QuestionSBA
QuestionChoice
This is incorrect because Hepatitis C would present with fever,  malaise, and jaundice, with other risk factors in the history such as transmission through blood, birth, or sexual intercourse. Note that Hepatitis C would also cause deranged LFTs, but CMV infection is more likely in this patient following a renal transplant.
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Hepatitis C
QuestionChoice
This is incorrect because VZV can cause shingles in the later years of life when a patient is immunosuppressed. This would present as a painful, vesicular, dermatomal rash which this patient does not have. VZV is also screened for prior to a renal transplant.
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d
Varicella Zoster Virus
QuestionChoice
This is incorrect because Hepatitis B would present with fever, malaise, and potentially jaundice, with other risk factors in the history such as transmission through blood, birth, or sexual intercourse. Note that acute Hepatitis B would also cause deranged LFTs with the AST and ALT possibly in the 1000s. However, CMV infection is more common in this patient following a renal transplant.
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Hepatitis B
QuestionChoice
This is correct because this patient has recently undergone a renal transplant. These patients are at risk of reactivation of latent CMV from within donor tissue within the first 6 weeks after a transplant secondary to immunosuppression. Note that a fever and deranged LFTs are key features for identifying CMV infection. It is managed with ganciclovir.
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a
Cytomegalovirus
QuestionChoice
This is incorrect because EBV would present with fever, lymphadenopathy and a sore throat. Hepatosplenomegaly may also be found on palpation. EBV infection in transplant patients typically occurs due to reactivation of latent EBV from donor tissue. It generally takes longer to present  (6 months+), and is often associated with post transplant lymphoproliferative disorder. As such, this case is too early post transplant to raise suspicion of an EBV mediated pathology.
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b
Epstein-Barr Virus
QuestionComment
thank you renal placement xxx
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Monoclonal Versicolor
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sees renal transplants, clicks cmv
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Ale
Concept
Chapter
# Summary

Renal transplantation is a form of renal replacement therapy (RRT) that may be offered to patients with end-stage renal disease (ESRD). Transplant is not suitable for all patients however long-term outcomes are better than other forms of RRT and quality of life is significantly improved. Donors are either living or deceased, with deceased donors being classified as either donation after circulatory death (DCD) or donation after brainstem death (DBD) donors. Thorough assessment and work-up is required prior to listing for transplant, with the patient's preferences and shared decision making central to the process. Lifelong immunosuppression is required following transplantation, which carries its own complications. Despite immunosuppression, transplants may be rejected in either the hyperacute, acute or chronic setting. Other complications include infection, thrombosis of the renal vein or artery and ureteric injury. 

# Definition

Renal transplantation refers to the surgical implantation of a healthy kidney from a donor (either living or deceased) into a patient with end-stage renal failure or progressive chronic kidney disease. It is one form of **renal replacement therapy**, with the other main type being dialysis. 

# Epidemiology

- Renal transplant is the most common solid organ transplant in the UK
- From 2023-2024 there were 3094 adult kidney only transplants performed in the UK
- 1142 were from DBD donors, 1115 from DCD donors and 837 from living donors
- There were 5779 adults on the active UK transplant waiting list on 31st March 2024
- There are significant inequalities in access to renal transplant
- People from South Asian and Black backgrounds typically wait 168-262 days longer than white patients to receive a transplant
- This is in part due to a shortage of donors from these communities
- The average age of a renal transplant recipient is 51 years
- More men than women receive renal transplants (reflecting the greater incidence of end-stage renal disease in men)

# Aetiology

Renal transplantation should be considered in patients with end-stage renal failure or chronic kidney disease (CKD) stage 4 with progressive disease - causes of these include:

- Diseases causing intrinsic kidney damage:
- Diabetes
- Hypertension
- Glomerulonephritis, which may be primary or secondary
- Conditions causing urinary tract obstruction:
- Recurrent urolithiasis
- Structural abnormalities (e.g. ureteropelvic junction obstruction)
- External compression (e.g. from a pelvic mass)
- Bladder voiding problems (e.g. benign prostatic hyperplasia, neurogenic bladder)
- Iatrogenic causes:
- Radiotherapy
- Nephrotoxic drugs, e.g. aminoglycosides, lithium, NSAIDs
- Renal involvement secondary to multisystem diseases
- HIV
- Myeloma
- Vasculitis
- Systemic lupus erythematosus (lupus nephritis)
- Amyloidosis
- Genetic kidney diseases
- Autosomal dominant polycystic kidney disease (ADPKD)
- Alport's syndrome
- Tuberous sclerosis
- Cystinosis
- Recurrent urinary tract infections
- Often secondary to vesico-ureteric reflux or other anatomical defects
- Leads to chronic pyelonephritis which may lead to end-stage renal disease

NB important **absolute contraindications** to renal transplantation include:

- Untreated malignancy
- Active infection (including untreated HIV)
- Active systemic vasculitis
- Life expectancy < 2 years for any reason
- Current IV drug abuse

# Classification

Renal transplants are categorised based on from whom the kidney has come from (i.e. the donor):

- **Live donors**
- May be related or unrelated, including non-directed altruistic donors (who do not know the recipient)
- Patients need to have compatible blood groups and HLA matching with the donor
- Donor-recipient pairs who are incompatible and so cannot directly donate are registered in the UK Living Kidney Sharing Scheme
- This allows either paired donation between two donor-recipient pairs, or a pooled donation where more than two pairs are involved
- Outcomes are best from live donors
- **Deceased donors**
- There are two main types - donors after brain death (DBD) and donors after circulatory death (DCD)
- Kidneys are retrieved from DBD patients whilst the heart is still beating, and after the heart has stopped in DCD patients
- The majority of DCD patients have had planned withdrawal of care (for example in intensive care)
- Long term outcomes are similar between DBD and DCD kidneys however delayed graft function is more common with DCD

# Investigations

Prior to being listed for a renal transplant, potential recipients need to undergo assessment of their fitness:

- Blood type (ABO) and tissue typing for HLA
- Crossmatch with donor to look for antibodies
- Baseline blood tests to ensure patients are optimised for surgery and to screen for undiagnosed comorbidities
- FBC, U&Es, LFTs, bone profile, clotting, lipids, HbA1c, parathyroid hormone
- Group and saves as for any surgery
- Assessment of cardiovascular risk
- All patients require a chest X-ray and ECG
- Higher risk patients (e.g. diabetes, older age) should also have an echocardiogram and cardiac stress test +/- angiography
- Testing for viral infections
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Varicella zoster virus (VZV)
- Hepatitis B and C
- HIV 
- Risk assess for tuberculosis 
- High risk patients (e.g. born in an endemic area) should be tested with an interferon gamma release assay (IGRA)
- Malignancy screening
- Ensure patients are up to date with national cancer screening (mammograms, cervical smear tests)
- Men over the age of 50 may be offered a PSA test (not part of a national screening programme)
- Patients with a heavy smoking history should be offered a CT chest to screen for occult lung cancer
- Cystoscopy should be considered for patients at high risk of bladder cancer (e.g. high-level cyclophosphamide exposure)
- Psychosocial assessment for all candidates 
- Specialist input (e.g. psychiatry, social work) may be required for patients at higher risk of poor outcomes, for example:
- Difficulties understanding the treatment process
- Lack of social support
- Neurocognitive difficulties
- Severe or poorly controlled mental illness
- Substance misuse or dependence
- Dental assessment to screen for dental and periodontal disease that may be an infection risk
- Patients with respiratory disease or symptoms should have lung function tests

# Management

**Conservative:**

- Ensure patients are well informed regarding their options for renal replacement therapy, including the option of conservative management
- Ensure patients have regular opportunities to re-discuss decision making around renal replacement therapy and their concerns and preferences
- After transplant, renal transplant recipients require lifelong follow-up with multidisciplinary team input
- Monitoring adherence to immunosuppressive treatment is crucial

**Medical:**

- All renal transplant recipients (apart from some transplants between identical twins) require lifelong immunosuppressive treatment
- Patients receive induction therapy for up to 2 weeks around the time of transplant - this is a more intensive immunosuppressive regimen
- For example, tacrolimus + mycophenolate mofetil (MMF) + steroids + basiliximab (an interleukin-2 receptor antagonist)
- Following this, lifelong maintenance therapy is commenced
- Triple therapy is standard, e.g. tacrolimus + MMF + low-dose steroids

**Surgical:**

- Offer a pre-emptive living donor transplant if available or listing for deceased donor transplantation
- During the transplant operation, a ureteric stent is usually placed to support the anastomosis of the bladder and ureter - this is removed around 6 weeks later
- In most cases the graft (donor kidney) is placed extraperitoneally in the right iliac fossa
- In most cases, the native kidneys are left in place 
- Nephrectomy of native kidneys (either before, during or after transplant) may be indicated e.g. in cases of recurrent pyelonephritis, or in autosomal dominant polycystic kidney disease if huge kidney size is a hindrance surgically

# Complications

## Immediate complications

- **Hyperacute rejection** may occur immediately after perfusion of the allograft intraoperatively, or in the following minutes to hours
- It is antibody mediated, e.g. due to ABO or HLA incompatibility
- The transplanted kidney will not function and needs to be removed
- Very rare in the UK due to pre-transplant cross-matching
- **Haemorrhage** which may be massive e.g. due to dissection of the renal artery anastomosis 
- **Ureteric injury** may require repeat surgical intervention - the ureteric-bladder anastomosis may also break down also causing intra-abdominal leakage of urine

## Early complications

- **Delayed graft function** is defined as a requirement for dialysis in the first week after transplant 
- It is a risk factor for graft rejection and decreased longevity of the graft
- Grafts with prolonged warm and/or cold ischaemia times are at increased risk 
- Warm ischaemia time refers to the time between the kidney being perfused by the donor to when it is perfused with preservation solution
- Cold ischaemia time refers to the time between the kidney being perfused with preservation solution to when it is re-perfused by the recipient's blood
- **Renal vein thrombosis** is a serious complication that leads to loss of the kidney in the majority of patients
- Patients present with refractory pain, reduced urine output, haematuria and deteriorating renal function
- Renal doppler ultrasound is first-line to confirm the diagnosis
- **Renal artery thrombosis** is rarer than renal vein thrombosis but also usually leads to graft loss
- Risk factors include hypercoagulable states, prolonged cold ischaemia time and hypovolaemia
- Patients present with sudden onset oliguria with pain and tenderness over the graft
- **Wound infection** is common especially as patients are on immunosuppressive treatment
- Other risk factors include diabetes, wound haematomas and urinary fistulas
- **Wound dehiscence** is not uncommon; patients are at increased risk due to poor wound healing because of prolonged uraemia and anaemia 
- Early, eg. bleeding, thrombosis, infection, urinary leak, lymphocele
- Late, eg. RAS, ureteric stenosis, bladder dysfunction
- **Acute graft rejection** usually occurs in the first few weeks or months after transplant
- Typically there is a T-cell mediated immune response against the graft
- A biopsy of the graft may be required for diagnosis
- IV methylprednisolone is usually first-line treatment, followed by escalation of immunosuppression

## Late complications

- **Chronic graft rejection** usually occurs at least a year after transplant
- It is characterised by a gradual deterioration in graft function, with interstitial fibrosis and tubular atrophy on biopsy
- **Infection** may mimic graft rejection, with patients at risk of opportunistic infections due to immunosuppression
- There is an increased risk of urinary tract infection in particular
- Patients may be given prophylactic antibiotics (e.g. co-trimoxazole for pneumocystis jirovecii) and antivirals (e.g. valganciclovir for cytomegalovirus)
- Cytomegalovirus (CMV) is the commonest opportunistic infection and manifests in a variety of ways including with fevers, cytopenias and gastrointestinal symptoms such as abdominal pain and diarrhoea
- Epstein-Barr virus (EBV) may reactivate, which may cause a glandular fever-like syndrome or posttransplant lymphoproliferative disorder
- BK virus is a type of polyomavirus that may reactivate due to immunosuppression and cause a nephropathy that can mimic acute rejection
- **Side effects of immunosuppressive medications**, for example:
- Corticosteroids: insomnia, weight gain, diabetes, hypertension, osteoporosis, Cushing syndrome, avascular necrosis of the hip
- Tacrolimus: impaired glucose tolerance, nephrotoxicity, peripheral neuropathy, alopecia, tremor
- Ciclosporin: nephrotoxicity, hirsutism, gingival hypertrophy, dyslipidemia
- Mycophenolate mofetil: gastrointestinal upset, leukopenia, photosensitivity
- Azathioprine: myelosuppression, pancreatitis, nausea
- **Malignancy** affects transplant recipients at higher rates than the general population
- Non-melanoma skin cancers are very common
- Other malignancies (e.g. renal cell carcinoma, lymphomas) are also seen more frequently
- Patients should undergo skin surveillance as well as national screening for cervical, breast and colorectal cancer

# Prognosis

- A kidney transplant from a deceased donor lasts on average 15-20 years
- A transplant from a living donor lasts 20-25 years
- However these are very variable, and 30-40% of grafts fail in the first 10 years after transplant
- Approximately 3% of grafts fail annually, with these patients having to go back on dialysis (and possibly be listed for another transplant)
- There is a significant survival benefit compared to dialysis 
- Good prognostic factors are younger age, shorter pre-transplant dialysis duration and absence of cardiovascular disease
- Poor prognostic factors include acute rejection, post-transplant infections and delayed graft function

# NICE Guidelines

[NICE - Renal replacement therapy and conservative management](https://www.nice.org.uk/guidance/ng107)

[NICE Technology Appraisal - Immunosuppressive therapy for kidney transplant in adults](https://www.nice.org.uk/guidance/ta481)

# References

[NHS Blood and Transplant - Annual Report on Kidney Transplantation 2023/2024](https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/34295/nhsbt-kidney-transplantation-report-2324.pdf)

[Kidney Research UK - Kidney Health Inequalities](https://kidneyresearchuk.org/wp-content/uploads/2019/09/Health_Inequalities_lay_report_FINAL_WEB_20190311.pdf)

[Patient UK - Renal Replacement Therapy and Transplantation](https://patient.info/doctor/renal-replacement-therapy-and-transplantation)

[Royal Free Hospital Kidney Transplants - Types of donors](https://www.royalfree.nhs.uk/services/kidney-services/kidney-transplants/types-donors)

[KDIGO Guideline on the Evaluation of Candidates for Kidney Transplantation](https://kdigo.org/wp-content/uploads/2018/08/KDIGO-Txp-Candidate-GL-FINAL.pdf)

[Chronic Kidney Disease, Dialysis, and Transplantation - Infection in Renal Transplant Recipients](https://pmc.ncbi.nlm.nih.gov/articles/PMC7152484/)

[British Transplantation Society - Post-Operative Care in the Kidney Transplant Recipient](https://ukkidney.org/sites/renal.org/files/FINAL-Post-Operative-Care-Guideline-1.pdf)
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Quesmed Tutorial: Infectious Diseases 
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Cytomegalovirus reactivation from latent infection of the donor organ is a common complication in renal transplant patients, often presenting with symptoms such as fever, fatigue, and abnormal liver function tests, and may lead to more severe systemic illness if not promptly managed.
A 49-year-old man presents to A&E with fever and myalgia. He denies any recent unwell contacts or coryzal symptoms. His past medical history includes chronic kidney disease stage 5, hypertension and a kidney transplant 6 weeks ago. On examination, he appears pale. He has a temperature of 38.5. His blood tests reveal deranged liver function.

Which of the following is the most likely causative organism?
a