kidney transplantation Flashcards
types of transplant
- deceased heart beatingdonors (brain stem death)
- nonheart beating donors
- live donation (altruistic)
directed and undirected
paired donation
financially procured (illegal in most countries)
assessing potential recipients
- reasonable life expectancy (>5yrs)
- make sure patient able to undergo anaesthetic, procedure, immunsuppression, post-op
(takes about 3months until after 3months)
things assessed:
- immunology – tissue typing & antibody screening
- virology (exclude active infection)
HBV, HCV, HIV, EBV, CMV, VZV, Toxo, Syphilis - cardioresp risk ECG, Echo +/- ETT, Coronary angio CXR, +/- PFT, CPEX
- periph vessels
- bladder function
- mental state
- any co-morbidity/PMHx which may influence transplant or be exacerbated by immunosuppression
- independent assessment
contrainds
- malignancy
(known untreated malignancy
solid tumour in last 2-5 years) - active infection
- severe IHD, not amenable to surgery
- severe airways disease
- active vasculitis
- severe PVD (unusable vessels)
- hostile bladder
assessing live donors
- physical fitness
- they fine after 1 kid? isotope GFR
- normal anatomy kidneys
- co morbs (hypertension, proteinuria, haematuria)
- immunological compatible
- psych compat?
- no coercion?
***tissue typing
blood group
HLA (major histocompatibility complex MHC)
impmortance of hla mathcing
w/o immuno supp - critical!!
if immunosup then better graft survival
sensitisation to subsequent transplants
sensitising events other than transplantation
- blood transfusion
- pregnancy or miscarriage
- previous transplant
- lead to formation of antibodies to non-self antigens
- ? how to overcome immunological barriers in living donation
paired donation or altruistic donation
desensitisation
- active removal of blood group or donor specific HLA antibody
- pre-transplant antibody depletion
plasma exchange
B cell antibody (rituximab) - monitor antibody levels and transplant when below acceptable threshold
- associated with greater immunosuppression and higher rejection rates.
transplant procedure itself
- extra peritoneal procedure
- transplant inserted in iliac fossa
(attached to external iliac arterty & vein
ureter plumbed into bladder with stent) - wound ~15-20cm long
- average 2-3 hour operation
- 7-10 days in hospital
- regular clinic follow up
- usually back to full activities & work in 3 months
surgical complications of kidney transplant
- bleeding
- arterial stenosis
- venous stenosis / kinking
- ureteric stricture & hydronephrosis or leak
- wound infection/dehiscence
- lymphocele
signs that tranplant working
- immediate graft function
- good urine output
- falling urea & creatinine - delayed graft function
- post-transplant ATN
- often need HD in interim
- usually works within 10-30days
- usually need biopsy (difficult to detect rejection) - primary non function
- transplant never works and is explanted
types of rejection
- hyperacute rejection
- due to preformed antibodies
- unsalvageable
- transplant nephrectomy required - acute rejection
- cellular or antibody mediated
- can be treated with increased immunosupression - chronic rejection
- antibody mediated slowly progressive decline in renal function. Poorly responsive to treatment.
what is anti-rejection therapy and its ideal treatment
reduces activation of T cells
aim is to prevent host V transplant mediated immune response
ideal treatment:
- specific
- few side effects
- able to monitor its effect on immune system
- actual treatment is not ideal
immunosuppressive therapy
- Induction Treatment
Basiliximab/Dacluzimab
Prednisolone iv during operation - Maintainance Treatment
Prednisolone, tacrolimus, MMF
Prednisolone, ciclosporin, azathioprine - Acute anti-rejection Treatments
Pulsed iv methylprednisolone (ACR)
Anti-thymocyte globulin (ATG), (resistant ACR and AMR))
IV Immunoglobulin (AMR)
Plasma exchange (AMR)
Rituximab, Bortezimab, Eculizumab (AMR)
& intensification of immunosupression
infections due immunosuppresion
bacterial infection (common)
- UTI
- LRTI
give prophylaxis for PJP
viral infections
CMV, HSV, BK
fungal infections (rare)
CMV
associated w/ early graft loss
Common if recipient not immune but donor has previous infection.
causes
renal & hepatic dysfunction
Oesophagitis, Pneumonitis & Colitis
Increased risk of rejection
evidence
IgM + & PCR +
treatment
Prophylactic PO valganciclovir in higher risk patients
IV ganciclovir if evidence of infection
BK nephropathy
- prevalent and indolent in uroepithelium
- reflection of over immunosuppression
- can mimic rejection
- no effective anti-viral therapy
- treat by reducing immunotherapy
- monitor blood viral load by PCR
commonest cancers in immunosupp I think
non-melanoma skin cancers
lymphoma (e.g. EBV mediated PTLD)
solid organs
what is post transplant lymphoproliferative disease (ptld)
- occurs in all forms of transplantation in all forms on transplantation
- depends on level of immunosuppresion
- usually related to EBV infection
post transplant lymphoproliferative disease (ptld) treatment options
reduce immunosuppression
(easier in renal transplant than in heart)
chemotherapy
no role for antiviral therapy
long term follow up (usuals)
compliance
rejection
hypertension assessment of CVS risk
chronic graft dysfunction
UTI
recurrent primary renal disease
surveillance for malignancy
viral mediated graft dysfunction
management of CKD
causes of graft loss
acute rejection
death w/ a functioning graft
recurrent disease
chronic rejection
viral nephropathy
PTLD
relevance of induction monoclonal antibodies
basiliximab or dacluzimab
block il-2 receptor on CD4 T-calle
prevent activation of these cells therefore prevent rejection
not useful if rejection has already started
how glucocorticoids are used and their side effecrs
inhibit lymphocyte proliferation, survival and activation
suppress cytokines
side effects: weight gain, diabetes, osteoporosis
e.g.gyzamples of calcineurin inhibitors and their side effects
tacrolimus & ciclosporin
act by inhibiting activation of t cells
prevent cytokine release
side effects: renal dysfunction, hypertension, diabetes, tremor
