Renal transplant Flashcards
(34 cards)
How long do kidney transplant grafts last?
15-18 years
What’s a deceased donor?
Brain dead or donation after circulatory death (they die after inotropes withdrawn in theatre during organ transplant)
Marginal donor - not pristine; history of HTN or blood borne virus
Live donor - best kind of graft, best survival. Normal kidneys, neg X match.
What’s Kidney donor risk index?
Takes into account characteristics of donor - how well the graft will do?
Used in the kidney allocation process
Strongest correlation to quality of kidney/survival of graft is donor age
Lifetime risk of ESKD in live donors
<1% But significantly higher than healthy non-donors
Renal transplant eligibility
Need to likely to benefit
Considerations
Comorbidities
Immunological risk - RPA, previous transplant, previous blood transfusions
Medication adherence
Primary renal disease - risk of recurrence
Balanced against risk of staying on dialysis (worse than having colon ca)
Contraindications to renal transplant
Absolute
Malignancy (skin ca is not absolute but need to be aware of due to increased risk after immunosuppression)
Uncontrolled/untreated infection e.g. bronchiectasis
Chronic infection
Unacceptable anaesthetic risk
Smoking, ETOH, psychological
Relative
Severe sun damage
Severe vascular disease
Non-adherence
What 6 things do we look at to determine immunological compatibility?
1) ABO compatibility
2) Tissue typing - HLA (A, B, DR)
- Looks at mismatch between donor and recipient
3) Panel reactivity antibody test (PRA)
- Present and peak
4) Lymphocytoxic Crossmatch (looks at the same thing as 5)
5) Flowcytometric crossmatch (looks at the same thing as 4)
6) Luminex
HLA mismatch
The less mismatch the better
This matters less now with immunosuppresion, so we still do it even if 6/6 mismatch but just need to be mindful they have a higher risk of rejection
What are the 3 types of crossmatch?
CDC crossmatch
- Mix donor cells with recipient serum
- About to get phased out
- Detects HLA and other ab, IgG, and IgM
Flow crossmatch
- Doing a similar thing but on flow cytometer
- Incubate patient serum and donor cells and see if there is interaction
- Looking at T and B cells
- More sensitive than CDC
Luminex
- Incubate patient serum with luminex beads
- Specific HLA ag on coated beads
- Detects IgG only
- Mean fluorescent intensity looks at how strong the binding is
- This is done every 3/12
We use all 3 methods at the moment to assess HLA compatibility
How to minimise blood transfusions in potential kidney transplants?
Leuco depleted blood
Avoid blood transfusions as much as possible
Can collect blood before an operation in preparation
Can give cyclosporin pre and post blood transfusion if you’re really worried to dampen down immune system
Hyperacute rejection
Rare these days
As soon as you incorporate the new kidney, it goes black on the table
Banff score?
How we score what the biopsies look like
0-3
Looks at interstitial inflammation, tubilitis, intimal arteritis, glomerulitis, peritubullar capillaries, C4d (complement), GBM double contours etc.
Acute rejection
T cell mediated or ab mediated (donor specific ab that ramp up or de novo ab that develop)
Common
Usually reversible
Chronic rejection
Hard to treat
Don’t do well
Characteristics of acute antibody-mediated rejection
Peritubular capilaritis Glomerulitis (polymorphs) Arteritis Thrombotic microangiopathy ATN Donor specific ab C4d positive stain (means complement activation)
Characteristics of chronic allograft nephropathy
Tubular atrophy Interstitial fibrosis Patchy infiltrate Arteriolar hyalinosis Glomerulopathy - Glomerulosclerosis - Reduplication of BM
Management of acute rejection
1) Biopsy essential
2) IV methylprednisolone
>90% effective
If not responding, do another biopsy
3) Lymphocyte depleting ab
4) Plasma Xchange, IVIG if there is denovo ab
5) Rescue therapy is increased immunosuppression (high dose tacrolimus, MMF)
Generally if you can turn this around, good outcomes
Number of episodes correlate with graft survival and mortality (multiple episodes of kidney damage)
mTOR inhibitors Sirolimus, everolimus MOA Benefits Concerns
Blocks signal transduction –> cell cycle arrest in G1 of T cell –> inhibits proliferation and clonal expansion of IL2 stimulated T cells
Anti-malignant properties (particularly in those with previous skin ca)
Proteinuria
Wound healing (be careful in surgery; tend not to use early after transplant)
Potentiates nephrotoxicity of CNI
When do we use IVIG?
Antibody mediated rejection (with PLEX)
?prevent rejection when clinical scenario detects reduction in other immunosuppression
CNIs
Cyclosporin and tacrolimus
MOA
Use
Key issues
Inhibit IL2 generation (interrupt signal 1 between T cell and APC)
Cornerstone of anti-rejection prophylaxis
Key issues
- CYP450 metabolism - multiple interactions
- Need to monitor levels (concentration dependent action & toxicities)
- Nephrotoxic
- Aim for high exposure early, minimise exposure late
CNI toxicity
HTN
- Caused by renal vasoconstriction and Na retention
- Develops within first few weeks of therapy
Neurotoxicity
- Mild tremor common up to 50%
- Rarely severe headache, visual abnormalities, seizures
PRES (posterior reversible encephalopathy syndrome)
- Confusion, headache, altered LOC, visual change, seizures
- Posterior white matter oedema on neuroimaging
Prophylaxis in renal transplant
CMV
- 3-6/12 CMV prophylaxis valaciclovir
PCP
- Bactrim
Polioma virus - nil
BK virus MOA Presentation Histology Diagnosis Treatment
DNA virus
Reactivation of donor derived infection (usually infected in childhood then it lies dormant in the urothelium)
Asymptomatic - just get rising creatinine
BK nephropathy - interstitial nephritis, tubular injury and necrosis
Blood (or urine) PCR
Rx: reduce immunosuppression - but be careful cause you can get BK virus and rejection at the same time
+/- antiviral (cidofovir, lefluonamide)
CVD post tranpslant
Leading cause of death
