Medicine – Renal Transplantation

Renal transplantation, or kidney transplantation, is an established treatment for end-stage kidney disease (ESKD). A functioning donor kidney is transplanted into the recipient, restoring renal filtration and many of the endocrine and metabolic functions of the kidneys.

For suitable patients, kidney transplantation generally provides better long-term survival and quality of life than remaining on dialysis, although recipients require lifelong monitoring and usually long-term immunosuppression.

1. Indication for Renal Transplantation

The principal indication is:

End-stage kidney disease.

Patients may reach ESKD because of conditions such as:

Diabetic kidney disease.

Glomerulonephritis.

Polycystic kidney disease.

Hypertensive kidney disease.

Congenital or hereditary renal disorders.

2. Timing of Transplantation

Transplantation can occur after a patient has started:

Haemodialysis

or

Peritoneal dialysis.

However, when possible, transplantation may be performed before long-term dialysis becomes necessary.

This is called:

Pre-emptive kidney transplantation.

3. UK Transplant Numbers

The original note states:

“In the UK, 2000 patients per year.”

This is an old historical figure and should not be memorised as a current fixed number.

The number of kidney transplants performed each year changes according to:

Organ availability.

Living donation.

Deceased donation.

Waiting-list activity.

Transplantation policy.

For examinations, the principles of transplantation are usually more important than an old annual transplant number.

4. Sources of Donor Kidneys

Kidneys may come from:

Living donors

or

Deceased donors.

Both are important sources of transplantable kidneys.

5. Living Donors

Living donors may include:

Biologically related donors.

Spouses or partners.

Friends or other suitable individuals.

Living donation has become considerably more important than the historical figure of:

10–15% of transplants

suggests.

Therefore, that percentage should be regarded as outdated rather than a current universal figure.

6. Advantages of Living-Donor Transplantation

Living-donor transplantation has several potential advantages.

These include:

Planned timing of surgery.

Shorter cold-ischaemia time.

Possibility of pre-emptive transplantation.

Generally excellent graft outcomes.

The donor must undergo careful medical and psychological assessment to ensure that donation is acceptably safe.

7. Deceased Donors

Deceased-donor kidneys may be obtained after:

Donation after brain death

or

Donation after circulatory death.

Allocation depends on multiple factors, including compatibility and national allocation policies.

8. Graft Survival

The original figures state:

90% graft survival at 1 year

and

70% at 5 years.

These are historical figures and should not be treated as current universal survival rates.

Modern graft survival varies according to:

Living versus deceased donation.

Recipient characteristics.

Donor characteristics.

Immunological risk.

Definition of graft survival used.

Transplant era and centre.

In general, modern outcomes are better than many older textbook figures suggest.

9. Pre-Transplant Assessment

Before transplantation, both recipient and donor require careful assessment.

The recipient is evaluated for:

Cardiovascular disease.

Active infection.

Malignancy.

Immunological compatibility.

Ability to tolerate surgery and immunosuppression.

Other major comorbidities.

10. ABO Blood-Group Compatibility

Traditionally, the donor and recipient should be:

ABO compatible.

This reduces the risk of antibodies in the recipient attacking blood-group antigens expressed by the graft.

11. Rhesus Factor

The original note correctly states:

Rhesus matching is not important in kidney transplantation.

Unlike red-cell transfusion:

Rh compatibility is not a major requirement for renal transplantation.

Therefore:

ABO matters; Rh generally does not.

12. ABO-Incompatible Transplantation

An important modern development is that:

ABO incompatibility is no longer an absolute barrier in selected patients.

Specialist programmes may use:

Antibody removal

and

Immunosuppressive strategies

to permit selected ABO-incompatible living-donor transplants.

However, ABO-compatible transplantation remains simpler and preferable when available.

13. HLA System

Another important part of transplantation immunology is:

Human leukocyte antigen – HLA – matching.

HLA molecules are important components of the immune system and help distinguish:

Self from non-self.

Differences between donor and recipient HLA can trigger immune recognition of the transplanted kidney.

14. HLA Genes

The major HLA genes are located on:

Chromosome 6.

More specifically, they are located within the:

Major histocompatibility complex – MHC.

15. Important HLA Types

Historically, kidney transplantation focused heavily on matching:

HLA-A.

HLA-B.

HLA-DR.

HLA-C and other loci can also have immunological relevance.

16. Historical Importance of HLA Matching

Older teaching often ranked matching approximately as:

DR > B > A > C.

HLA-DR matching was considered particularly important.

However, modern transplantation uses a much more sophisticated assessment of immunological compatibility than simply counting these mismatches.

17. Modern HLA Assessment

Modern assessment may consider:

HLA mismatches.

Pre-existing anti-HLA antibodies.

Donor-specific antibodies – DSA.

Calculated sensitisation levels.

Crossmatch results.

Therefore, a simple rule such as:

“One DR or one B mismatch is acceptable”

is too rigid for modern transplantation.

18. Sensitisation

Some recipients have previously developed antibodies against HLA antigens.

This is called:

Sensitisation.

Sensitisation may occur following:

Previous transplantation.

Pregnancy.

Blood transfusion.

Highly sensitised patients may have greater difficulty finding a compatible donor.

19. Donor-Specific Antibodies

Particular attention is given to:

Donor-specific antibodies – DSA.

These are recipient antibodies directed against HLA antigens present on the proposed donor kidney.

They increase the risk of:

Antibody-mediated rejection.

20. Crossmatching

Before transplantation, a:

Crossmatch

is performed to determine whether the recipient has antibodies capable of reacting against the donor.

A strongly positive crossmatch generally indicates a high risk of:

Hyperacute or severe antibody-mediated rejection.

21. Why Matching Matters

The purpose of compatibility testing is to reduce the risk of:

Rejection.

Early graft loss.

Chronic graft injury.

However, transplantation decisions balance immunological matching against other factors such as:

Waiting time.

Donor quality.

Recipient urgency.

22. Kidney Transplant Operation

The donor kidney is usually placed:

Extraperitoneally in the iliac fossa.

The donor renal artery and vein are connected to the recipient’s:

Iliac vessels.

The donor ureter is implanted into the:

Bladder.

23. What Happens to the Patient’s Own Kidneys?

The patient’s native kidneys are usually:

Left in place.

They are removed only when there is a particular indication, such as selected cases involving:

Recurrent infection.

Malignancy.

Severe symptoms from very large polycystic kidneys.

24. Need for Immunosuppression

The transplanted kidney contains donor antigens that can be recognised as foreign by the recipient’s immune system.

Without adequate immunosuppression, this can cause:

Graft rejection.

Therefore, most recipients require long-term:

Immunosuppressive therapy.

25. Induction and Maintenance Immunosuppression

Modern immunosuppression can broadly be divided into:

Induction therapy

and

Maintenance therapy.

Induction therapy provides strong immunosuppression around the time of transplantation.

Maintenance therapy is continued long-term.

26. Maintenance Immunosuppression

The original notes describe:

Triple therapy.

This remains an important general concept.

A common maintenance regimen includes:

A calcineurin inhibitor.

An antiproliferative agent.

Corticosteroid therapy in many protocols.

Exact regimens vary according to recipient risk and transplant centre.

27. Calcineurin Inhibitors

The main calcineurin inhibitors are:

Tacrolimus

and

Ciclosporin.

In modern practice:

Tacrolimus is commonly preferred.

28. Tacrolimus

Tacrolimus suppresses:

T-cell activation

by inhibiting:

Calcineurin.

It is highly effective at reducing acute rejection.

Important adverse effects include:

Nephrotoxicity.

Hypertension.

Hyperkalaemia.

Neurotoxicity.

Diabetes mellitus.

29. Ciclosporin

Ciclosporin is another:

Calcineurin inhibitor.

Adverse effects include:

Nephrotoxicity.

Hypertension.

Hyperlipidaemia.

Gingival hyperplasia.

Hirsutism.

30. Antiproliferative Drugs

The second major maintenance component is commonly an antiproliferative agent.

Examples include:

Mycophenolate mofetil / mycophenolic acid

or

Azathioprine.

Mycophenolate is commonly used in modern transplant regimens.

31. Mycophenolate

Mycophenolate inhibits lymphocyte proliferation.

Important adverse effects include:

Diarrhoea and other gastrointestinal symptoms.

Bone-marrow suppression.

Leukopenia.

It is also:

Teratogenic.

32. Azathioprine

Azathioprine suppresses:

Purine synthesis and lymphocyte proliferation.

Important adverse effects include:

Bone-marrow suppression.

Hepatotoxicity.

Long-term immunosuppression involving azathioprine has also been associated with increased:

Skin-cancer risk.

33. Corticosteroids

Prednisolone may form the third component of maintenance therapy.

Long-term corticosteroid adverse effects include:

Diabetes.

Hypertension.

Osteoporosis.

Weight gain.

Infection.

Cushingoid features.

Some modern protocols minimise or withdraw steroids in selected recipients.

34. Induction Therapy

At transplantation, selected patients receive powerful induction immunosuppression.

Agents may include:

Basiliximab

or

T-cell-depleting therapies such as antithymocyte globulin.

The choice depends on the recipient’s immunological risk and local protocol.

35. Major Post-Transplant Complications

Important complications include:

Rejection.

Infection.

Malignancy.

Cardiovascular disease.

Hypertension.

Metabolic complications.

Drug toxicity.

Recurrence of the original kidney disease.

36. Hyperacute Rejection

Hyperacute rejection occurs within:

Minutes to hours

after transplantation.

It results from pre-existing recipient antibodies against donor antigens.

These antibodies cause:

Complement activation.

Endothelial injury.

Thrombosis.

Rapid graft failure.

37. Prevention of Hyperacute Rejection

Modern:

Crossmatching

and

Antibody screening

have made hyperacute rejection much less common.

A severely affected graft may be irreversibly damaged.

38. Acute Rejection

Acute rejection can occur from:

T-cell-mediated rejection

or

Antibody-mediated rejection.

It may occur early after transplantation but can also occur later, particularly when immunosuppression is inadequate.

39. Presentation of Acute Rejection

Possible features include:

Rising serum creatinine.

Reduced graft function.

Reduced urine output.

Sometimes:

Graft tenderness.

Fever.

However, modern rejection may be detected primarily through:

Laboratory abnormalities.

40. Diagnosis of Rejection

Evaluation may include:

Serum creatinine.

Urinalysis.

Drug levels.

Ultrasound.

Donor-specific antibody testing.

A:

Transplant kidney biopsy

is often required to determine the exact type of rejection.

41. Chronic Graft Dysfunction

Long-term graft dysfunction can result from multiple processes rather than a single entity called simply “chronic rejection.”

Causes include:

Chronic antibody-mediated rejection.

Calcineurin-inhibitor toxicity.

Recurrent disease.

Hypertension.

Infection.

Other chronic graft injuries.

42. Infection after Transplantation

Immunosuppression increases susceptibility to:

Bacterial infections.

Viral infections.

Fungal infections.

Opportunistic infections.

The type of infection depends partly on:

Time since transplantation

and

Intensity of immunosuppression.

43. Pneumocystis Pneumonia

The original term:

Pneumocystis carinii pneumonia

is outdated in humans.

The organism causing human disease is:

Pneumocystis jirovecii.

Therefore the preferred term is:

Pneumocystis jirovecii pneumonia – PJP.

The abbreviation PCP is still sometimes encountered historically.

44. Prevention of Pneumocystis Infection

Transplant recipients commonly receive prophylaxis with:

Trimethoprim-sulfamethoxazole

for a defined period after transplantation, according to local protocol.

This reduces the risk of:

PJP.

It also provides protection against certain other infections.

45. Cytomegalovirus

Cytomegalovirus – CMV is one of the most important viral infections after transplantation.

Risk depends strongly on the:

CMV status of donor and recipient.

A particularly high-risk combination is:

CMV-positive donor → CMV-negative recipient.

46. CMV Manifestations

CMV can cause:

Fever.

Bone-marrow suppression.

Gastrointestinal disease.

Pneumonitis.

Hepatitis.

Retinitis.

Other organ involvement may occur.

47. CMV Prevention and Treatment

High-risk patients may receive antiviral prophylaxis such as:

Valganciclovir

according to transplant protocol.

Established disease is treated with appropriate:

Anti-CMV antiviral therapy.

48. BK Polyomavirus

An important modern transplant infection not mentioned in the original notes is:

BK polyomavirus.

Reactivation under immunosuppression can cause:

BK virus nephropathy.

This can progressively damage the transplanted kidney.

49. BK Virus Management

Patients may undergo monitoring for:

BK viraemia.

When significant BK infection occurs, management often requires carefully:

Reducing immunosuppression

while balancing the increased risk of rejection.

50. Malignancy after Transplantation

Long-term immunosuppression increases the risk of:

Malignancy.

This occurs because immune surveillance against malignant cells is reduced and oncogenic viral infections become more important.

51. Skin Cancer

Transplant recipients have a markedly increased risk of:

Non-melanoma skin cancer.

In particular:

Cutaneous squamous cell carcinoma

is an important long-term complication.

Sun protection and dermatological surveillance are therefore important.

52. Azathioprine and Skin Cancer

The original note associates:

Azathioprine with skin cancer.

This is a useful association, although the overall cancer risk results from:

Long-term immunosuppression as a whole

rather than one drug alone.

Azathioprine can contribute particularly to:

Photosensitisation and cutaneous carcinogenesis.

53. Post-Transplant Lymphoproliferative Disorder

The original notes list:

Non-Hodgkin lymphoma.

A more specific transplant concept is:

Post-transplant lymphoproliferative disorder – PTLD.

PTLD ranges from abnormal lymphoid proliferation to aggressive lymphoma.

54. EBV and PTLD

PTLD is often associated with:

Epstein–Barr virus – EBV.

The risk is increased by the:

Overall intensity of immunosuppression.

Therefore, it is too simplistic to attribute post-transplant lymphoma specifically to:

Ciclosporin alone.

55. Cardiovascular Disease

Cardiovascular disease remains a major cause of morbidity and mortality after kidney transplantation.

Important risk factors include:

Pre-existing CKD-related cardiovascular disease.

Hypertension.

Diabetes.

Dyslipidaemia.

Smoking.

Effects of immunosuppressive medications.

56. Ischaemic Heart Disease

The original note states:

“IHD is 10–20 times more prevalent.”

This is another historical figure that should not be treated as a fixed modern estimate.

The key point is:

Kidney-transplant recipients remain at substantially increased cardiovascular risk compared with the general population.

57. Hypertension

Hypertension is common after renal transplantation.

Possible causes include:

Pre-existing hypertension.

Calcineurin inhibitors.

Corticosteroids.

Transplant renal artery stenosis.

Chronic graft dysfunction.

Native kidney disease.

58. Post-Transplant Diabetes

Another important metabolic complication is:

Post-transplant diabetes mellitus.

Risk is increased by:

Tacrolimus.

Corticosteroids.

Pre-existing metabolic risk factors.

59. Transplant Renal Artery Stenosis

Renal artery stenosis affecting the transplanted kidney can cause:

Difficult-to-control hypertension

and

Graft dysfunction.

It should therefore be considered in a recipient who develops new or resistant hypertension.

60. Recurrence of Original Renal Disease

The original notes correctly emphasise that the disease responsible for ESKD may:

Recur in the transplanted kidney.

However, recurrence risk differs greatly between diseases.

61. Recurrent Glomerular Disease

Diseases that can recur include:

FSGS.

IgA nephropathy.

Membranous nephropathy.

MPGN / C3 glomerulopathy.

Other glomerular disorders may also recur.

62. FSGS Recurrence

Primary FSGS is particularly important because it can recur:

Very rapidly after transplantation.

The patient may develop:

Heavy proteinuria

soon after transplantation.

63. IgA Nephropathy Recurrence

IgA nephropathy can recur in the transplanted kidney.

Recurrence may be:

Histological only

or may eventually cause:

Proteinuria, haematuria, and graft dysfunction.

64. Anti-GBM Disease and Transplantation

Patients with anti-GBM disease can undergo transplantation once the disease is appropriately controlled.

Transplantation is generally delayed until:

Anti-GBM antibodies have remained undetectable for an appropriate period.

This reduces the risk of recurrence.

65. Surgical and Urological Complications

Renal transplantation can also cause surgical complications such as:

Bleeding.

Renal artery or vein thrombosis.

Urinary leakage.

Ureteric obstruction or stenosis.

Lymphocele formation.

66. Delayed Graft Function

Some transplanted kidneys do not function immediately.

This is called:

Delayed graft function.

It commonly reflects:

Acute tubular injury associated with ischaemia-reperfusion.

Temporary dialysis may be required while the graft recovers.

67. Monitoring after Transplantation

Long-term follow-up includes monitoring of:

Serum creatinine and eGFR.

Proteinuria.

Blood pressure.

Electrolytes.

Immunosuppressant drug levels.

Blood glucose and lipids.

Infection.

Malignancy.

Cardiovascular risk.

68. Renal Transplantation – Matching Note Form

ABO:

Usually compatible.

Selected ABO-incompatible transplantation is possible with specialist protocols.

Rhesus:

Not clinically important for kidney matching.

HLA:

Genes located on chromosome 6.

HLA-A, HLA-B and HLA-DR have historically been major matching loci.

Modern matching also considers broader HLA characteristics.

Donor-specific antibodies:

Increase risk of antibody-mediated rejection.

Crossmatch:

Determines whether recipient antibodies react against the donor.

A significant positive crossmatch indicates high immunological risk.

69. Renal Transplantation – Immunosuppression Note Form

Calcineurin inhibitor:

Tacrolimus commonly used.

Ciclosporin alternative.

Antiproliferative drug:

Mycophenolate commonly used.

Azathioprine alternative.

Corticosteroid:

Prednisolone used in many regimens.

Some protocols minimise steroids.

Typical concept:

Calcineurin inhibitor + antiproliferative agent ± corticosteroid.

70. Renal Transplantation – Rejection Note Form

Hyperacute rejection:

Minutes to hours.

Pre-existing antibodies.

Thrombosis and rapid graft failure.

Acute rejection:

T-cell-mediated or antibody-mediated.

Often presents with rising creatinine.

Biopsy commonly required.

Chronic graft dysfunction:

Multifactorial.

May involve chronic antibody-mediated injury, drug toxicity, recurrent disease and other causes.

71. Renal Transplantation – Infection Note Form

Pneumocystis jirovecii:

Opportunistic pneumonia.

Prophylaxis commonly used.

CMV:

Important opportunistic viral infection.

May cause systemic and organ-specific disease.

BK polyomavirus:

Can cause transplant nephropathy and graft dysfunction.

Other infections:

Bacterial, fungal and viral infections occur because of immunosuppression.

72. Renal Transplantation – Malignancy Note Form

Skin cancer:

Particularly cutaneous squamous cell carcinoma.

Strongly increased by chronic immunosuppression.

PTLD:

Post-transplant lymphoproliferative disorder.

Often associated with EBV.

Can include non-Hodgkin-type lymphomas.

73. Important Corrections to the Original Notes

The UK figure:

“2000 renal transplants per year”

is historical and should not be memorised as a current number.

The graft-survival figures:

“90% at 1 year and 70% at 5 years”

are also historical.

Modern outcomes vary by donor and recipient factors and are generally better than many older textbook figures.

The statement:

“Live donors = 10–15%”

is outdated as a universal figure.

Living donation now contributes substantially to transplantation programmes.

The old HLA rules:

“DR > B > A > C”

and

“one DR or B mismatch acceptable”

are useful historical simplifications but do not represent the full modern approach.

Modern assessment includes:

HLA compatibility + donor-specific antibodies + sensitisation + crossmatching.

The term:

Pneumocystis carinii pneumonia

should be replaced with:

Pneumocystis jirovecii pneumonia – PJP.

The association:

“Non-Hodgkin lymphoma especially with ciclosporin”

is better understood as:

PTLD, often EBV-related, associated with the overall intensity of immunosuppression.

The statement:

“All glomerulonephritides can recur”

is too broad.

Many primary renal diseases can recur after transplantation, but:

The probability, timing and clinical significance of recurrence differ substantially between diseases.

Key Clinical Pattern

For matching, remember:

ABO COMPATIBILITY + HLA ASSESSMENT + DONOR-SPECIFIC ANTIBODIES + CROSSMATCH.

For maintenance immunosuppression, think:

TACROLIMUS + MYCOPHENOLATE ± PREDNISOLONE.

For major complications, remember:

REJECTION + INFECTION + MALIGNANCY + CARDIOVASCULAR DISEASE + DRUG TOXICITY + RECURRENT RENAL DISEASE.

High-yield transplant associations:

TACROLIMUS → NEPHROTOXICITY + DIABETES.

CICLOSPORIN → NEPHROTOXICITY + HYPERTENSION + GINGIVAL HYPERPLASIA + HIRSUTISM.

AZATHIOPRINE → BONE-MARROW SUPPRESSION + SKIN-CANCER RISK.

PJP → OPPORTUNISTIC PNEUMONIA.

CMV → IMPORTANT POST-TRANSPLANT VIRAL INFECTION.

BK VIRUS → TRANSPLANT NEPHROPATHY.

EBV → PTLD.

And the central principle is:

A SUCCESSFUL KIDNEY TRANSPLANT REQUIRES A BALANCE BETWEEN ENOUGH IMMUNOSUPPRESSION TO PREVENT REJECTION AND NOT SO MUCH THAT INFECTION, MALIGNANCY AND DRUG TOXICITY BECOME EXCESSIVE.