Kidney Transplant Medicine Flashcards
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
