ASN QBank Pearls - Renal Transplant Flashcards
what are HLA class 1?
- A, B, C
- all nucleated cells
what are HLA class 2?
- DP, PQ, DR
- on Ag presenting cells (APCs)
sensitization of immune system occurs from
- blood transfusions
- pregnancy
- prior transplants
panel reactive antibodies (PRA)
- tells how sensitized a patient is to HLAs in general population
- 0-100%
donor specific antibodies (DSA)
- tests presence of Abs to DONOR’S HLA types only
- semiquantitative
crossmatch
- combines donor cells w/ recipient serum
positive crossmatch predicts what?
HYPERacute rejection
blood groups between donor and recipient must be
compatible (like blood transfusion)
crossmatch between donor and recipient must be
negative
HLA typing of donor and recipient determines
- matching compatibility
- range from 0/6 to 6/6
HLA matching has better outcomes if
match is 6/6
can rejection still occur if HLA match is 6/6? and, if yes, why?
- yes!
- non-HLA incompatibilities
contraindications to kidney transplantation
- poor cardiac function
- morbid obesity
- psychosocial issues which can affect compliance
- active infection
- recent, unresolved cancer
- ANY serious comorbidity which reduces life expectancy
infections that need to be tested for in a transplant recipient
- HBV
- HCV
- EBV
- CMV
- syphilis
- HIV
- latent TB
what cancer screening needs to done for transplant recipients?
- mammogram
- PAP smear
- PSA
- colonoscopy
waiting time after cancer treatment for most cancers before proceeding w/ transplant?
2 years
waiting time after cancer treatment for metastatic breast, colorectal, and melanoma before proceeding w/ transplant?
5 years
waiting time after cancer treatment for non-melanoma skin cancer and some in situ malignancies before proceeding w/ transplant?
none, considered low risk
contraindications to living donation
- age < 18
- GFR < 80 ml/min
- hematuria
- proteinuria
- HTN
- DM
- obesity
- h/o cancer
- infectious disease
- significant, unresolved medical issues
- psychosocial factors
- inability to give informed consent
long term risk of ESRD over 15 years for kidney donor
6 fold increase
donor evaluation
- H&P
- CMP
- FLP
- GFR; 24 hour urine
- UA, C+S
- serum hCG
- EKG
- CXR
- TTE
- age-appropriate cancer screening
- CT a/p
- SW evaluation
minimum criteria for listing for kidney transplant
- initiation of dialysis (time is backlogged from start time)
- GFR < 20 ml/min (time starts at time of eval and consent given to list)
what is a non standard kidney?
- higher kidney donor profile index (KDPI) score (higher = worse)
- cardiac death donor (longer CIT)
- “higher-risk” donors
- HBV and/or HCV donors
thymoglobulin MOA
depletes T cells
basiliximab MOA
blocks IL-2 receptors in T cells
thymoglobulin adverse effects
- leukopenia
- thrombocytopenia
- fever
- flu-like symptoms
CNI MOA
binds FK-binding protein thus inhibiting response to IL-2
CNI adverse effects
- Afferent arteriole vasoconstriction
- hyperkalemia
- metabolic acidosis
- hypomagnesemia
- hyperglycemia and HLD by blocking beta cells in pancreas
- renal fibrosis (long-term)
azathioprine and MMF adverse effects
- leukopenia
- MMF can cause diarrhea
do levels of azathioprine and MMF correlate well with toxicity?
no
use of azathioprine and allopurinol is
contraindicated
sirolimus MOA
mTOR inhibitor; mTOR is protein kinase that regulates cell growth and survival. Sirolimus- binds FK-binding protein thus inhibiting IL-2 response (prevents t cell and bcell activation and proliferation)
adverse effect of sirolimus
- poor wound healing
- proteinuria
Leukopenia/anemia/low plts
Interstitial pneumonitis
Edema
belatacept MOA
blocks accessory pathway of T cell stimulation
advantage of using belatacept
avoid CNI nephrotoxicity
perioperative complications
- wound infection
- bleeding
- lymphocele
- urine leak
- transplant RAS
delayed graft function (DGF) histology
ATN
delayed graft function (DGF) risk factors
- quality of donor kidney
- kidney from after cardiac death donor
- prolonged CIT
- perioperative hypotension
how long to wait before renal transplant biopsy if DGF?
4 weeks
opportunistic infections
- first month
bacterial, perioperative
opportunistic infections
- 2-6 months
viral;
- CMV
- BK (polyoma) virus
opportunistic infections
- > 6 months
mostly bacterial
infection ppx
- antifungal
- fluconazole or nystatin x 1 month
infection ppx
- PJP
- SMX/TMP or dapsone (if sulfa allergy) x 12 months
infection ppx
- CMV
depends on IgG serology
infection ppx
- CMV positive donor
- CMV negative recipient
valganciclovir x 6 months
infection ppx
- CMV positive donor
- CMV positive recipient
valganciclovir x 3 months
infection ppx
- CMV negative donor
- CMV negative recipient
low risk
CMV clinical manifestations
- flu-like symptoms
- leukopenia
- diarrhea
- colitis
- rare; hepatitis, pneumonitis, ophthalmitis
BK virus normally dormant in
urinary tract
subacute or chronic loss of allograft function d/t over IS
BK nephropathy
treatment for BK nephropathy
taper down IS
uncommon clinical features of BK virus
- hematuria
- ureteral stricture
ddx of AKI in setting of transplant
- same ddx as native kidneys (prerenal, renal, postrenal)
- acute rejection
- CNI toxicity
- surgical complications (if soon after surgery) (urine leak, ureteral stenosis, transplant RAS)
acute cellular rejection (ACR) histological findings
(in order of worsening severity)
- T cell infiltrates
- tubulitis
- cellular involvement of larger blood vessels
- hemorrhage
antibody mediated rejection (AMR) histological findings
(in order of worsening severity)
- PERItubular capillaritis
- staining for C4d
- duplication of endothelial BMs
- positive DSA
ACR treatment
- pulse steroids
- thymoglobulin if more severe
AMR treatment
- plasmapheresis
- IVIG
- rituximab
treatment response to ACR
aggressive presentation, but may respond well
treatment response to AMR
often insidious onset and poor response if caught late
preformed DSA, although very rare, can lead to
hyperacute rejection
which type of rejection has better outcome?
ACR
MC type of cancer post-transplant
squamous cell skin cancer
rare cancer caused by EBV post-transplant
post-transplant lymphoproliferative disorder (PTLD)
post-transplant lymphoproliferative disorder (PTLD) risk factors
- EBV negative recipients
- greater intensity and duration IS
treatment for post-transplant lymphoproliferative disorder (PTLD)
- taper IS as tolerated
- heme/onc
MCC of death w/ functional graft
CVD
CNIs inhibit metabolism of statins which leads to increased risk of
rhabdomyolysis
vaccines to AVOID post-transplant
- avoid LIVE vaccines
- varicella
- INHALED influenza
- MMR
- meningococcal
vaccines that should be received post-transplant
- INJECTABLE influenza
- pneumococcal
recurrence uncommon, but can be severe immediately post-transplant
FSGS
treatment for FSGS that occurs post-transplant
plasmapheresis
does HPT improve after transplant?
yes, partially
does fracture risk improve after transplant?
no
does fracture risk improve post-transplant if steroids are tapered off?
no, they are still at increased risk compared to general population
is infertility reversed after kidney transplant?
yes; should use contraception if not planning on conceiving
risks to mother in pregnancy after transplantation
- rejection
- preeclampsia
risks to fetus in post-transplant mother
- fetal loss
- low birth weight
- teratogens (MMF and sirolimus; must be stopped before pregnancy)
- infection; CMV
indication for pancreas transplant
hypoglycemic transplant
- usually occurs after rapid d/c’ing of IS
- fatigue
- fever
- gross hematuria
- allograft tenderness
graft intolerance syndrome
treatment of graft intolerance syndrome
restart IS w/ higher dose steroids
patients with bladder-drained pancreata develop
metabolic acidosis (loss of bicarb into bladder)
immunohistochemistry positive for SV40 (looks brown)
BK nephropathy
second line treatment for BK nephropathy after reduction of IS
- IVIG
- or leflunomide or cidofovir
treatment for post-transplant erythrocytosis (PTE) (hb > 17 g/dl, hct > 51%)
ACEI
which medication group can improve nephrotoxic effects of cyclosporine?
CCBs
biggest risk factor for post-transplant lymphoproliferative d/o with belatacept
EBV negative recipient
sirolimus induced proteinuria will likely show up on biopsy as
podocytopathy causing FSGS
ABO incompatible transplant is a/w
significantly higher risk of infection and hemorrhagic complications
highest rate of recurrence post-transplant
diabetic nephropathy (40%)
second highest rate of recurrence post-transplant
FSGS (20-30%)
- one of the MCC of allograft failure in early post-transplant period
- sudden anuria
- tenderness around allograft
early graft thrombosis
HF before surgery with UF > 1.5-2 kg may be a strong predictor of
intraoperative hypotension
- progressively worsening HTN
- unresponsive to meds
- worsening renal function
- recurrent flash pulmonary edema
transplant renal artery stenosis (TRAS)
transplant renal artery stenosis (TRAS) treatment
angiographic stenting
IS medication that causes alopecia
tacrolimus
IS medication that causes hair growth and hirsutism
cyclosporine
how to diagnose CMV in a post-transplant patient with symptoms
serum CMV PCR
does SLK have lower immunological risk for kidney rejection?
yes
medication used in treatment of resistant hypomagnesemia
amiloride
treatment for lymphocele
laparoscopic peritoneal window creation
brown crap on immunohistochemistry in setting of AMR
C4D positivity
management of major surgery in post-transplant patient on sirolimus for IS
- hold sirolimus x 5-10 days before surgery (wound healing)
- add steroids if not already on any
on histology, BK nephropathy mimics
ACR
difference in nephrotoxicity between tacrolimus and cyclosporine
same, but tacrolimus is less nephrotoxic at lower doses
what solution is infused during plasmapheresis? and is a possible adverse effect?
- citrate for AC
- hypocalcemia
expected post transplant survival (EPTS) score is based on which 4 factors?
- age
- DM
- time on dialysis
- previous solid organ transplant status
what factors are a/w increased risk of PTLD?
- recipient EBV negative
- number of HLA mismatches (especially HLA-B or HLA-DR)
is BK shedding in urine (BK viruria) common?
yes, about 30%
donor risk of ESRD post-nephrectomy
8-10 fold increase
compensatory hypertrophy post-nephrectomy returns GFR to
75% of baseline at long-term f/u
BK nephropathy initial test for diagnosis
serum BK PCR
is weight or body fat composition different at 1 year in patients on steroids vs steroid-avoidance protocols?
no
acute cellular rejection types
- 4 cells infiltrated per tubule AND TUBULITIS
type 1
acute cellular rejection types
- > 10 cells infiltrated per tubule AND ENDOTHELIALITIS
type 2
acute cellular rejection types
- lymphocytic cell infiltration AND interstitial hemorrhage
- vasculitis
- fibrinoid changes
type 3
T cell activation cascade signals
- which medications block signal 1?
- thymoglobulin
- alemtuzumab
- tacrolimus
- cyclosporine
T cell activation cascade signals
- which medications block signal 2?
belatacept
T cell activation cascade signals
- which medications block signal 3?
- basiliximab
- sirolimus
- everolimus
- MMF
- azathioprine
- leflunomide
treatment of ACR typically involves increasing which T cell activation cascade signal blockers?
signal 1 and 3
medications that increase CSA levels (cyclosporine toxicity)
# abx - macrolides # CCB - verapamil - diltiazem # mTOR inhibitors - sirolimus - everolimus #antifungals - ketoconazole - fluconazole
what is the MOST appropriate INDUCTION IS?
- Caucasian recipients of two-haplotype-identical, living, related allograft
no induction required (low risk for rejection)
what is the MOST appropriate INDUCTION IS?
- second transplant
- sensitized recipients
- transplant across ABO blood type
antithymocyte globulin (ATG)
what is the MOST appropriate INDUCTION IS?
- first line agent
basiliximab
MMF MOA
inhibits inosine monophosphate dehydrogenase (IMPD), a key enzyme in purine synthesis
azathioprine MOA
- inhibits both DNA and RNA synthesis
- also suppresses purine synthesis
- action on cell cycle is not precisely defined
which IS in a KTR should be avoided to prevent lowering sperm count?
mTOR inhibitors
MCC of anemia is a post-renal transplant patient
poor graft function
histopathological finding that is an independent risk factor for anemia in a post-renal transplant patient
IFTA from prolonged CIT
MOST strongly a/w new onset DM after kidney transplantation (NODAT)?
advanced recipient age
relative risk of malignancy post-renal transplant
- NHL
40-50%
relative risk of malignancy post-renal transplant
- Kaposi’s sarcoma
400-500%
relative risk of malignancy post-renal transplant
- SCC
15-20%
relative risk of malignancy post-renal transplant
- melanoma
8-10%
relative risk of malignancy post-renal transplant
- Ca of vulva/anus
100%
highest ABSOLUTE risk of malignancy post-renal transplant
SCC
BK polyoma viral infection progression is characterized by what stages?
urinary decoy cells –> viruria –> viremia –> BK nephropathy
