Organ transplantation: principles and complications

• Transplantation replaces a failing organ with a healthy one from a living or deceased donor; the whole field exists to move carefully from donor identification to a working graft inside a living recipient.
• Donors are living (often a kidney or part of a liver) or deceased: after brain death (DBD) or after circulatory death (DCD), and the exact determination of death follows national and local protocols.
• A good match depends on blood group compatibility, HLA type and antibodies, organ size and the health of the donor organ; the closer the match, the lower the risk of rejection and of harmful immunosuppression.
• A standard regimen lowers the immune response with an induction antibody and then long-term "triple therapy" (a calcineurin inhibitor, an antimetabolite and a steroid), tapered to the least dose that keeps the graft.
• Lifelong immunosuppression buys the graft but costs infection, cancer and drug toxicity; kidney, liver, heart and lung transplants differ in urgency, tolerance and long-term surveillance.

By the end of this page you should be able to:

1. Classify donors as living, deceased after brain death (DBD) or deceased after circulatory death (DCD), and say why the distinction changes donor management.
2. Outline the steps from donor referral and allocation to implantation and early graft monitoring.
3. Explain HLA, panel-reactive antibody and crossmatch testing in plain words, and describe the main size-matching issues in heart and lung transplantation.
4. Outline kidney, liver, heart and lung transplantation: who it is for, the operation in outline, and the early priorities.
5. Name the standard induction and maintenance immunosuppressants with a typical example dose and their main toxicities.
6. Recognise the serious post-transplant infections (CMV) and malignancies (PTLD, skin cancer) with their timings and prevention.
7. Name the roles of KDIGO, the British Transplantation Society and ISHLT, and say where transplant rejection and graft-versus-host disease are covered elsewhere.

Transplantation is the treatment of choice for end-stage failure of kidney, liver, heart and lung when medical therapy cannot keep a person alive or well. It is possible only because medicine can now support a person through major surgery, prevent rejection and manage the long-term complications of suppressed immunity. Every transplant is a balance: enough suppression to keep the graft, not so much that the recipient dies of infection or cancer. That balance, not the surgery alone, is what makes the difference between a graft that works for twenty years and one that fails.

This page is a pathway topic. It follows the whole journey, from the donor to the clinic years later, and points you to the separate MedGrasp topic "Transplant medicine: rejection and graft-versus-host disease" for the immune details of rejection and GVHD, which are covered there in depth.

Transplantation happens in four places at once.

• In the donor. A living donor gives a kidney, part of a liver, or sometimes a lobe of lung, and then goes home. A deceased donor is diagnosed with death by neurological criteria (brain death) or progresses through planned withdrawal of life-sustaining treatment to circulatory death, after which organs are retrieved under national protocols.
• In the recipient before the operation. Evaluation of end-organ failure, comorbidity, infection and cancer screening, psychological readiness and fitness for surgery; listing on a waiting list with a priority determined by medical urgency and sometimes biological factors such as blood group and sensitisation.
• In the operating theatre. Retrieval, preservation (machine perfusion is increasingly used, particularly for donation after circulatory death), implantation and reperfusion, with careful attention to ischaemia time.
• In the clinic afterwards. Immunosuppression, graft monitoring, infection prevention, malignancy surveillance, and support with adherence, for the life of the graft.

A working transplant is the end product of a chain; weak links anywhere along it show up later as graft loss.

A point that is easy to overlook: ischaemia time matters. A longer cold ischaemic time is associated with primary graft dysfunction, and in heart transplantation a median ischaemic time of 3.2 hours or more has been associated with that complication in reviews.^[2] Machine perfusion and careful logistics exist to shorten that exposure, particularly for donation after circulatory death.

Living donation is the best option where it is possible, because it can be timed before the recipient becomes critically ill and usually gives the best graft function.

• Kidney: the commonest living donation. One kidney is removed from a healthy person; the donor's remaining kidney provides adequate function for life.
• Liver: usually the smaller left lateral segment or right lobe, depending on donor and recipient size.
• Lung: now uncommon; segments from two donors may be needed for one recipient.
• Evaluation includes ABO compatibility, thorough medical and psychological assessment, imaging of vessels, and informed consent. The risk to the donor is small but real (peri-operative morbidity and, rarely, mortality) and lifelong health follow-up is expected.

Deceased donation follows one of two pathways.

• Donation after brain death (DBD). Brain death is declared using national criteria (clinical examination of brainstem reflexes, sometimes with ancillary tests such as cerebral angiography, CT angiography or EEG, depending on law and practice). After declaration the donor is maintained on ventilation and circulation while organs are assessed and retrieved. DBD donors are haemodynamically supported and can donate heart, lungs, liver, kidneys, pancreas, intestine and tissues.
• Donation after circulatory death (DCD). Life-sustaining treatment is withdrawn in a planned way; after circulatory arrest and a stand-off period, death is confirmed and organs are retrieved rapidly. DCD expands the donor pool substantially, but warm ischaemia is greater and some organs tolerate it better than others: kidneys and liver tolerate it relatively well, while heart and lung DCD programmes are developing with specialised perfusion techniques. National and local protocols govern consent, family support and the exact withdrawal and stand-off procedure.
• Expanded criteria and donation after prior infection or malignancy. Older donors and donors with certain infections or small, treated tumours can donate selected organs; the specific criteria are set by national programmes and units, and the usable organ set shrinks as donor comorbidity grows.

Two sources we opened reported survey data on donor referral systems among kidney transplant professionals: deceased-donor referral systems were rated as effective by most respondents (over 70%), for both donation after brain death and donation after circulatory death, and were supported by established medical guidelines, though death-determination protocols, consent processes and donor-management details varied between centres.^[1]

Low-resource programmes rarely have access to comprehensive HLA typing, solid-phase antibody testing or sensitive flow-cytometric crossmatching; a "minimum viable immunology" package (HLA typing, antibody screening, CDC crossmatch, reliable biopsy with C4d) and staged upgrades are the realistic route.^[7]

Matching has four components, and each has an organ-specific flavour.

1. ABO blood group. Incompatibility usually prevents transplantation of an organ to a recipient with the corresponding pre-existing antibodies, although specialised desensitisation protocols exist for kidney and liver.
2. Human leukocyte antigen (HLA) type and antibodies. Donor and recipient are typed; the recipient's serum is screened for antibodies (panel-reactive antibody screen). Donor-specific antibodies (DSAs) raise the risk of antibody-mediated rejection and are the reason sensitised recipients (from prior transplant, pregnancy or transfusion) need special handling.
3. Crossmatching. The classical complement-dependent cytotoxicity crossmatch (CDC-XM) detects complement-fixing antibodies with high specificity but limited sensitivity; flow cytometric crossmatch (FC-XM) is more sensitive but can pick up non-HLA or assay-related binding; virtual crossmatch integrates donor HLA typing, recent recipient antibody testing, exposure history and clinical context. Mean fluorescence intensity on single-antigen bead assays is semi-quantitative and is influenced by several technical factors, so no single number should decide allocation or immunosuppression.^[5]
4. Size and anatomy. Particularly important for heart and lung. Predicted heart mass (from height, weight, age and sex) is used to match donor and recipient heart size; undersizing is associated with poor function. Lung size matching by predicted total lung capacity is standard.

A few organ-specific notes on matching:

• Kidney: the degree of HLA mismatch is consistently one of the strongest predictors of long-term graft survival, and sensitisation from prior transplant, pregnancy or transfusion must be detected before listing. Matching is therefore integrated with risk stratification.
• Heart: HLA is generally not a strict selection criterion for a donor heart because of time pressure, but HLA-DR mismatches are linked to cardiac allograft vasculopathy. The International Society for Heart and Lung Transplantation (ISHLT) recommends routine HLA antibody testing in waitlisted candidates and endomyocardial biopsy grading of rejection.^[2] Pre-transplant pulmonary vascular resistance is also assessed, since high values increase post-transplant right heart failure risk.
• Lung: HLA sensitisation matters and, together with donor size and ischaemia time, drives late graft problems including chronic lung allograft dysfunction.
• Liver: the liver is comparatively immunologically tolerant and short cold ischaemic times are less of a problem; ABO compatibility is the usual hard rule, with splits and reduced-size livers possible for small recipients.

Who it is for: end-stage chronic kidney disease, usually eGFR under 10-15 mL/min/1.73 m2, with the option of pre-emptive transplant before dialysis where living donation or a timely deceased donor is available. KDIGO (Kidney Disease: Improving Global Outcomes) guidance covers candidate evaluation, living donation and recipient care.^[6]

The operation: the donor kidney is placed in the iliac fossa, the renal vessels joined to the iliac vessels and the ureter joined to the bladder; a native kidney is usually left alone. Cold ischaemic time should be minimised.

Early priorities: good urine output, rising creatinine stabilising, antihypertensive and fluid management, drug levels in range, infection prophylaxis (CMV, Pneumocystis).

Who it is for: acute or chronic liver failure, hepatocellular carcinoma within accepted tumour-burden criteria (such as the Milan criteria used by many programmes), cholestatic and metabolic disease, and selected metabolic liver disorders. Severe extrahepatic disease, active untreated malignancy and ongoing substance misuse are usual contraindications.

The operation: orthotopic replacement with the donor liver placed in the normal anatomical position, with vascular and biliary reconstruction. Reduced-size and split-liver techniques allow paediatric and small adult recipients and two recipients from one donor.

Early priorities: haemodynamic and coagulation support, bile duct and vascular patency, trough levels, nutrition, and vigilance for primary non-function or arterial thrombosis (an emergency).

Who it is for: advanced heart failure (stage D, roughly New York Heart Association class IIIb-IV) despite optimal medical and device therapy, with no irreversible end-organ failure or uncontrolled malignancy. Selection uses prognostic scores and haemodynamic assessment; roughly 53% of recipients live 10 years or more after transplantation.^[2]

The operation: orthotopic replacement on cardiopulmonary bypass; management of ischaemia time and of right ventricular dysfunction in the early post-operative period.

Early priorities: haemodynamic stability, graft function, immunosuppression initiation without worsening renal function, infection prophylaxis, and (where used) induction therapy. About half of heart recipients receive a short course of induction therapy (commonly an interleukin-2 receptor antagonist such as basiliximab, or polyclonal anti-thymocyte globulin given at 1.5 mg/kg daily for 5 days, as used in some programmes).^[2]

Who it is for: end-stage parenchymal or pulmonary vascular lung disease, such as chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, pulmonary arterial hypertension and alpha-1 antitrypsin deficiency, when life expectancy on medical therapy is short.

The operation: single or bilateral lung replacement, usually through a sternotomy or thoracotomy incision, on or off cardiopulmonary bypass.

Early priorities: airway and bronchial anastomosis care, early extubation when possible, surveillance for primary graft dysfunction, tailored infection prophylaxis (especially for cystic fibrosis recipients) and early mobilisation.

Both heart and lung transplantation are regulated and studied internationally under the ISHLT, which publishes guidelines on candidate selection, immunosuppression and long-term surveillance. Equitable global access is a stated priority of the ISHLT and of its member centres.^[3]

Where regional rules differ, consult the transplant unit and the national programme. Major guideline families include KDIGO and ERBP for kidney, BTS (British Transplantation Society) living-donor kidney guidelines (4th edition, 2017, cited widely in kidney practice), ESOT, the American Society of Transplantation, KDIGO candidate and living-donor guidelines, and ISHLT for thoracic organs.^[1][4]

The single most useful fact to hold onto is that every regimen combines agents that act at different points and accepts each one's toxicity in exchange for lower overall exposure.

Induction (peri-operative, early): intense short-term suppression. Interleukin-2 receptor antagonists (basiliximab) blocks the IL-2 receptor on activated T cells; polyclonal anti-thymocyte globulin (ATG) depletes T cells. Induction reduces early rejection and can allow steroid tapering and delayed introduction of nephrotoxic drugs. Induction carries real risks (infection, cytokine release, anaphylaxis) and is often reserved for high-risk recipients.

Maintenance (lifelong "triple therapy")^[2][4]:

• Calcineurin inhibitor: tacrolimus (more potent, generally less nephrotoxic) or cyclosporine. Mechanism: inhibits calcineurin and stops T-cell activation.
• Antimetabolite: mycophenolate mofetil (or azathioprine). Mechanism: blocks purine synthesis and T- and B-cell proliferation.
• Corticosteroid: prednisone, usually tapered toward 5 mg daily by six to twelve months (heart programmes in particular describe this taper), then individualised.

Alternatives and adjuncts: mTOR inhibitors (sirolimus, everolimus) can replace or reduce calcineurin inhibitor exposure and preserve renal function; belatacept (costimulation blockade) is less nephrotoxic but is essentially restricted to EBV-positive recipients because of post-transplant lymphoproliferative disorder risk and is not approved for de novo liver transplantation. mTOR-inhibitor conversion has also been studied to reduce rejection and vascular complications.

Toxicities that limit each drug, with the mechanism behind them:

Doses are typical adult maintenance doses described in open reviews and label-level sources and are always individualised by the transplant team: start-low in renal impairment, monitor drug levels (trough levels for tacrolimus and cyclosporine), watch creatinine, blood pressure, glucose and full blood count, and reduce or switch when toxicity appears. Check your local formulary and unit protocol before applying any figure.

• ABO and HLA typing of donor and recipient (including high-resolution typing where available).
• Antibody screen (panel-reactive antibody, cPRA) and donor-specific antibody testing by Luminex single-antigen beads.
• Crossmatch (CDC, flow cytometry, or virtual).
• Drug trough levels for calcineurin inhibitors, mTOR inhibitors.
• Graft function tests: creatinine and eGFR (kidney), bilirubin and transaminases and INR (liver), echocardiography and biomarkers (heart), spirometry and arterial blood gases (lung).
• Infection surveillance: CMV and EBV PCR where indicated, BK virus urine or plasma PCR in kidney recipients.
• Biopsy (renal, hepatic, cardiac endomyocardial) is the gold standard when function falls and the cause is uncertain.

Infection is the leading cause of hospitalisation and an important cause of death after transplantation. Long-term immunosuppression reactivates and invites CMV, EBV, HBV, BK polyomavirus, HEV, Pneumocystis, fungi and tuberculosis, among others. Reduction of immunosuppression restores some immune function and is a standard part of treating significant infection.

CMV is the single most important pathogen after solid organ transplantation. Two prevention strategies are used: universal prophylaxis (antivirals for at-risk recipients, from within 7 to 10 days of transplant for 3 to 6 months) or preemptive therapy (weekly CMV DNA monitoring, treatment when DNAemia appears). For D-positive/R-negative kidney recipients, guidelines recommend 6 months (200 days) of universal prophylaxis because this reduces CMV disease compared with 100 days; 100 days is recommended for seropositive recipients. Treatment lasts at least 21 days, with ganciclovir or valganciclovir preferred; foscarnet, cidofovir and maribavir are reserved for resistant or refractory disease, and reduction of immunosuppression is an integral part of treatment.^[8]

Other viral threats (BK polyomavirus nephropathy in kidney recipients, EBV-driven disease, hepatitis B and C reactivation) are monitored by centre protocol, usually by targeted PCR screening in the first year and after changes in immunosuppression.

Skin cancer is the most common cancer in fair-skinned transplant recipients: transplant recipients have a 65- to 250-fold increased risk of squamous cell carcinoma and a 10- to 16-fold increased risk of basal cell carcinoma, with increased melanoma risk as well. Ultraviolet radiation is the dominant risk factor, alongside fair skin, male sex and older age. Prevention therefore combines sun protection, regular skin examination and early removal of suspicious lesions.^[10]

Post-transplant lymphoproliferative disorder (PTLD) is the most serious lymphoid complication, representing roughly 21% of post-transplant malignancies. Incidence is 1% to 20% depending on the organ, with per-procedure rates highest for intestinal and multiorgan transplants and the highest absolute case burden in kidney recipients. There is an early EBV-driven peak at 12 to 24 months and a late peak at 5 to 10 years with more EBV-negative cases. Management is sequential: reduction of immunosuppression first, then rituximab, then R-CHOP for refractory or high-risk disease. EBV-seronegative recipients of organs from EBV-positive donors are a key at-risk group, and mTOR-inhibitor-based maintenance may reduce risk. Checkpoint inhibitors are generally avoided because of high rejection rates.^[9]

Other increased cancers include Kaposi sarcoma and solid cancers related to oncogenic viruses; the overall risk is set by the intensity and duration of immunosuppression.

• Primary (or delayed) graft dysfunction: poor function in the first hours to days, especially after DCD and prolonged ischaemia.
• Rejection: hyperacute (minutes to hours, pre-existing antibodies), acute cellular or antibody-mediated (often in the first year), and chronic (months to years, fibrosis, vasculopathy). Rejection is covered in detail in "Transplant medicine: rejection and graft-versus-host disease".
• Graft-versus-host disease (GVHD) is the mirror image: donor immune cells attack recipient tissues. It occurs mainly after haematopoietic stem cell transplant but has been described after solid organ transplant and after blood transfusion (transfusion-associated GVHD); it is covered in "Transplant medicine: rejection and graft-versus-host disease".
• Vascular complications: arterial or venous thrombosis at anastomoses (hepatic artery thrombosis after liver transplant is an emergency), haemorrhage, pseudoaneurysm.
• Biliary complications after liver transplant, bronchial anastomotic problems after lung transplant, cardiac allograft vasculopathy after heart transplant.
• Metabolic and bone disease: diabetes after transplant is common (4-25% of kidney and 4-40% of heart transplant patients, with risk driven by steroids and agents such as tacrolimus and sirollimus), dyslipidaemia, and bone loss from steroid use and pre-existing renal bone disease. ^[2]
• Cardiovascular disease and hypertension are the leading late causes of morbidity and death, especially after kidney transplant.
• Nephrotoxicity from calcineurin inhibitors is the central toxic dilemma of kidney transplantation in particular.

• KDIGO (Kidney Disease: Improving Global Outcomes) provides widely used guidance on kidney transplant candidate evaluation, living donation and the care of recipients (immunosuppression, graft monitoring, prevention and treatment of infection, cardiovascular disease, malignancy and other complications), using GRADE methods. The 2009 recipient guideline is co-chaired by Bertram L. Kasiske and Martin G. Zeier.^[6] KDIGO and other frameworks (ERBP, BTS, ISHLT) are named in kidney transplant best-practice reviews.^[1]
• British Transplantation Society (BTS) publishes widely used living-donor kidney transplantation guidelines and others; BTS guidance is named in kidney practice reviews.^[1]
• ISHLT (International Society for Heart and Lung Transplantation) publishes guidelines for thoracic transplantation, including candidate selection, immunosuppression and rejection surveillance, and issued updated heart transplant guidelines in 2023-2024.^[2][3]
• Other families consulted by programmes: ERBP, ESOT, the American Society of Transplantation, UNOS/OPTN in the United States, and national organ-donation organisations.

• Children: rarer indications, growth considerations, and different infection and malignancy patterns (high EBV and PTLD risk).
• Pregnancy: transplant recipients who conceive need specialist multidisciplinary care; women of reproductive age should be counselled before listing.
• Older recipients and donors: benefit and risk are carefully weighed; older donor age is associated with poorer graft function in some series.
• Low-resource settings: restricted access to HLA typing, antibody assays and sensitive crossmatching is the norm. The realistic response is a minimum viable immunology package, robust biopsy and C4d capacity, strong infection prophylaxis, sun-protection education and staged, affordable upgrades rather than imported high-cost technology. Global bodies (including ISHLT) identify workforce, infrastructure and equity as priority targets.^[3][7]

• Transplantation replaces a failing kidney, liver, heart or lung with a graft from a living or deceased donor.
• Deceased donors arrive either after brain death (DBD) or after circulatory death (DCD); death determination and donor management follow national protocols.
• Matching combines ABO, HLA and donor-specific antibodies, crossmatching (CDC, flow cytometry, virtual) and organ size; HLA mismatch and sensitisation are the central immunological risks for kidney grafts.
• Kidney, liver, heart and lung transplants differ in immunological tolerance, ischaemia tolerance and long-term surveillance; the liver is relatively tolerant, while cardiac allograft vasculopathy accounts for roughly 60% of mortality after heart transplant. ^[4]
• Standard maintenance immunosuppression is triple therapy (calcineurin inhibitor, antimetabolite, steroid), often with induction early on.
• Tacrolimus is generally more potent and less nephrotoxic than cyclosporine; mycophenolate has fewer side effects than azathioprine; belatacept is nephrotoxicity-sparing but EBV-restricted.
• Prednisone and other steroids are tapered; maintenance doses are individualised by drug levels and toxicity.
• Infection (CMV above all) and malignancy (skin cancer, PTLD) are the price of lifelong immunosuppression and require proactive screening.
• CMV prevention uses universal prophylaxis (6 months for D+/R- kidney recipients, 100 days for R+) or preemptive therapy; treatment lasts at least 21 days.
• PTLD peaks at 12-24 months (EBV-driven) and 5-10 years; treatment is reduction of immunosuppression, then rituximab, then R-CHOP.
• Skin cancer risk is 65- to 250-fold (SCC) and 10- to 16-fold (BCC); sun protection and surveillance are essential.
• KDIGO, the British Transplantation Society and ISHLT are the principle guideline families named in transplant practice, alongside ERBP, ESOT and UNOS/OPTN.
• Cross-reference: immune rejection and GVHD are covered in detail in "Transplant medicine: rejection and graft-versus-host disease".

Transplantation overlaps with the MedGrasp topics on renal failure and dialysis, liver failure and hepatocellular carcinoma, advanced heart failure and cardiac surgery, respiratory disease, infections in immunocompromised hosts (CMV, EBV, BK virus), malignancy (lymphoma, skin cancer, Kaposi sarcoma), anticoagulation and supportive care, and the dedicated topic "Transplant medicine: rejection and graft-versus-host disease". In the absence of verified topic links here, navigate through the discipline hubs, or search those titles.