Transplantation Flashcards
Where are transplanted kidneys usually placed?
Transplanted kidney is placed into the iliac fossa and anastomosed to the iliac vessels
What happens to native kidneys following transplantation?
Usually remain in situ
What indications are there for native nephrectomy?
Size
-Polycystic kidneys
Infections
-Chronic pyelonephritis
How are donor kidneys preserved?
- Cold storage solutions to minimise oedema and preserve integrity of tissues
- Buffer free radicals
What are the possible surgical complications?
Vascular complications
- Bleeding usually at anastomotic sites and perirenal haematomas which can be venous or arterial
- Arterial thrombosis
- Venous thrombosis
- Lymphocele
Ureteric
-Urine leak
Infection
What types of immunosuppressive agents are there?
- Corticosteroids
- Calcineurin inhibitors
- Anti-proliferatives
- mTOR inhibitors
- Costimulatory signal blockers
- Depleting agents
Give examples of calcineurin inhibitors.
- Tacrolimus
- Cyclosporin
Give examples of anti-proliferatives.
-Mycophenolate mofentil
Azathioprine
Give an example of an mTOR inhibitor
Sirolimus
Give an examples of a costimulatory signal blocker.
Belatacept
Give examples of depleting agents
- Basiliximab (anti CD25)
- Anti-thymocyte globulin (ATG)
- Rituximab (antiCD20)
What are the possible side effects of corticosteroids?
- Hypertension
- Hyperglycaemia
- Infection
- Bone loss
- GI bleeding
What are the possible side effects of tacrolimus?
- Hyperglycaemia
- AKI
- Tremor
What are the possible side effects of cyclosporin?
- Hirsutism
- Hypertension
- AKI
- Gout
What are the possible side effects of mycophenolate mofetil?
- Cytopenia
- GI upset
What are the possible side effects of sirolimus?
- Lipidogenic
- Diabetogenic
- Pneumonia
What are the possible side effects of belatacept?
- Infection
- Malignancy
What are the possible side effects of ATG?
- Infection
- PTLD
What immunosuppressive agent is used for induction?
Basiliximab
What immunosuppressive agents are used for maintenance?
Tacrolimuc + Mycophenolate + steroids
What immunosuppressive agent can be used if calcineurin inhibitors can’t be used?
Belatecept
What type of deceased donations are there?
Donation after brain death/ DBD
-Standard/extended criteria
Donation after cardiac death/DCD
-Standard/ extended criteria
What type of living donations are there?
Living related donor
Living unrelated donor
- Spousal
- Altruistic
- Pool/paired
What is the criteria for brain death donation?
- Coma, unresponsive to stimuli
- Apnoea off ventilator (with oxygenation) despite build up of CO2
- Absence of cephalic reflexes
- Body temperature above 34 C
- Absence of drug intoxication
What cephalic reflexes must be absent for brain death donation?
- Pupillary
- Oculocephalic
- Oculovestibular (caloric)
- Corneal
- Gag
- Purely spinal reflexes may be present
What is extended criteria?
- Donor aged > 60y
- Donor aged 50-59 + history of hypertension, death from cerbrovascular accident or terminal creatinine of >132µmol/L
Describe paired donation.
- Donor A is unable to donate to recipient A and donor B is unable to donate to recipient B
- Donor A donates to recipient B
- Donor B donates to recipient A
Describe pooled donation.
- Family/friends are unable to donate to individual
- They are a match for someone else
- They donate to in a domino effect so that everyone within the group receives or donates
- May include an altruistic donor
How does kidney function and survival compare to general population following transplant?
- Similar patient survival to general population.
- Lower rate of ESRD compared to general population.
- Compensatory increase in GFR of remaining kidney to 70% of pre-donation values
- Compensatory increase greater in younger donors.
- Older age and high BMI were associated with GFR of <60.
- Relatively short follow up time (12 years).
What are the possible complications following renal transplant?
- Rejection
- Cardiovascular
- infective
- Malignancy
What are the 2 types of rejection?
- Cell mediated
- Humoral (Ab mediated)
What are the possible cardiovascular complications following transplant?
- Underlying renal disease
- CRF
- Hypertension
- Hyperlipidaemia
- PT Diabetes
What types of infection is there risk of following transplan?
- Bacterial
- Viral
- Fungal
What types of malignancy are associated with transplant?
- Skin
- Lymphoma
- Solid cancers
What are the types of acute rejection?
- T cell mediated rejection (TCMR)
- Acute antibody mediated rejection (ABMR)
What are the stages of T cell mediated rejection (TCMR)?
- Tubulointerstitial (Banff I)
- Arteritis/endothelialitis (Banff II)
- Areterial fibrinoid necrosis (Banff III)
What are the stages of acute antibody mediated rejection (ABMR)?
- ATN-like (Banff I)
- Capillaries and or glomerular inflammation (Banff II)
- Arterial inflammation (Banff III)
Why might hyperacute rejection occur?
Pre-existing alloreactvity to donor
What inflammatory processes can occur in TCMR?
- Lymphocytic infiltrate
- Tubulitis
- Endarteritis
- Endothelialitis
What microvascular inflammation can occur in ABMR?
- Neutrophil infiltration
- Glomeruli
- Peritubular capillaries
What occurs in ABMR?
- Microvascular inflammation
- Donor specific antibodies
- Positive C4D
What endocrine condition can occur after transplantation?
New onset diabetes mellitus
What is the most important transplant related infection?
CMV
How many transplant patients are affected by CMV?
Around 8%
How is the recipient affected by CMV?
- Transmission from donor tissue
- Reactivation of latent virus
What is the prognosis of CMV if untreated?
High mortality and morbidity
What can CMV cause in transplant patients?
CMV viremia
Tissue invasive disease
- Pneumonitis
- Hepatitis
- Retinitis
- Gastroenteritis
- Colitis
- Nephritis
What polyomaviruses are transplant at risk of?
- BK virus
- JC virus
- Murine polyoma virus
- SV40
How can BK virus manifest following renal transplantation.?
- Ureteral stenosis
- Interstitial nephritis
- ESRF
How can BK virus manifest itself following bone marrow transplantation?
- Haemorrhagic cystitis
- Pneumonitis
- Hepatitis
How can BK virus manifest itself in AIDS?
- Nephritis
- ESRF
- Retinitis
- Meningoencephalitis
- Pneumonitis
What are the risk factors for BKAN?
- Intensity of immunosuppression
- Patient determinants
- Organ determinants
- Viral determinants
What patient determinants are risk factors for BKAN?
- Older age
- Male gender
- White ethnicity
- DM
- Negative BKV serostatus (paediatric recipients
What organ determinants are risk factors for BKAN?
- Graft injury
- HLA mismatches
- Ureteral stents
What viral determinants are risk factors for BKAN?
Changes of epitopes of viral capsid protein VP-1
What is the outcome of BKAN?
- Allograft dysfunction
- Loss of graft in 45-80%
What is the treatment for BKAN?
Reduce immunosuppression
Antiviral therapy
- Cidofovir +/-IBG
- Leflunomide
Give examples of the relative risks of malignancy after renal transplant.
2 Colon, lung, breast
3 Testicular, bladder
5 Melanoma, leukaemia, cervical
15 Renal
20 Non-melanoma skin, Kapasi sarcoma, Non-Hodgkin’s lymphoma
