Kidney Transplant Medicine Flashcards
(23 cards)
Side effects for transplant donor
Decreased creatinine clearance
Higher BP
Higher proteinuria
Increased risk of renal failure
Nil change in survival
Why Kidney-Pancreas Transplant?
Fro type 1 diabetic esp. with hypoglycaemia unawareness
Increased short term risk of acute rejection and infection
Good survival and improved QOL
Immunology of transplant
APO compatibility
HLA compatibility important –> immunogenic response
Panel reactive antibody - PRA
PRA = 100 = hyper-responsive immune system
Hyperacute rejection
Rare, early untreatable
Due to pre-formed antibodies to the kidney
Black kidney on the table
Predictable by cytotoxic crossmatch
Acute rejection
15-25% of transplants
Donor specific antibody formation Diagnosed by biopsy: - Cellular = pred responsive - Vascular = not pred responsive - needs T cell suppression - Antibody mediated
Chronic rejection
Common - 30% of trnasplants
Unknown aetiology - immune and non-immune aspects
Progressive renal dysfunction
Chronic allograft nephropathy
Tubular atrophy, intersititial fibrosis, and infiltrates
Due to:
- Time with graft
- CNI toxicity
- HTN
- DM
- GN
- Nephrotoxins
- Ischaemia
Intervention to stop rejection
Use multiple agents to block all three signals between APC and T cell as well as steroids
–> stops proliferation and activation of immune system
Use higher doses to stop acute rejection in the immediate post transplant period
Use prophylaxis to prevent opportunistic infections
Induction Agents
Basiliximab
- CTLA-4Ig
- Targets activated T cells only –> blocks effects
Thymoglobulin
- Kills all T cells
- Can cause flu-like illness, meningitis, cytopenias, cancer and infections
Signal 1 inhibition
Cyclosporine and Tacrolimus
Inhibit IL-2 generation
Problems:
- CYP450 metabolism effects
- Concentration dependant action and toxicity = monitor levels
- Nephrotoxic, HTN and increased lipids
- Increase risk of cancer
- Tac = risk of DM
Pregnancy safe
Anti-proliferative agents
MMF and Azathiopurine
Blocks IMPDH –> inhibits purine synthesis
Problems:
- GI SEs
- Myco = lower levels with CNIs
- Bone marrow suppression
mTOR Inhibitors - Signal 3 inhibitors
Everolimus and rapamycin
Binds to FKBP-12 –> binds to mTOR
Results in inhibition of IL-2 co-stimulatory signalling –> inhibition of DNA and RNA synthesis
Problems:
- Higher proteinuria
- Higher risk of rejection compared to CNIs
- Kaposi’s Sarcoma
- Stomatitis and acneform rash
- Increases lipids
Early Complications of kidney transplant
Infections:
- CMV - 6 weeks
- BK virus - .5-2yrs
- PCP
- UTI
Acute rejection
Drug side effects:
- ARF
- Tremor
- Mood
- GIT
- Bone
Cancer - Post transplant lymphoproliferative disorder
Surgical complications
Late complications of kidney transplant
Infections:
- HPV
- VZV - 50% mortality if primary infection
- HSV
- Fungal infections
Chronic rejection
Chronic allograft nephropathy
Drug effects:
- Hair and skin
- Kidney
- Bone
- Cardiovascular
Cancer:
- Carcinoma - skin, bowel and lung
- Lymphoma
Cardiovascular disease
Recurrence of primary renal disease
BK Polyomavirus
DNA virus
Infected in childhood –> persistence in kidney
Reactivated by immunosuppression
Usually 6 months + post transplant
Diagnosis -
- Worsening renal function +/- haematuria
- Biopsy of transplant
- SV40 antigen positive
- Blood or urine PCR
Treatment = reduce immunosuppression
Prophylaxis
CMV = valacyclovir/valgancyclovir
PCP = co-trimoxazole
Osteoporosis = vitamin D and Calcium and bisphosphonate
Cause of Death with function graft
Cardiovascular Disease +++
Cancer:
- Skin
- Viral related cancers
- Lung and bowel cancers
Disease recurrence after transplant
GN - IgA, FSGS, MCGN II and membraneous
1 in 10 transplanted with diseases will recur
Post transplant new onset Diabetes
Combination of insulin resistance and Insulin deficiency
Insulin resistance:
- Steroids
- CNIs
- mTOR inhibitors
- Inflammation
Insulin deficiency:
- Tacrolimus
- mTOR
- age
–> INCREASED RISK OF CARDIOVASCULAR DISEASE +++
Pregnancy and dialysis
Need daily haemodialysis
Poor outcomes
Pregnancy and transplant
Fertility improves after transplant
Must wait 1 yr after transplant
Use CCSs, AZA, tacrolimus
Role of belatecept in immunosuppression?
CTLA-4 blocker
More episodes of acute rejection
Better GFR and survival with standard donors at 7yrs
Better GFR with extended donors at 7yrs
Higher rates of post transplant lymphoproliferative disorder
Advantages of extended hours home haemodialysis?
Calcium and phosphate control better
Better fluid control
Less vascular stiffness and calcification
Requires more interventions to keep fistula patent
