11/14/24, 10\:46 AM Renal Transplantation

Renal Transplantation

Table of contents
Article 🔍
A comprehensive topic overview

Introduction

In 1954, the
1
Almost 70 years later, the kidney is the most transplanted organ across the world with 92,532 transplants taking place in
2021.
2
It is the only de
eliminating the need for dialysis, freeing the recipient from
Remarkably, the most common outcome after a kidney transplant is death with a functioning graft. 3
kidney usually outlives the patient.
In other words, the
Glossary of terms
There are some key terms to understand when discussing transplantation\:
1
Allograft\: organ or tissue transplanted from a genetically non-identical member of the same species; most kidney
transplants are allografts
Isograft\: organ or tissue transplanted from a genetically identical member of the same species (identical twin)
Xenograft\: organ or tissue transplantation from a di
played an important part in the development of transplant surgery, and many believe it will play a key role in the
future
Rejection\: response of the immune system against the transplanted organ
Graft\: the transplanted organ or tissue
Warm ischaemia time\: the period the donated organ is not perfused but remains at body temperature
Cold ischaemia time\: the period that the donated organ is not perfused and kept cold
Antibody\: protein produced by the immune system to attack speci
Antigen\: protein which stimulates the immune system to produce antibodies (antibody generating)
MHC (major histocompatibility complex)\: a group of genes that code for proteins found on all cells that help the
immune system distinguish between self and non-self
HLA (human leukocyte antigen)\: the name for the proteins coded for by the MHC in humans

Indications

As renal transplant odialysis, all patients with end stage renal failure
should be considered for transplantation unless there are absolute contraindications.
4
Ideally, the assessment for transplantation should occur pre-emptively before the patient requires renal replacement
therapy.
Therefore, all patients with chronic kidney disease stage 4 or 5 that is progressing to the point where they are likely to need
renal replacement therapy within six months, should be assessed for transplantation.
5
https\://app.geekymedics.com/notebook/2863/ 1/811/14/24, 10\:46 AM Renal Transplantation

Contraindications

Absolute contraindications

The poorer outcomes of long-term dialysis mean there are few absolute contraindications to renal transplant.
Absolute contraindications include\:
6
Untreated malignancy
Active infection
Untreated HIV/AIDS
Life expectancy \<2 years

Relative contraindications

Relative contraindications are generally related to whether the patient can tolerate surgery.
Relative contraindications include\:
6
Age (>65)
Untreated coronary artery disease
Signiobesity
It is also recommended that there be at least two years between remission and transplantation for those with a previous
diagnosis of malignancy.
6
Finally, patients who have su
medication need a thorough psychological evaluation before re-listing for transplantation.

Principles of transplantation

The biggest barrier to successful organ transplantation is the recipient’s immune system identifying a transplanted organ
as ‘foreign’ and initiating an immune response, a process known as rejection.
The main proteins the immune system uses to determine whether a response is needed are Human Leukocyte Antigens
(HLAs).
Two main methods are used to reduce the risk of rejection in renal transplant\:
Reducing the immunogenicity of the graft by assessing and matching donor and recipient HLA types b e f o r e the
operation.
Lifelong immunosuppressive medications a f t e r the operation to prevent an immune response.

Types of donors

As it is perfectly possible to live a healthy life with one functioning kidney, renal transplantation allows for living donors.
They account for 30% of all kidney transplants in the UK, and the graft is retrieved on the same day as the transplant
operation via a laparoscopic donor nephrectomy.
4
The remaining 70% of grafts are provided by deceased donors and are removed by specialist surgeons as part of the
organ retrieval team.
4

Living donors

Living donors are the gold standard for kidney transplants. They o
both graft and patient survival.
Living donation also reduces the waiting time for the recipient and allows the operation to be planned.
4

Deceased donors

Donation after brainstem death (DBD)
https\://app.geekymedics.com/notebook/2863/ 2/811/14/24, 10\:46 AM Renal Transplantation
Brainstem death occurs when brain injury has led to an irreversible loss of the capacity for consciousness and respiration,
but the use of mechanical ventilation has prevented hypoxic cardiac arrest.
7
DBD allows retrieval to occur in a controlled manner, with the organs exposed and dissected whilst the heart is still
beating, which limits the warm ischaemic time.
Donation after circulatory death (DCD)
In the UK, donation after circulatory death involves the withdrawal of life-sustaining treatment from a critically ill patient
where that treatment is deemed to be of no overall bene
8
Specialist surgeons then wait for asystole to occur (and for a further
beginning the process of organ retrieval. This leads to an increased warm ischaemic time compared to DBD retrieval,
re
grafts.
8
Expanded criteria donation (ECD)
Expanded criteria donors include those over 60 or those over 55 with comorbidities. ECD donation aims to increase the
donor pool, particularly for elderly recipients.
3
In the UK today, most deceased donor kidneys are from ECD or DCD donors in an attempt to keep up with demand.

Assessment of the kidney transplant recipient

Kidney transplant recipients need a thorough work-up to ensure they are healthy enough to undergo the operation and
receive a well-matched kidney.
ABO blood group\: as with a blood transfusion, the kidney needs to come from a donor with a compatible blood group.
HLA typing\: the most important HLAs for renal transplant are DR, A and B. HLA typing (also known as tissue typing) is
reported as the number of mismatches between these antigens, with higher mismatches associated with poorer graft
outcomes.
9
Donor-speci
to exposure to ‘foreign’ tissue via previous organ transplantation, blood transfusion or pregnancy. This is known as
sensitisation, and it can be much harder for highly sensitised individuals to
antibodies is one reason it is essential to try to match HLA types between donors and recipients, particularly for younger
patients who are likely to need a second transplant in the future.
9
Infection screen\: due to the need for ongoing immunosuppression after transplant, patients are screened for infections
including HIV, hepatitis B & C, CMV, EBV and VZV.
General health\: as with any major operation, heart and lung function is assessed to ensure the patient can cope with the
surgery.
Psychological evaluation\: transplantation and subsequent management can be psychologically demanding, making
evaluation important. There also needs to be con
regime and medication.

Organ allocation

In an ideal world, each patient requiring a kidney transplant could provide a well-matched living donor. If this is not
possible, kidneys are allocated in two main ways.

This system matches incompatible donor/recipient pairs with another pair to overcome the mismatch, a process known as
paired donation when two pairs are involved, and pooled donation if the chain is longer.
Living donor kidney matching runs are performed four times per year, allowing more transplants to be performed with
grafts from living donors and their associated favourable outcomes.
9
Chains can also be started by altruistic donors who o

National transplant list

Demand for deceased donor kidneys outstrips supply, with over 5,000 people waiting for a graft in the UK.
4
https\://app.geekymedics.com/notebook/2863/ 3/811/14/24, 10\:46 AM Renal Transplantation
Therefore, a fair and transparent system is required to allocate these organs where they bene
All candidates who cannot
algorithm to match them with deceased donor kidneys as they become available.
The algorithm considers how well-matched the donor and recipient are in terms of ABO/HLA types and age, as well as
incorporating the time the patient has spent on the transplant list/dialysis, the location of the hospital and how di
would be for this patient to get another kidney (for example, if they have a rare blood type or are sensitised to many
potential donors).
4
The average waiting time for a deceased donor kidney on the national transplant list is two and a half years.
10

Operation

Kidney transplant surgery usually takes between two and four hours. A Rutherford-Morrison incision is made in the
recipient’s iliac fossa, usually on the right, and the surgeon dissects down to expose the external iliac vessels.
Meanwhile, the donor kidney is prepared on the backbench. Leaks are checked for, and accessory vessels are tied o
ensure graft implantation is as straightforward as possible.
The kidney is placed in the iliac fossa, and three important anastomoses are made; between the renal vessels and their
external iliac counterparts and the donor ureter and recipient bladder. A stent is usually placed in this
removed two to six weeks later via cystoscopy.
10
The donor kidney is positioned in the extraperitoneal space, and the native kidneys are usually left in place.
11
Figure 1. Kidney transplant operation diagram
https\://app.geekymedics.com/notebook/2863/ 4/811/14/24, 10\:46 AM Renal Transplantation
Figure 2. A kidney for transplant from live donor

Post-operative care

After the operation, the patient will have regular serum creatinine measurements to assess renal function and appropriate
pain relief.
Polyuria is also common after renal transplant; appropriate IV
graft.
12
Most patients can leave the hospital after a week, but twice-weekly follow-up appointments are needed in the

Immunosuppression

All kidney transplant patients (apart from those receiving isograft transplants from an identical twin) will require life-long
immunosuppression.
3
A combination of medications is given to achieve the required suppression levels with an acceptable side e
A common combination is triple therapy with a steroid (e.g. prednisolone), a calcineurin inhibitor (e.g. tacrolimus) and an
anti-metabolite (e.g. mycophenolate mofetil).
However, the exact combination is tailored to the immune system of the patient, the immunogenicity of the graft and the
preferred regime of the individual transplant centre.
After three to six months, the risk of rejection goes down, and doses can usually be reduced. 3
The main risks of long-term
immunosuppression are malignancy and infection, with additional side e
Table 1. Common immunosuppressants used in renal transplantation.
Class Example Mechanism Side e
Corticosteroid Prednisolone
Calcineurin
inhibitor*
Ciclosporin
Tacrolimus
Reduces transcription of
in
Inhibits T-cell activation and
proliferation
Osteoporosis
, weight gain,
hypertension
, diabetes.
Nephrotoxicity, hypertension and
hyperlipidaemia.
https\://app.geekymedics.com/notebook/2863/ 5/811/14/24, 10\:46 AM Renal Transplantation
Anti-metabolite
Mycophenolate mofetil
(MMF)
Azathioprine
Inhibits DNA replication,
particularly in lymphocytes
Anaemia, leukopenia,
gastrointestinal toxicity.
*Calcineurin inhibitors have a narrow therapeutic index and are metabolised by the CYP450 system. It is important to avoid
concurrent prescription drugs which inhibit CYP450 enzymes, such as macrolide antibiotics (e.g. erythromycin). 13
Regular
tacrolimus ‘trough’ levels are done to ensure correct dosing is achieved and maintained.

Complications

Early complications

Early complications of renal transplantation include\:
3,4
Thrombosis\: arterial or venous thrombosis can cause rapid graft failure and is identi
may need treatment from interventional radiology or further surgery.
Delayed graft function (DGF)\: 20-60% of grafts from deceased donors will not function immediately, primarily due to
acute tubular necrosis. The risk of DGF is increased by prolonged warm and cold ischaemia times. Fortunately, most
grafts will recover and ‘wake up’ within a week, but the patient may need to be placed on haemodialysis.
Infection\: 10-20% of patients may need extra antibiotics in the
chest infections
Bleeding\: like any operation, there is a risk of bleeding, and 10% of kidney transplant patients need a blood transfusion in
the
Urine leakage\: in 2-3% of patients, there may be urine leakage from the anastomosis between the donor ureter and the
recipient bladder. This can be repaired surgically.
Stenosis\: this can occur in any arterial, venous or ureteric anastomoses and may need to be treated with balloon
dilatation +/- stent insertion.

Late complications

Late complications of renal transplantation include\:
3,4,14
Cancer\: particularly cancer associated with viruses due to long-term immunosuppression. For example, transplant
patients have a higher risk of skin cancer (HPV), lymphoma (EBV) and Karposi Sarcoma (HHV8). There is also a slight
increase in other cancers due to the immune system's role in cancer surveillance. Patients should be encouraged to
attend national screening programmes and avoid sun exposure.
Infection\: increased risk of opportunistic infection due to immunosuppression, particularly CMV (cytomegalovirus) and
pneumocystis pneumonia, for which prophylactic medication may be given
Recurrence of renal disease\: the likelihood of disease recurrence depends upon the cause. Primary focal segmental
glomerulosclerosis, membranoproliferative glomerulonephritis and diabetic nephropathy have a higher risk of
recurrence.
Cardiovascular disease\: this is the most common cause of mortality after a renal transplant, accounting for 50% of
transplant patient deaths

Rejection

Rejection is a key complication of kidney transplant surgery. Depending upon the mechanism, it can occur at di
times during the post-operative period, with the risk of rejection highest in the
A percutaneous kidney biopsy is required to con
4
Hyperacute rejection
Occurs minutes to hours after the operation and leads to rapid and irreversible graft failure.
Hyperacute rejection is mediated by pre-existing antibodies against donor HLA antigens or an incompatible donor ABO
blood type. It is rarely seen in practice due to screening for sensitisation and a crossmatch test directly before the
transplant (mixing donor lymphocytes with recipient serum; a positive crossmatch is a contraindication to transplantation).
9
Acute rejection
This is the most common form of graft rejection, usually occurring in the
https\://app.geekymedics.com/notebook/2863/ 6/811/14/24, 10\:46 AM Renal Transplantation
It often results in an asymptomatic decline in graft function, so patients are screened regularly, particularly in the
weeks after the operation. Acute rejection is most commonly T-cell mediated and is usually amenable to increased
immunosuppression.
14
Chronic rejection
Rejection after at least six months with smooth muscle proliferation, interstitial
understood and is likely due to a combination of immunological damage, hypertension and chronic drug toxicity.
Unfortunately, there are limited treatment options available.
14
Prognosis following kidney transplantation
Currently, 99% of recipients who receive grafts from living donors are alive at one year and 86% at ten years,
compared to 97% and 76% for deceased donors.
4
Kidneys from living donors also tend to function longer, an average of 20-25 years, compared with 15-20 years for
kidneys from deceased donors.
4
However, improved surgical techniques and immunosuppression, along with greater compatibility between donor
and recipient as a result of more appropriate patient selection and assessment, mean that outcomes for renal
transplant from both living and deceased donors continue to improve.
3

Key points

Renal transplant is the only de
All patients progressing to a point where they are likely to need renal replacement therapy within six months should be
assessed for transplantation
There are few absolute contraindications to renal transplantation
Kidney donors can be living or deceased, with the best outcomes associated with living donors
Rejection is a key complication of renal transplant and can be hyperacute, acute or chronic, depending on the
mechanism
The risk of rejection can be reduced by ensuring the graft is well-matched to the recipient alongside lifelong
immunosuppression
The key risks of long-term immunosuppression are malignancy and infection
The most common cause of death in patients with renal transplants is cardiovascular disease
The most common outcome after a renal transplant is death with a functioning graft

References

Mezrich J. How Death Becomes Life\: Notes from a Transplant Surgeon. London\: Atlantic Books; 2019. 384 p.
Global Observatory on Donation and Transplantation. Kidney Transplants. Published in 2021. Available from\: [LINK]
Yaqoob M. Magdi & Ashmen N. Kidney and Urinary Tract Disease. In\: Feather A, Randall D, Waterhouse M, editors. Kumar
and Clark’s Clinical Medicine. 10 th
London\: Elsevier; 2021. p.1339-1408.
NHS Blood and Transplant. Kidney Transplant. Available from\: [LINK]
Thiruchelvam PTR, Willicombe M, Hakim N, Taube D, Papalois V. Renal Transplantation. BMJ. 2011 Nov 19. 343\:1055-1059.
NHS Blood and Transplant. Patient Selection for Deceased Donor Kidney Only Transplantation. Available from\: [LINK]
NHS Blood and Transplant. Donation after Brainstem Death. Published in 2023. Available from\: [LINK]
NHS Blood and Transplant. Donation after Circulatory Death. Published in 2023. Available from\: [LINK]
Kidney Care UK. Kidney Transplants\: What you need to know about blood groups, antibodies and sensitization. Published in
2023. Available from\: [LINK]
NHS.uk. Kidney Transplant. Published in 2022. Available from\: [LINK]
https\://app.geekymedics.com/notebook/2863/ 7/811/14/24, 10\:46 AM Renal Transplantation
Conway B, Phelan PJ & Stewart GD. Nephrology and Urology. In\: Penman ID, Ralston SH, Strachan MWJ, Hobson RP, editors.
Davidson’s Principles and Practice of Medicine. 24 th
London\: Elsevier; 2023. p. 557-611.
Agarwal A, Jeyarajah S, Harries R, Weerakkody R, McLatchie G & Borley N. Oxford Handbook of Clinical Surgery. 5 th
Oxford\:
OUP; 2022. 1056 p.
Wilkinson IB, Raine T, Wiles K, Goodhart A, Hall C & O’Neill H. Oxford Handbook of Clinical Medicine. 10 th
Oxford\: OUP; 2017.
894 p.
Johnston SL. Clinical Immunology. In\: Penman ID, Ralston SH, Strachan MWJ, Hobson RP, editors. Davidson’s Principles and
Practice of Medicine. 24 th
London\: Elsevier; 2023. p.59-86.

Image references

Figure 1. Wiremu Stadtwald Demchick. K i d n e y l o c a t i o n a f t e r t r a n s p l a n t a t i o n . License\: [CC BY]
Figure 2. Rmarlin. K i d n e y f o r t r a n s p l a n t f r o m l i v e d o n o r . License\: [CC BY-SA]

Reviewer

Miss Emily Thompson
NIHR Clinical Lecturer in Transplant Surgery

Acute Kidney Injury (AKI)
Chronic Kidney Disease (CKD)
Glomerular Disease (Glomerulonephropathies)
Haemodialysis
Henoch-Schönlein Purpura (IgA Vasculitis)
Source\: geekymedics.com
https\://app.geekymedics.com/notebook/2863/ 8/8