Renal transplantation Flashcards
What happens to the non-functioning kidneys in renal transplant?
Nothing - leave them where they are
Where is a kidney transplant placed?
Right iliac fossa
Which vessels are kidney transplants anastomosed onto?
External iliac artery and vein
Ureter
What needs to be compatible with regard to transplants?
Blood group
Human leucocyte antigen matching (tissue typing)
What is blood group compatibility?
Blood antigens must match as antibodies for the other blood antigens are found within the blood
Which blood group does not have an antibody against it?
O
What are human leucocyte antigens?
Cell surface proteins which activate the immune system when foreign antibodies bind
What are the 3 important types of HLA with respect to transplantation?
HLA DR
HLA A
HLA B
(Dr Ab)
With respect to each HLA A, B & DR there are two antigen subtypes. Why is this?
Each parent passes on one subtype to their offspring
Why is HLA relevant?
If a patient has been exposed to their donors HLA antigen before they might have developed an antibody against it and this will therefore cause tissue rejection
A more closely matched kidney is associated with improved survival length of the transplant. T/F
True
How might a patient be exposed to other HLA antibodies?
Blood transfusions
Pregnancy (placental maternal blood flow)
Previous transplants
Reduced cold ischaemic time is associated with better transplant survival. T/F
True
Explain transplant rejection
HLA antigen binds to dendritic cells –>
Antigen presenting cells express antigen on MHC complex –>
Helper T cells are activated –>
Increase B cell efficiency ; complement pathway activation ; increase in NK cells and cytotoxic T cells –>
Antibody production ; Direct cell killing –>
Rejection
What is the difference between cellular rejection and antibody mediated rejection?
Cellular rejection - NK cells and CD8 cells
Antibody mediated - B cells
Immunosuppression increases the risk of what?
Infection
Malignancy
Which infections are immunosuppressed patients prone to?
CMV (herpes group)
Pneumocystitis jirovecii
Recurrent UTI
BK virus
Which malignancies are immunosuppressed patients prone to?
Non melanoma skin cancer (SCC)
Post transplant lymphoma
Why is CMV important in terms of transplant immunology?
Giving a patient not infected with CMV a CMV infected kidney is bad news unless you give antivirals (valganciclovir)
How is pneumocystis jirovecii treated?
Co-tramoxazole
EBV post-transplant increases risk of what?
Lymphoma
How is post transplant lymphoma treated?
Reduction in immunosuppression + anti cancer agents
What biochemical marker might help to warn of kidney transplant rejection?
Serum creatinine
Which cells must be repressed post-transplantation?
T helper cells
B cells
Hence complement & cytokines
List the types of transplant rejection
Hyperacute
Acute
Chronic
What causes hyperacute transplant rejection? How long does it take to occur? How is it managed?
Preformed antibodies to transplant antigens
Minutes
Transplant removal
How is acute transplant rejection caused? How is it managed?
T cells or B cells
Early
Increased immunosuppression (+ steroids in short term)
How is chronic transplant rejection caused? How is it managed?
Immunological and vascular deterioration
Unsure how to treat
Describe how transplant patients are immunosuppressed
Induction - high dose steroids, MMF, cyclosporin, tacrolimus, antibodies
Consolidation - lowered doses
Maintenance - balanced low doses
Name two calcineurin inhibitors
Cyclosporin
Tacrolimus
How do calcineurin inhibitors work?
Reduce NK and CD8 cell activation and thus decrease cytokine release (preventing B cell proliferation and antibody production)
What are the side effects of calcineurin inhibitors?
Renal dysfunction
Hypertension
Diabetes (in at risk populations)
Tremors
Which organ are calcineurin inhibitors metabolised by? Why is this relevant?
Liver
The specific liver pathway that metabolises calcineurin inhibitors also metabolises lots of other drugs hence drug interactions can be an issue
How do azathioprine and mycophenolate work?
Block purine synthesis thereby suppressing the proliferation of lymphocytes and B cells
What are the side effects of azathioprine and mycophenolate?
Leucopaenia
Anaemia
GI disturbance
Which drug should you not give azathioprine with?
Allopurinol
How do steroids work with regards to immunosuppression?
Non selective suppression of T cells and B cells
What are the side effects of steroids?
Osteoporosis
Weight gain
Infection
Diabetes
What types of kidney donation exist?
Deceased brain dead
Deceased cardiac death
Live donor
Kidney pancreas
Which type of diabetes patients are suitable for pancreas transplantations?
Type 1 diabetics with renal failure
What is the criteria for a patient to be eligible for transplant?
Life expectancy >5 yr
No cadaveric transplant if >6 months prior to starting haemodialysis
Tissue type match (person who has been on list longest gets organ)
How must transplant patients be assessed?
CVS risk (ECG, cholesterol, ETT +/- angiogram, echo) Virology (hepatitis, HIV, CMV, EBV) Chest x-ray Bladder assessment Investigation of co-morbidity
Which viruses should be treated prior to transplant?
Hep B
Hep C
HIV
What are the absolute contraindications to transplant?
Untreated malignancy Untreated TB Severe IHD Severe airways disease Active vasculitis Severe peripheral vascular disease
How is a live donor assessed?
ECG Chest x-ray Virology GFR (direct measure) Proteinurea quantification 24hr blood pressure Renal angiogram X-match against recipient
What might a renal transplant scar look like?
Like appendix scar but bigger and with underlying mass
What are the complications of transplant?
Haemorrhage
Stenosis/thrombosis
Ureteric stricture and hydronephrosis
Wound infection
Why do post transplant patients get a central line?
To measure central venous pressure
How will delayed graft function present? How is it treated?
Post transplant acute tubular necrosis
Haemodialysis until begins to work within 10-30 days
