Renal Transplantation Flashcards
What is a transplant?
Tissue taken from one person and placed in another = donor may be living or dead
Why must patients who receive a transplant started on immunosuppression?
The transplant is recognised as foreign by the immune system = must be suppressed to prevent rejection
What are some types of donors?
Decreased heart beating donors = brainstem death Non-heart beating donors Live donation (altruistic) = directed/undirected, paired donation, financially procured
What must be life expectancy of a patient be for them to be considered to receive a transplant?
> 5 years after transplant
How long does it take for a survival benefit from a transplant?
3 months after transplant
How are patients assessed before a transplant?
Immunology = tissue typing, antibody screening
Virology = HBV, HCV, HIV, EBV, VZV, syphilis
Assess CV risk = ECG, echo +/- ETT, angiogram, CXR
Assess peripheral vessels, bladder function, mental state and any co-morbidities
What are the contra-indications to getting a transplant?
Malignancy = known untreated cancer, solid tumour in last 2-5 years
Active HCV/HIV infection or untreated TB
Severe IHD, not amenable to surgery
Severe airways disease or peripheral vascular disease
Active vasculitis or hostile bladder
How are potential donors assessed?
Physical fitness for surgery and not being coerced
Anatomically normal kidneys
Enough renal function to remain independent after
Co-morbidities = hypertension, protein/haematuria
Immunologically compatible
What blood groups are compatible with each other?
Group O = all blood types
Group A = A and O
Group B = B and O
Group AB = O and AB
Why is HLA matching important?
Matching HLA is critical without immunosuppression and gives better graft survival with immunosuppression
What does HLA matching identify?
Sensitisation to subsequent transplants
What are sensitising events?
Lead to formation of pre-formed antibodies = blood transfusion, pregnancy/miscarriage, previous transplant
What is desensitisation?
Active removal of blood group or donor specific antibody = plasma exchange or B cell antibody (rituximab)
What kind of procedure is a transplant?
Extraperitoneal = wound usually 15-20cm long, operation lasts 2-3hrs
Where is the transplant inserted?
Iliac fossa = attached to external iliac artery and vein, ureter plumbed into bladder with stent
How long is the recovery from the operation?
7-10 days in hospital = usually back to normal activities and work in 3 months
What are some of the complications from surgery?
Bleeding, arterial stenosis, venous stenosis or kinking, ureteric stricture and hydronephrosis, wound infection, lymphocele
What are the outcomes after transplantation surgery?
Immediate graft function, delayed graft function or primary non-function
How can you tell if there is immediate graft function?
Good urine output, falling urea and creatine
What are some features of delayed graft function?
Post transplant ATN, often need haemodialysis in interim, usually need biopsy to exclude rejection, works within 10-30 days
What is the outcome of primary non-function?
Transplant never works
What are the types of transplant rejection?
Hyperacute, acute, chronic
What causes a hyperacute rejection?
Preformed antibodies = unsalvageable, transplant nephrectomy required
What causes acute rejection?
Cellular or antibody mediated = can be treated with increased immunosuppression
What causes chronic rejection?
Antibody mediated = slowly progressive decline in renal function, poorly responsive to treatment
What is the aim of anti-rejection therapy?
To reduce T cell activation
What is some of the immunotherapy given around the time of the operation?
Induction therapy = basiliximab, dacluzimab
IV prednisolone during operation
What are some immunosupressives that can be given as maintenance therapy?
Prednisolone, tacrolimus and MMF
Prednisolone, cyclosporin and azathioprine
What are some anti-rejection treatments?
Pulsed IV methylprednisolone (ACR)
Anti-thymocyte globulin (resistant ACR and AMR)
IV immunoglobulin (AMR)
Plasma exchange (AMR)
Rituximab, bortezimab, eculizumab (AMR) and intensification of immunosuppression
What are some features of the infections that transplant patients can get?
Side effect of suppression, give prophylaxis of PJP
Bacterial = common, UTI, LRTI
Viral = CMV, HSV, BK
Fungal
What is an important cause of morbidity in the first three months after a transplant?
CMV infection = associated with early graft loss, common if recipient isn’t immune but donor has evidence of previous infection
What can CMV infection cause?
Renal and hepatic dysfunction, oesophagitis, pneumonitis, colitis, increased risk of rejection
What evidence suggests CMV infection?
IgM and PCR positive
What is the treatment for CMV infection?
Prophylactic oral valangciclovir if high risk
IV ganciclovir if evidence of infection
Where is BK nephropathy common?
Prevalent and indolent in the uro-epithelium
What does BK nephropathy reflect?
Over-immunosuppression = can mimic rejection
How is BK nephropathy treated?
No effective anti-viral therapy = treat by reducing immunosuppression
Monitor blood viral load by PCR
What are some common malignancies linked with transplants?
Non-melanoma skin cancers, lymphoma, solid organs
What does post-transplant lymphoproliferative disease depend on?
Level of immunosuppression = can occur in all types of transplant
What is post-transplant lymphoproliferative disease usually related to?
EBV infection = causes polyclonal B cell proliferation then monoclonal proliferation, leads to lymphoma
How is post-transplant lymphoproliferative disease treated?
Reduce immunosuppression and give chemotherapy
No role for antiviral therapy
What are patients assessed for post-transplant?
Rejection, hypertension and CV risk, chronic allograft nephropathy, UTI, recurrent primary renal disease, malignancy, viral-mediated graft dysfunction, CKD
What are some causes of graft loss?
Acute rejection, death with functioning graft, recurrent disease, chronic allograft nephropathy, viral nephropathy, PTLD
What are some examples of induction monoclonal antibodies?
Basiliximab and dacluzimab = block IL-2 receptor on CD4+ T cells
What is the purpose of induction monoclonal antibodies?
Prevent activation of CD4+ T cells to prevent rejection = not useful if rejection has already started
What is the action of glucocorticoids?
Inhibit lymphocyte proliferation, survival and activation = suppress cytokines
What are some side effects of glucocorticoids?
Weight gain, diabetes, osteoporosis
What are some examples of calcineurin inhibitors?
Tacrolimus and cyclosporin = inhibit T cell activation to prevent cytokine release
What are some side effects of calcineurin inhibitors?
Renal dysfunction, hypertension, diabetes, tremor
What are some examples of anti-metabolites?
Azathioprine and mycophenolate mofetil (MMF)
What is the action of anti-metabolites?
Block purine synthesis = suppress lymphocyte proliferation
What are some side effects of anti-metabolites?
Leucopenia, GI upset, anaemia
