Kidney Transplantation Flashcards
Which kidney is preferred?
Anastamosis of vessels?
Left kidney b/c longer renal vein
Renal vein and artery anastamosis to recipient right external iliac vein and artery
donor ureter anastamose to recipient bladder
Warm ischemia vs. Cold ischemia
warm = time from cardiac death to cold = 60 min
cold = cold perfusion to recipient = 24-36 hrs
3 criteria for donor kidneys
1) Standard SCD = organs perfused until cross clamp
2) After death DCD = incr warm ischemia time and risk of delayed function
3) ECD = old patient or donor with PMHx assoc with 70% graft failure; for patients with high mortality on dialysis
MHC presentation
1) MHC = HLA bind peptide antigens
2) present to T cells via T cell receptor
Class 1 vs. Class II HLA
Class 1 = on all nucleated cells; presenting cytosolic peptides (viral) to CD8+
Class 2 = present on specific APC presenting to extracellular proteins (endocytosis) to CD4+
binding of HLA protein to antigen depends on :
1) amino acid structure of HLA protein
2) immunogenic epitope in antigenic peptide molecule
donor HLA antigens will be recog by recipient as ___ resulting in ___
“non-self” resulting in immune rejection unless recipient undergoes immunosuppression
What to look at for 6 HLA matches?
HLA-A
HLA-B
HLA-DR loci
HLA inheritance
1 set of HLA from each patient = co-dominantly expressed so 6 matches
Does HLA matching impact risk of acute rejection?
NOT IMPACT ACUTE REJECTION
decision to transplant not depend on HLA match but does affect level of immunosuppression after
what happens immunologically after transplanting kidney
1) recipient or donor antigen presenting cell presents foreign donor HLA molec
2) activates recipient T cell
3) after 2nd co-stim event, dephos of NFAT by calcineurin and IL-2 production
4) T cell prolif and clonal expansion
CD8+ T cells induce damage how
direct cytotoxicity
1) cell apoptosis
or
2) release cytotoxic proteins (FasL and granzyme B)
CD4+ T cells induce damage how
provide prolif signals for CD8+ T, B, macrophages –> APC
Triple therapy for kidney transplant recipient
1) calcineurin inhib
2) prolif signal inhib
3) prednisone
all immunosuppressive agents
side effects
incr risk of infection and cancer
Names of calcineurin inhib
Names of prolif inhib
1) cyclosporin
2) tacrolimus
1) mycophenolate mofetil inhibits purine synthesis
2) mTOR inhib inhib MTOR proliferation signlaing
Additional pre-renal AKI with transplant
1) volume depletion
2) transplanted renal artery/vein thrombosis = emergency
3) calcineurin effect on afferent arteriole
Additional post-renal AKI with transplant
1) transplant ureter obstruction from fluid collection (lymphocele, hematoma)
2) urine leak from breakdown of transplant ureter to bladder anastamosis, incr creatinine, require ureteral stent
Additional intra-renal AKI with transplant
1) recurrence of primary renal disease
2) infection (UTI, pyelo, CMV, BK virus)
3) T-cell or B cell rejection
treatment of CMV
treatment of BK virus
1) ganciclovir
2) reduction of immunosuppression
treatment of T cell rejection
treatment of B cell rejection
high doses steroids/T cell depletion with thymoglobulin
plasmapharesis and IVIG/rituximab
histology of T cell rejection
histology of B cell rejection
tubular + large vessel inflamm
small vessel + glomerular inflamm
complement damage
approach to kidney transplant AKI
1) n/diarrhea, volume status
2) US for post-renal
calcineurin inhib drug level
UA for infection/proteinuria
serum for BK or anti-HLA antibodies
3) renal transplant biopsy
