Renal Transplant Flashcards
In end-stage renal failure, renal replacement therapies in the form of dialysis or renal transplant exist.
What is a transplant?
A tissue/organ taken from a person who has died or from a living donor and placed inside another person
What are the advantages of renal transplantation over dialysis? (6)
- Transplants mimic true renal function better than dialysis, as the transplanted kidney is operating 24/7 as a normal kidney should
- GFR is restored to ~50, compared to ~7 while on dialysis treatment
- Transplant offers the patient more freedom and so improves quality of life
- Survival is improved
- Financial benefit to patients as they can return to work
- Financial benefit to the NHS as dialysis is more expensive in the long run
What are the age restrictions for receiving a transplant?
There are none
However, co-morbidities often prevent transplant in elderly patients
What are the 3 types of donor that can give a transplant? Which is most common?
Decreased heart beating donors (most common)
Non-heart beating donors
Live donation
Describe each of the 3 types of transplant donor:
Decreased heart beating donors
Non-heart beating donors
Live donation
Decreased heart beating donors:
Patients on life support who have been confirmed as brain stem dead by two doctors, the organs are retrieved while the person’s heart is still beating
Non-heart beating donors:
An organ is retrieved from a person who is officially dead - as in their heart has stopped beating
Live donation:
A person who is still alive offers to have one of their organs removed and given to another
What is the difference between directed and undirected live donation?
Directed - the person wants to donate their organ to someone specifically e.g., a family member with ESRD
Undirected - the person wants to donate their organ but does not name or have an intended recipient to receive it
Number of kidney transplants being carried out has increased/decreased/stayed the same
Number of live donors offering kidneys has increased/decreased/stayed the same
Number of kidney transplants being carried out has increased
Number of live donors offering kidneys has stayed the same
What criteria must a patient/recipient meet to be considered for transplant?
- Life expectancy must be >5 years
- Must be fit enough to survive the operation and post-op period e.g., general anaesthetic, immunosuppression, post-op IV fluids etc.
- Must undergo an extensive assessment process
There is no survival benefit from transplantation until ? months after the transplant
3
What 8 investigations/assessments are carried out for the recipient before they can be considered for transplant?
- Immunology: tissue typing and antibody screening
- Virology (to check for previous or active infection)
- Assessment of cardiorespiratory risk e.g., ECG, Echo, Coronary angio, CXR, PFT
- Assess peripheral vessels (as blood will be shunted to the new kidney so ensure vessels are strong enough to still take blood to the legs)
- Assess bladder function
- Assess mental state (as transplant can exacerbate these)
- Assess any co-morbidity or PMHx which may affect the transplant or be exacerbated by immunosuppression
- Independent assessment by someone outwith the transplant team to ensure all the work-up has been performed adequately
List 8 contraindications to transplant
- Malignancy (current untreated or solid tumour in the past 2-5 years depending on grade)
- Active HCV/HIV infection
- Untreated TB
- Severe ischaemic heart disease, not amenable to surgery
- Severe airways disease
- Active vasculitis (should be suitable for transplant after a few months of treatment)
- Severe PVD (unusable vessels)
- Hostile bladder e.g., bladder outflow obstruction that will put back pressure on the new kidney
What criteria must a live donor meet to be considered as a donor? (7)
- Must be physically fit enough to cope with surgery and post-op period
- Must have adequate renal function to remain independent following nephrectomy
- Kidneys must be anatomically normal
- Should not have co-morbidities that will get worse with one kidney e.g., hypertension, proteinuria
- Should be immunologically compatible with the recipient
- Must be psychologically fit to donate e.g., able to cope with the recovery process
- Reasons for donating must be explored e.g., cannot be because they want to have a hold on/manipulate the recipient, cannot be because they have been coerced by someone else
Tissue typing must be carried out on the donor and recipient before transplant to reduce chance of organ rejection. What are the 2 types of tissue typing?
Blood group compatibility
HLA matching
What blood groups can a recipient have to be compatible with a donor with a blood group of... - O - A - B - AB ...?
- O: Any!
- A: A, AB
- B: B, AB
- AB: AB
What is HLA matching?
When recipients are matched with donors who have the same type of HLA (aka MHC) protein group found on antigen-presenting cells
What are the 3 main types of HLA group?
HLA-A, HLA-B, HLA-DR
Why is HLA matching important?
- There is a better chance of graft survival with immunosuppression
- Without immunosuppression, HLA matching is key to prevent rejection
Matching of which class of HLA (A, B or DR) is most important in renal transplantation?
HLA-DR as it is responsible for the most cases of acute graft loss
What is the top criteria for which recipient receives an available transplant?
A) Blood group compatibility
B) HLA matching
C) Time on the transplant list
Why?
B) HLA matching
This is because the organ is more likely to be rejected if there is a HLA mismatch. Once that organ has been rejected, subsequent transplants are more likely to be unsuccessful because the recipient now has antibodies formed against those particular foreign subtypes of HLA
List 3 sensitising events that can have lead to pre-formed antibodies which will attack non-self antigens in the transplant
Blood transfusion
Pregnancy or miscarriage
Previous transplant
With an undirected donated kidney, how is it decided who receives the organ?
- Any paediatric recipient is prioritised
- Then adult HLA match (i.e., 0, 0, 0 mismatch - HLA A, B, DR)
- Then 1, 0, 0 or 0, 1, 0 or 1, 1, 0 mismatch
- Then total HLA mismatch (this is when time on the waiting list comes into consideration)
In a directed kidney transplant, what are the two options if the paired donor and recipient are immunologically imcompatible?
- They can be involved in paired donation/ enter a paired donation pool
- The recipient can be desensitised
What is paired donation?
When an incompatible donor and recipient pair up with another incompatible donor and recipient where the donors will be able to swap recipients so that each receives a compatible organ
What is a paired donation pool?
- When multiple pairs of incompatible donors and recipients exchange donors until everyone finds a compatible match
- A non-directed donor is added to this pool to create a domino-effect
- The last kidney is given to a recipient on the transplant list
What is desensitisation?
Active removal of a blood group or donor-specific antibody from the recipient by plasmapheresis or a B cell depletor e.g., Rituximab
Is desensitisation effective?
Not completely
It is still associated with a greater need for immunosuppression and higher rates of rejection post-transplant
Describe the renal transplant procedure
- It is an extra-peritoneal procedure that takes ~2-3 hours
- An incision is made in the iliac fossa
- The donated kidney is grafted onto the external iliac artery and vein in the pelvis
- The donated kidney comes with a ureter which is grafted to the recipient bladder with a stent
- The native kidney is left in place more proximally
Describe the post-op period for the recipient
- 7-10 days spent in hospital
- Regular clinic follow up
- Ureteric stent removed after 1 month
- Usually back to full activities and work in 3 months
- They are left with a wound ~15-20cm in the iliac fossa
List 6 complications that may occur during renal transplant surgery
- Bleeding of anastomosis (explantation required)
- Arterial stenosis or thrombosis (explantation required)
- Venous stenosis/kinking or thrombosis (explantation required)
- Ureteric stricture and hydronephrosis (stent inserted at time of surgery to prevent this, then removed 1 month post-transplant)
- Wound infection/dehiscence (esp. in obese patients)
- Lymphocele (disrupted lymphatics leak and fluid can compress the ureter)
What are the 3 possible outcomes of renal transplant surgery?
Immediate graft function (good UO and falling urea and creatinine)
Delayed graft function
Primary non-function
What is the main cause of delayed graft function and how is it managed?
Post-transplant acute tubular necrosis caused by vascular interruption to the kidney while it is on ice between removal and transplantation
Patient usually requires dialysis for 10-30 days while the kidney recovers
What is primary non-function and how is it managed?
When the transplant never works
The kidney is explanted after ~1-2 months if there are still no signs of improved function
List the 3 types of transplant rejection
- Hyperacute rejection
- Acute rejection
- Chronic rejection
Describe the following:
- Hyperacute rejection
- Acute rejection
- Chronic rejection
- Hyperacute rejection:
Pre-formed antibodies attack the kidney within minutes to hours of transplant, this may be visible while still on the table as a blackening kidney, it is unsalvageable and must be removed, very rare now
- Acute rejection: T cell (most common) or antibody mediated rejection, occurs in ~15% of patients, can be treated by increasing immunosuppression
- Chronic rejection:
Antibody-mediated, slow progressive decline in renal function following transplant, poor response to treatment
What immunosuppressive therapies are given as…
- Induction therapy pre-transplant
- Maintenance treatment post-op
…?
Induction therapy pre-transplant:
- Basiliximab/Dacluzimab (IL-2 inhibitors to stop T cell activation)
- IV Prednisolone during the operation
Maintenance treatment post-op:
- Prednisolone + tacrolimus + MMF
What makes these drugs good immunosuppressors:
Prednisolone + tacrolimus + MMF
…?
Prednisolone: Inhibits lymphocyte proliferation, survival and activation, is a glucocorticoid
Tacrolimus: Inhibits T cell activation, is a. calcineurin inhibitor
MMF (mycophenolate mofetil): Suppresses proliferation of lymphocytes, is an anti-metabolite/anti-proliferative
Suggest an anti-rejection treatment for…
- Acute cellular rejection (ACR)
- Antibody-mediated rejection (AMR)
…?
ACR: Pulsed IV methylprednisolone
AMR: IV immunoglobulin
List 3 general complications of immunosuppressive therapy
- Bacterial infection (UTI and pneumonia most common)
- Viral infection (cytomegalovirus associated with early graft loss, BK viral infection has no anti-viral therapy so treat by reducing immunotherapy)
- Malignancy (non-melanoma skin cancers most common, lymphoma also common)
Why is lymphoma more common on immunosuppressive therapy?
It is usually related to EBV infection and referred to as post-transplant lymphoproliferative disease (PTLD)…
- EBV infection leads to polyclonal B cell proliferation
- When immunosuppressed, monoclonal B cell proliferation occurs
- This leads to lymphoma
What is the treatment for post-transplant lymphoproliferative disease (PTLD)?
- Reduce immunosuppression
- Chemotherapy (usually successful for remission)
(no role for anti-viral therapy)
During what time period do most graft losses occur?
In the first year after transplant
Due to rejection, infection, vascular problems etc.
What long-term follow-up is required post-transplant?
- Compliance with medication
- Renal function for rejection
- Hypertension and CV risk assessment
- Surveillance for malignancy
- Management of CKD (as all patients with a transplant are considered to have CKD)
Suggest 6 causes of graft loss
- Acute rejection
- Death (often due to CV burden)
- Recurrent disease
- Chronic allograft nephropathy (chronic rejection)
- Viral nephropathy
- Post-transplant lymphoproliferative disease (PTLD)
List 2 viral post-transplant complications and when they are most likely to occur
Cytomegalovirus (CMV): 4 weeks - 6 months post-transplant
Epstein-Barr Virus (EBV): aka post-transplant proliferative disease, occurs >6 months post-transplant + is associated w/ high dose immunosuppression
