though it can be asymptomatic.
• Antibody-mediated rejection is associated with donor-specific antibodies, microvascular inflammation and C4d staining.
• Chronic allograft dysfunction presents with progressive creatinine rise, proteinuria and hypertension.

Infection pattern

• First month: surgical site, urinary and line infections and donor-derived infection.
• One to six months: opportunistic infections including CMV, Pneumocystis, BK virus, fungi, tuberculosis and hepatitis reactivation.
• Beyond six months: community infections, urinary tract infection, herpes zoster and late CMV.

Long-term complications

• Cardiovascular disease, hypertension, post-transplant diabetes, dyslipidaemia and obesity.
• Skin cancers, post-transplant lymphoproliferative disorder, Kaposi sarcoma and anogenital malignancy.
• Bone disease, anaemia, electrolyte abnormalities, gout and tertiary hyperparathyroidism.
• Drug toxicity from calcineurin inhibitors, mycophenolate, mTOR inhibitors and corticosteroids.

Red flags include fever with graft tenderness, falling urine output, creatinine rise of about 25% or more from baseline, new proteinuria and increasing BK viral load.

Routine surveillance

• Creatinine, eGFR, electrolytes, tacrolimus trough levels, CBC, glucose, liver tests and urinalysis frequently early after transplant and at progressively wider intervals later.
• Urine protein/creatinine ratio, lipids and HbA1c.
• Donor-specific antibody surveillance in selected patients.
• BK virus PCR regularly in the first two years, and CMV PCR according to prophylaxis strategy and donor-recipient risk.

Graft dysfunction

• Exclude hypovolaemia, drug effects and obstruction.
• Graft Doppler ultrasound assesses perfusion, hydronephrosis, collections, arterial stenosis and venous thrombosis.
• CT, renography, MR angiography or catheter angiography are used according to the suspected complication.
• Ultrasound-guided graft biopsy is interpreted using Banff criteria and distinguishes T-cell rejection, antibody-mediated rejection, BK nephropathy, calcineurin inhibitor toxicity and recurrent glomerular disease.
• Urine and blood cultures, CMV and BK PCR and chest imaging are obtained when infection is suspected.

Induction immunosuppression

• Basiliximab 20 mg IV on day 0 and day 4 for low to moderate immunological risk.
• Rabbit anti-thymocyte globulin about 1.5 mg/kg daily for 3 to 5 days for high-risk recipients.
• Methylprednisolone 500 mg IV intra-operatively.

Maintenance immunosuppression

• Tacrolimus about 0.1 to 0.2 mg/kg/day in divided doses, titrated to trough level according to time from transplant and immunological risk.
• Mycophenolate mofetil 1 g twice daily, or equivalent mycophenolate sodium.
• Prednisolone tapered to low-dose maintenance in many regimens.
• Alternatives include ciclosporin, belatacept, everolimus and sirolimus in selected patients.

Prophylaxis

• Co-trimoxazole for Pneumocystis prophylaxis for 6 to 12 months.
• Valganciclovir prophylaxis according to CMV donor and recipient status, usually 3 to 6 months and longer in high-risk patients.
• Oral antifungal prophylaxis in the early post-transplant period in many programmes.
• Tuberculosis treatment or prophylaxis when latent infection is confirmed.
• Non-live vaccination; avoid live vaccines after transplantation.

Treatment of rejection

• Mild T-cell mediated rejection: methylprednisolone 250 to 500 mg IV daily for 3 days with optimisation of baseline immunosuppression.
• Steroid-resistant or vascular rejection: rabbit anti-thymocyte globulin about 1.5 mg/kg daily for several days.
• Antibody-mediated rejection: plasma exchange, IVIG, corticosteroid pulse and selected use of rituximab or other agents.

Other complications

• Delayed graft function: optimise volume, avoid nephrotoxins, dialyse when indicated and biopsy if recovery is delayed.
• Vascular thrombosis: urgent surgical exploration.
• Ureteric leak or obstruction: nephrostomy and stenting with surgical repair when required.
• Lymphocele: drainage, sclerotherapy or laparoscopic marsupialisation.
• Renal artery stenosis: angioplasty with or without stenting.
• BK nephropathy: reduce immunosuppression and monitor viral load.
• CMV disease: valganciclovir 900 mg twice daily, adjusted for renal function, or IV ganciclovir for severe disease.
• Post-transplant lymphoproliferative disorder: reduce immunosuppression and use rituximab-based therapy when indicated.

Long-term care

• Blood pressure target below 130/80 mmHg, statin therapy, glycaemic control, weight management, bone protection and cancer surveillance.
• Mycophenolate and mTOR inhibitors must be changed before planned pregnancy.
• Adherence support and lifelong transplant follow-up are essential.