Transplant Flashcards
How does BK present post transplant
Initially high viral load in the urine before going into the blood stream and causing graft issues
DECOY CELLS in the urine is diagnostic
Present with erythematous skin changes
Mainly asymptomatic increase in creat
Treatment - reduce IS.
Cidofovir can be used as antiviral
Drugs that interact with Tacrolimus
Fluconazole - antifungals
Diltiazem - calcium channel blockers
Clarithromycin - Marolides
Contraindications to transplantation
Malignancy, infection life expectancy <5yr
- Need to be cancer free for 2 yrs
- Breast / bowel/ lymphoma = cancer free for >5yrs
Cancers insitu such as bladder, prostate, skin, renal can be transplanted straight away if surgery was curative
Induction immunosuppressive agents
Non Depleting
- Basiliximab = Anti CD25, used most commonly, given day 0 and day 4
Depleting
- ATG = T cell depletion, used in acute rejection and indication, can cause reactions
- Campath (aka Alemtuzumab) = Anti CD 52, Can cause persistent lymphopenia, used mainly in SPK
- OKT3 = used as treatment for refractory rejection
Complications of Sirolimus
Skin cancer
Pneumonitis
Can cause FSGS in transplant patients
Raised lipids
If used with MMF can cause anaemia
What is meant by Antibody mediated rejection versus Cellular rejection
Antibody mediated Rejection (AMR)
-T and B cells involved
- Development of anti-donor antibodies = positive DSAs
-Trends to occur after a sensitizing event
- Causes activation of the classical pathway = Increased C4d
Cellular Rejection
- T cell driven process with macrophage activation
- Most common type of rejection especially in the first 3 months
Treatment of AMR
1)PLEX and then IVIG
Ritux thereafter
Biopsy features of AMR
Positive C4D staining
Peritubular capillaritis
Glomerulitis
Treatment of T cell mediated rejection
Pulsed IV MTP
Switch ciclosporin to tacrolimus
Increase MMF and add in steroids
Consider ATG
Features of T cell mediated rejection of Bx
Tubulitis
Increased inflammatory cells (mainly neutrophils and eosinophils) - causing interstitial oedema -
TMA in transplants
TMA occurs in 2 contexts
1) Recurrent HUS
2) New TMA = Caused by = Acute AMR, infection, CNI
treatment - Stop CNI, Eculizumab +/- PLEX
Biopsy findings in TMA in transplants
Double contouring
Looks like MPGN
Capillary thrombi in the glomerulus
Transplant Glomerulopathy
Is a chronic histopathological diagnosis
Often due to chronic ABMR
DSAs tend to be positive
Chronic renal impairment and UPCR
Bx = double contouring
CNI Toxicity - Bx findings
Tends to be with prolonged use of tacrolimus, levels >8
Biopsy
- Stripe fibrosis and tubule vaculosation
Treatment = Switch to Sirolimus, or if raised UPCR then just reduce dose of tac
PTLD
Associated with EBV
Risk factors
- Increased IS and young age
-Recipient EBV -ve, donor +ve
-1st year from transplant
Treatment - RCHOP, Reduce IS
Cancer risks In transplant patients
Skin cancer - squamous
Renal cell ca - especially if previously on dialysis
PTLD - EBV
Kaposis sarcoma = HHV8 infection
RAS in transplant
tends to occur 3-6 months post transplant
Present with increased BP and reduced eGFR
May also get unilateral leg claudication and bruit over transplant
CMV treatment
Prophylactic - If donor +ve but recipient -ve
Valganciclovir (po) for 90 days
Treatment of infection
- BD valganciclovir
-IV ganciclovir for those that cant tolerate oral
Note - if develops neutro/lymphopenia on ganciclovir then add in GCSF but don’t stop
Recurrent disease - most to least common
FSGS - High chance graft loss
IgA - Low chance of graft loss
Membranous
MCGN
Diabetes - Low chance graft loss
HUS - high chance graft loss
Risk factors for acute AMR
Delayed graft function
Sensitizing event
Repeated transplantation
Higher HLA mismatch
Immune checkpoint inhibitors and transplantation
Immune checkpoint inhibitors upregulate the immune system so can cause acute rejections. In addition= can cause AKI by other mechanisms such as AIN, TMA, IgA nephropathy, C3 Glomerulopathy and pauci-immune GN.
To minimize the risk of rejection switch from tacrolimus to sirolimus, and increase the doses of corticosteroids before initiating ICIs.
Cancer screening post transplant
mammography every 2 years beyond the age of 50.
Cervical screening is as per general population, with 5-yearly cervical screening in individuals over the age of 50.
Skin cancer surveillance = twice-annual check by a trained healthcare professional up to 5 years post-transplant, with an annual review from 5 years.
Post transplant diabetes
Common and needs to be treated often with insulin due to the potential effects on graft function
Hepatitis C is strongly associated with risk of developing post transplant diabetes
Criteria for live donor
If BP indeterminate in clinic then needs ambulatory / 24 monitoring
BP needs to be controlled < 140/90 on one or two antihypertensive agents.
Urinary ACR < 30
BMI up to 30 is acceptable
Features of ureteral stenosis
Tends to occur post stent removal around 6 months
If donor is of older age this is a risk factor
Tend to present with gradual, asymptomatic worsening of renal function
Investigation with anterograde pyelogram
What are complement dependent crossmatch (CDC) and Flow crossmatch (Fcxm)
Checks for donor and recipient cross matching of B + T cells = which are essentially DSAs. If positive then very likely to reject and contraindication to transplant.
Flow crossmatch - Fcxm - similar to the above but more sensitive. If negative CDC but positive FCXM then will likely need desensitization but its not a contraindication to transplant
Graft Intolerance Syndrome
Inflammation caused by failed renal allografts left in situ, usually presented with fever, poorly controlled hypertension, abdominal pain, gross haematuria, and enlargement of the graft.
It is always associated with elevated acute phase reactants (ESR, CRP), hypoalbuminaemia, and resistant anaemia.
Recurrence of FSGS in transplant
Common initially after transplant
Risk factors:
-Those that developed ESRD in teenage years
-Disease course rapid
-Previous recurrence in transplant
Treatment = 1)PLEX, 2) Standard triple IS and ACE-inhibitor
Long courses of PLEX may be needed if UPCR remains high
Unsafe vaccinations in transplant and IS patients
Live vaccines:
-Shingles
-Oral typhoid
-Yellow fever
-BCG
-MMR
-oral Polio
BANNFF criteria for TCMR - acute and chronic
Active TCMR
IA=Moderate tubulitis and Inflammation
IB = Severe tubulitis and inflammation
IIA = Mild arteritis
IIB = Severe arteritis
III = Severe and fibrinoid necrosis
Chronic Active TCMR
1A - As above but scarred cortical inflammation
IB - as above but scarred cortical inflammation
II-fibrosis with nononuclear cell inflammation
Calcium phosphate crystals / phosphate nephropathy in transplant biopsy
Positive Von Kossa stain is diagnostic
Negative birefringence under polarised light
Often caused by phosphate supplements post biopsy
CNI induced pain syndrome
Raised ALP, Joint effusion, marrow oedema and joint pain
Caused by increased cyclosporine levels which can lead to intraosseous vasoconstriction causing pain.
Treatment is usually by nifedipine, reducing CNI levels or switching ciclosporin to tacrolimus
Minimum eGFR a donor can have to donate
> 60ml/min
Parathyroidectomy in transplant
Aim to do it before transplantation where possible.
There are worse outcomes in those with parathyroidectomy post transplant
If not able to do before (e.g DCD transplant) then aim for 1 year post transplant when graft function is stable and IS is reduced
Indications = PTH >500 if on cinacalcet and >1000 if not on cinacalcet or gland diameter >10mm
Transplant Renal Vein thrombosis
First few weeks from transplant
Presents with hematuria, oligoanuria, painful and swollen graft
risk factors:
- right donor kidney (as it has a shorter renal vein)
-prolonged ischemic time
-vascular injuries of the donor organ
-older age of the donor.
- pediatric recipient
-peri-operative hypotension.
- kink in the allograft vein or injury to the vascular endothelium
imaging = angiography
Treatment =surgical thrombectomy.
Graft loss remains very common
Features of Parvovirus B19
Causes Pure red cell aplasia - reduced Hb and reticulocyte count
What RBC transfusion requirements are needed for transplant patients
Irradiated blood products
Post transplant infections
1-6 months
- Viral - CMV, HSV, VAZ
-EBV BK
-TB
-opportunistic
> 6 months
-typical community infections
-BK, EBV, PTLD
Treatment of CMV pneumonitis
IV gancilovir
IV IG
Treatment of end organ CMV disease should be continued for min of 3 weeks
