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
What is the criteria for initiating renal replacement therapy (RRT)?
GFR < 10mL/min + symptomatic
At what level of renal function should a patient meet with the transplantation team
GFR < 20ml/min
What are absolute contraindications to renal transplantation?
- Unable to adhere to medication regimen
- Active infection
- Active malignancy
- Mentally challenged
- Reversible cause of renal failure
- High probability of peri-operative mortality
- Anatomic issues (significant vascular disease)
What renal diseases have a high risk of recurring in the transplanted kidney?
- FSGS
- Hemolytic uremic syndrome
- Membranoproliferative glomerulonephritis
- Primary Oxalosis
What renal diseases have an intermediate risk of recurring in the transplanted kidney?
- Sickle cell
- Amyloidosis
- Fabry disease
- IGA nephropathy
- HTN nephropathy
- Diabetic Nephropathy
What renal diseases do NOT recur in a transplanted kidney?
- ADPCKD
- Cystinosis
- Renal dysplasia
- Alport syndrome (without anti-GBM antibodies)
How do you manage malignancy in transplant candidates?
Need to ensure disease cure, with disease free period dependent on type of CA. Oncology consults should be obtained to determine risk of recurrence, surveillance and long term prognosis. Patients should be screened for malignancy appropriate to age and gender
Melanoma - 5 years
Any metastatic malignancy - 5 years
High grade, invasive urothelial CA - 5 years
Any localized malignancy - 2 years
When is cholecystectomy advised prior to receiving a transplant?
- Gallbladder polyps greater than 1cm
2. Patients with diabetes and gallstones (increased morbidity in acute cholecystitis after transplantation)
What should a patient be assessed for prior to transplantation?
- Peripheral vascular system (claudication, past vascular procedures, femoral pulses) - if concerns doppler U/S or CT to assess
- Abdominal exam for surgical scars and information about past surgical history
What are the indications for a pre-transplant nephrectomy?
- Symptomatic renal stones not cleared by minimally invasive techniques or lithotripsy
- Polycystic kidneys that are symptomatic, extend below the iliac crest, have been infected or have solid tumors.
- Persistent anti-GBM antibody levels
- Significant proteinuria not controlled with medical nephrectomy or angioablation
- Recurrent pyelonephritis, or chronically infected kidney
- Grade 4 or 5 VUR with urinary tract infections
How should bladder outlet obstruction be managed in the transplant patient?
First line: medical management - alpha blockers and 5-alpha reductase inhibitors
Second line: TURP = should NOT be performed in anuric/oliguric patients as high risk contracture and strictures
Third line: CIC or indwelling catheterization
What are the guidelines for determination of neurologic death? (DND kidney)
- Complete cessation of all brain stem function (must be irreversible)
Determined by coma + absence of brainstem reflexes - Apnea challenge
Determined by no respiratory effort at PaCo2 60 or greater - Negative confirmatory tests if doubt exists.
What are the criteria for donation after circulatory death (DCD)?
- Donor does not meet neurologic death criteria, despite being comatose
- Decision made by family to withdraw cardio-pulmonary support.
- Death declared by absence of spontaneous respiration and sustained systole for 5 minutes.
What are the steps in the harvest of organs from a deceased donor?
- Median sternotomy and midline incision
- Organ inspection for signs of disease
- Vascular control - above and below organs for donation
- Cannulas inserted for the administration of preservation solution inserted into aorta, clamps are applied, venous effluent is vented and organs are flushed.
- Organs are extirpated.
- Immediately are cooled with slush once removed.
- Spleen and lymph node sections removed for histocompatibility.
How are kidneys preserved once extirpated?
- Hypothermia (4C) reduces energy expenditure
- Pulsatile preservation pumps may reduce vascular spasm
- Preservation solution (wisconsin solution) designed to maintain intracellular electrolyte composition
What are the contents of Wisconsin solution?
K lactobionate, KH2PO4, MgSO4, Raffinose, Adenosine, Insulin, glutathione, dexamethasone, allopurinol, penicillin, potassium, sodium
What are the four categories of kidney donors?
- Standard criteria donor younger than 35
- Standard criteria donor older than 35
- Expanded criteria donor
- Donation after circulatory death
What are the criteria of an expanded criteria donor?
- Age over 60
- Age between 50-59 with 2 or more of (death from stroke, HTN, elevated Cr just before organ recovery (1.5mg/dL)
*ECD has 80% 2 year graft survival versus 88% for SCD)
What happens in ABO incompatibility?
Acute rejection - antibodies bind to perceived antigen, trigger complement cascade, leading to coagulation, thrombosis and rapid graft loss.
What two classes of HLA’s are used in kidney allocation
HLA Class I (HLA-A, HLA-B, HLA-C)
- expressed by all nucleated cells through MHC
HLA Class II (HLA-DR, HLA-DQ, HLA-DP)
-Expressed by antigen presenting cells (dendritic cells, monocytes, macrophages, and B-lymphocytes)
What increases the risk of antibody and cellular rejection?
- Pregnancy
- Blood transfusion
- Prior transplantation
- Some infections
These things increase risk of forming HLA antibodies
individuals with antibodies directed at 20% of population are said to be sensitized
highly sensitized if antibodies directed at 80% of the population.
What are the three classes of renal rejection?
- Hyperacute - immediate (ABO incompatibility)
- Acute - 5 days after allogenic transplant (cellular +/- Ab bx to determine
- Chronic - gradual deterioration (vascular
What are contraindications to donation of a kidney?
- Renal disease (GFR < 80)
- Transmissible infection
- Active malignancy
- Mental disorder (incompetent)
- High operative risk
- Minor
- Anatomic unfeasibility
What are the indications for dialysis
- Acidosis (metabolic)
- Electrolytes (hyper-K)
- Intoxicants
- Volume overload
- Uremia (pericarditis, pericardial effusion)
What is the differential diagnosis of a fluid collection found post-operatively from a renal transplant
- Seroma
- Lymphocele
- Abscess
- Hematoma
- Urinoma
When should you intervene in a post-operative renal transplant fluid collection?
- Fever
- Pain
- Obstruction
- If may be contributing to decreased renal function
List causes of early graft dysfunction?
- ATN
- Calcineurin inhibitor toxicity
- Rejection
- Infection
- Obstruction
- Hyperglycemia
What is the definition of delayed graft function?
Requirement for dialysis during the first week of transplantation.
What are the classes of immunosuppressants and how do they work?
- Antiproliferative agents (azathioprine, and MMF) - Block DNA/RNA prodction
- Calcineurin inhibitors (cyclosporin and tacrolimus) - inhibit T-cell activation
- Monoclonal antibodies (Anti-CD25, basiliximab, daclizumab) - block IL2 receptor
- Rapamycin - mTOR inhibitor
- Corticosteroids - inhibit gene transcription and IL2 activity
What is commonest cause of microscopic haematuria in a man below 40 years?
A. IgA nephropathy
B. IgM nephropathy
C. Alport syndrome
D. Goodpasture syndrome
A. IgA nephropathy
What electolyte abnormalities occur with the use of stomach for urinary diversion?
A. Hypochloremic metabolic alkalosis
B. Hypochloremic metabolic acidosis
C. Hypochloremic metabolic alkalosis
D. Hypochloremic, hypernatremic metabolic acidosis
A. Hypochloremic metabolic alkalosis
Which statement is correct concerning the use of ureteric stents in kidney transplantation?
A. They are associated with higher risk of bleeding
B. Stents should stay for at least a month after transplantaion
C. It is not necessary when performing a uretero-ureteral anastomosis
D. There is clear evidence recommending its use in ureteral reimplantation
D. There is clear evidence recommending its use in ureteral reimplantation
The use of a double-J stent in ureteral reimplantation in transplantation:
A. Is associated with a higher risk of infections
B. Does not change the incidence of haematuria
C. Has no proven benefit
D. Is associated with at higher risk of late stenosis
A. Is associated with a higher risk of infections
Following renal transplantation, the most important factor which causes renal artery stenosis is:
A. Angulation of hte artery
B. Immunosuppressive treatment
C. Small diameter of the renal artery
D. Arterial anastomosis not perfectly carried out
D. Arterial anastomosis not perfectly carried out
Which statement about parathyroid hormone is correct?
A. It enhances tubular calcium reabsorption
B. It decreases production of 1.25 dihydroxy-vitamin D
C. It increases tubular reabsorption of inorganic phosphates
D. It enhances hydrogen ion secretion in the proximal tubule
A. It enhances tubular calcium reabsorption
Which drug may cause acute renal failure?
A. Quinolones
B. Desmopressin
C. Opiate analgesics
D. Non-steroidal anti-inflammatory drugs
D. Non-steroidal anti-inflammatory drugs
Which hormone is most important in urine production at night?
A. Aldosterone
B. Corticosteroids
C. Renin-angiotensin system
D. Vasopressin
D. Vasopressin
Oliguria is likely to be caused by pre-renal (impaired perfusion) failure rather than by intrarenal (renal parenchymal) failure, if:
A. The urine contains no cells or casts
B. The urinary sodum is less than 10mmol/l
C. The urinary osmolality is less than 350mOsm/l
D. The child has hypertension, raised central pressure and good peripheral perfusion
B. The urinary sodum is less than 10mmol/l
