Transplant Flashcards by lauren floyd

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

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Drugs that interact with Tacrolimus

Fluconazole - antifungals
Diltiazem - calcium channel blockers
Clarithromycin - Marolides

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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

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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

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Complications of Sirolimus

Skin cancer
Pneumonitis
Can cause FSGS in transplant patients
Raised lipids
If used with MMF can cause anaemia

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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

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Treatment of AMR

1)PLEX and then IVIG

Ritux thereafter

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Biopsy features of AMR

Positive C4D staining
Peritubular capillaritis
Glomerulitis

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Treatment of T cell mediated rejection

Pulsed IV MTP
Switch ciclosporin to tacrolimus
Increase MMF and add in steroids
Consider ATG

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Features of T cell mediated rejection of Bx

Tubulitis
Increased inflammatory cells (mainly neutrophils and eosinophils) - causing interstitial oedema -

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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

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Biopsy findings in TMA in transplants

Double contouring
Looks like MPGN
Capillary thrombi in the glomerulus

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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

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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

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PTLD

Associated with EBV
Risk factors
- Increased IS and young age
-Recipient EBV -ve, donor +ve
-1st year from transplant

Treatment - RCHOP, Reduce IS

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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