renal transplant Flashcards
what is criteria for DCD
absence of circulation, not EKG silence
causes of graft failure after first yr - 5
chronic allograft nephropathy (scarring) 40%, death 30% (CVD), acute rejection 7%, noncompliance 3%, recurrence 2%
top 3 causes of ESRD leading to txp
glomerular disease (30%), DM (20%), HTN (20%)
major factors affecting long term outcome - 5
HLA match, rejection (acute/ chronic), prior failed txp, comorbidities, race
relative contraindications to txp - 6
active infection, malignancy (document cure), active ongoing renal disease (SLE), hyperoxaluria type 1, severe atherosclerosis with uncorrectable disease, social problems (non compliance, psych, morbid obesity)
problem with FSGS and transplant
25% recur leading to upto 65% graft failure
what is extended criteria
> 60 yo, OR > 50 yo with 2(cr > 1.5, HTN, CVA death)
where are HLA found
surface of NUCLEATED cells
what chromosome is HLA on
6
parts to class 1 HLA antigen
3 alpha and 1 b2microglobulin with 1 carboxy terminal through cell membrane
parts to class 2 HLA antigen
2 alpha, 2 beta, 2 carboxy
how does rejection happen
HLA molecules on surface shed into circulation, APC’s (host or donor) in LN’s present molecule to T cells, stimulates cytokine release, which then go to graft to damage
what is signal 1
APC’s (host or donor) in LN’s present MHC to T cells - difference in binding cleft between alpha subunits sends signal
what is the result of signal 1
STARTS cytokine production
what is signal 2
AKA costimulation. sets of receptors on APC bind to t-cell –> stimulation
what is signal 3
cytokine IL2 released by CD4 is most potent. Stimulates CD8 t cells to become cytotoxic and attack organ with HLA organ it was sensitized to
CD4 vs CD8 t cells
CD4 (helper) activate CD8 (killer) and b-cells, CD8 = cytotoxic via perforins
class 1 vs 2 HLA and CD4 vs 8 T cell
class 1 has binding site for CD8, class 2 for CD4
what types of cells mediate acute rejection
donor APC’s present MHC to recipient T cells immediately
what types of cells mediate chronic rejection
recipient APC re-packages MHC to recipient t-cell
what is costimulation
signal 1 and 2
significance of co-stimulation
nieve t-cells become anergic/ undergo apoptosis without signal 2
hyperacute timing
min - hrs
acute timing
d- yrs
chronic timing?
mo - yrs
hyperacute mediating factors
preformed ab’s (humoral)
acute mediating factors - 2
cellular/ humoral (ab’s) responses
chronic mediating factor - 3
cellular/humoral response/ viral
hyperacute rejection primary finding
intravascular coagulation/ hemorrhagic necrosis
acute rejection primary finding
tissue destruction
chronic rejection primary finding
obliterative fibrosis
vessel endothelium @ hyperacute rejection
ab’s attack walls of endothelium and disrupt vessel
prevention of hyperacute rejection
crossmatch to ID if recipient has circulating preformed ab’s to HLA molecules on donor
first step in diagnosing acute rejection
biopsy
acute rejection histology - 2
infiltrate of mononuclear cells and plasma cells in interstitum
effect of acute rejection on kidney
causes tubulitis –> overrides tubules
first line therapy of acute rejection
high dose steroids
second line therapy given when? For acute rejection
vascular rejection aka Banf grade 2 or 3
how can you identify antibody mediated acute rejection
antibodies on artery walls on biopsy.
what are second line therapies for acute rejection - 3
anti-t cell ab’s (OKT3), plasmapheresis (remove AB’s), IVIG (block ab’s)
how to treat antibody mediated acute rejection
second line therapies (OKT3, plasmapheresis, IVIG)
gross findings in chronic rejection
atrophy/ fibrosis - cortical atrophy, whiteish kidney (fibrosis)
histologic findings in chronic rejection - 4
- interstitial fibrosis / tubular atrophy, 2. vascular intimal hyperplasia, 3. arteriolar hyalinosis, 4. glomerulopathy (double countour GBM)
intimal arteritis of chronic allograft nephropathy histo findings
lumen occluded - intima inflamed and infiltrated by inflammatory cells - occluding lumen
2 types of chronic allograft nephropathy
antigen dependent and independent
what is antigen dependent CAN - 3
after episodes of acute rejection, re-transplantation (preformed ab’s), triggering HLA system
antigen independent CAN - 5
ischemia/reperfusion at txp, nephrotoxic drugs, viral, hyperlipidemia, HTN
how does combination antirejection therapy work
use combination drugs that work at different points in cell cycle -synergistic effect and can use lower doses overall to minimize toxicity
common maintenance cocktail
calceneurin inhibitor, antiproliferative agent, steroid –> tacrolimus, mycophenolic acid, prednisone
cyclosporine and tacrolimus - what class r they
calcineurin inhibitors
most common side effect of calceneurin inhib - 2
nephrotoxic and bone marrow toxic
role of calineurin in CD4 T cell activation
CD4 - MHC engagement + 2nd signal + CD3 = increased intracellular calcium –> calcineurin activation –> dephosphorylation of NFAT and transfer to nucleus –> t cell activation and IL2 production
calcineurin inhib MOA
blocks IL2 gene transcription, preventing T cell activaiton early on
calcineurin inhib side effects - 5
nephrotoxic, HTN, DM, cosmetic changes (hersutism, gingival hyperplasia), neurotoxic
what is C2 level
cyclosporin Area under the curve level 2 hrs after po dose
how to monitor tacrolimus level
trough
sirolimus class
mtor inhibitor
mtor side effects - 3
marrow toxic, hyperlipidemia, slow wound healing
OKT3 MOA
monoclonal ab blocking CD3 and t cell activation
thymoglobulin MOA
AB’s against multiple cell surface antigens = profound T cell activation for weeks
mycophenolate mofetil, azathioprine - what class?
antiproliferative or antimetabolites agents
antiproliferative agent common side effect
bone marrow supression
mycofenolate side effect - 1
GI toxicity, diarrhea
azathioprine side effect - 1
liver toxicity
what is carrel patch
take a piece of aorta and place onto iliac when multiple vessels
pediatric pt receiving adult kidney - where?
anastamosed to aorta/ivc
pediatric en bloc to adult - vascular anastamosis
pediatric aorta and ivc attached to iliac
initial workup of txp dysfunction (non-immune causes) - 4
eval volume status, r/o bladder ourlet obstruction, screen for infection (blood/urine), check calcineurin levels
def of transplant dysfxn
cr > 20% baseline
effect of large pelvic lymphocele
can compress illiacs –> leg edema, decreased flow to kidney, DVT
most common viral post txp infection
CMV in 10-20%
cmv prophylaxis
gancyclovir
CMV features- 5
happens at 42 days postop, affected organs: GIT, liver, glomerulopathy, retinitis
BK virus sx - 5
rising cr (BK nephropathy), hemorrhagic cystitis, ureteral stenosis, sterile pyuria (viuria)
BK virus mgmt
reduce immunosupression, stop mycophenolate, start lefunomide (pyrimidine synthesis inhibitor) and cidofovir
most common fungal infections - 2
candida and torulopsis
fungal prophylaxis
fluconazole
opportunistic infection and prophylaxis
pcp & bactrim
live donor exclusion - age - 2
< 18 (consent) or > 70 - anesthetic risk and poor kidney
live donor exclusion - BP
> 140/90 in blacks, 1 drug HTN in whites w/ no LVH in whites considered
live donor exclusion - kidney - 4
proteinuria > 200 F 250 M, GFR< 80, ADPKD, kidney stones (multiple or clinically active)
live donor exclusion - others - 5
DM, prior cancer, hypercoagulable, psychosocial stressor, very abnormal CT
which kidney to remove in donor -4
single renal artery, left kidney (longer vein), smaller kidney, the one with abnormalities
general principal of donor nx
leave donor with better kidney
renal recovery in donor
under 50 yo have hypertrophy to final 65-75% total renal function
what is a pretransplant gu eval for recipient? - 4
sterile urine, VCUG if suspected abnormality, BPH - resect if not anuric
living vs cadaveric donor and success
poorly matched living is better than matched cadaveric
crossmatch: positive T cell/ class 1
no txp
who gets first transplant only - 3
pos T cell flow crossmatch only, negative T cell positive B cell, positive B cell flow
perioperative maneuvers that reduce impact of ischemia reperfusion - 5
hydration, mannitol, lasix, intra-arterial verapamil, low dose dopamine
which branching vessels can be tied off
small upper pole, not lower pole as may supply ureter
vascular thrombosis/leak mgmt
reoperate
urine leak/ureteral obstruction mgmt
endoscopic mgmt, or reoperation if endoscopy fails or necrosis
lymphocele presentation - 2
ureteral obstruction (rising cr), or iliac vein compression (leg edema/DVT)
lymphocele mgmt - 3
large and symptomatic require tx: percutaneous drainage, sclerosis, peritoneal window
ipp post TXP
considered safe
ureteral stents and transplant
higher risk of infection unless abx added
drug used to prevent and treat acute rejection
thymoglobulin
