Renal transplantation

Question 1

The principle of tissue matching?

• where does an individual HLA type come from?
• why is HLA important in rejection?

Answer 1

HLA are cell surface proteins expressed on cells.
These activate the immune system if non self and cause rejection
There are 3 important types in transplant:
HLA A
HLA B
HLA DR

-At each of A, B and DR there are 2 HLA types
1 inherited from each parent

-Donor Specific HLA Antibodies
A patient may have been exposed to a HLA Ag previously and formed Ab to this.
This leads to rejection

Question 2

briefly explain the basics of transplant rejection? (5)

Answer 2

• HL antigen binds to dendritic cells and is expresed on the outside of the Major Histocompatability Complex
• This activates T cell receptors and T cells (CD4) -when the T helper cell is activated it leads to an increasing no. of cytotoxic T cells and natural killer cells
• B cells activated by CD4 cells to produce antibody which binds to the kidney
• T helper cells also produce cytokines, interleukin 2 and complement activation causing cell lysis and transplant rejection.

Question 3

Complications of over-immunosuppression?

-management

Answer 3

BK virus
Cytomegalovirus (prophylactic valganciclovir)
Recurrent UTI
Pneumocystis jirovecii (give prophylactic co-trimoxazole)
non-melanoma skin cancer
Post transplant lymphoma

Question 4

complications of too little
immunosuppression
-histology

Answer 4

rejection
graft dysfunction and loss

-influx of inflammatory cells

Question 5

Types of rejection? (3)

Answer 5

Hyperacute- Minutes
Due to +ve Xmatch (preformed antibodies to the Tx)
Unsalvageable
Remove kidney

Acute – Usually early
T cell or B cell mediated response
Can be treated with increased immunosupression

Chronic
Immunological and vascular deterioration of the Tx
when they stop taking medication

Question 6

3 stages of immunosuppression and the drugs used at each stage?

Answer 6

induction
steriods, MMF, CyA, Tacrolimus, antibodies

Consolidation
steroids, MMF, CyA, tacrolimus

maintenance
Steroids, MMF, CyA, Tacrolimus

Question 7

Calcineurin inhibitors

• 2 examples
• mechanism of action (4)
• SE (4)
• metabolism

Answer 7

-Cyclosporin & Tacrolimus

-Act by inhibiting the activation of Th cells, therefore they:
reduce NK activation and cytotoxic T cell activation
reduce cytokine release so prevent B cell proliferation & antibody production

• renal dysfunction, hypertension, diabetes, tremors
• cytochrome p450 in the liver so lots of drug interactions

Question 8

What drugs block purine synthesis?

• mechanism of action?
• SE
• do not use with?

Answer 8

• Azathioprine and Mycophenolate
• suppression of the proliferation of lymphocytes and B cells
• Leucopaenia, anaemia, GI e.g colitis
• Azathioprine and allopurinol give aplastic anaemia

Question 9

steroids

• mode of action?
• SE

Answer 9

• act to suppress the activity of T cells and proliferation of B cells
• Osteoporosis, weight gain, infection, diabetes

Question 10

Types of kidney donor (3)

-transplant in type 1 diabetes?

Answer 10

DBD- deceased brain dead
declared brainstem dead

DCD-deceased cardiac death
those who die at cardiac arrest

live donor kidney
donated by sibling or parent

-kidney pancreas duel transplant

Question 11

suitability for transplant

-pre transplant assesment

Answer 11

-Patient should have reasonable life expectancy
not given to those waiting for dialysis

-CV risk
 (ECG, Cholesterol, ETT, Coronary Angiogram, Echocardiogram)
virology
(HBV, HCV, HIV, CMV, EBV
HBV, HCV and HIV should be treated and controlled pre transplant)
CXR
Bladder assesment
\+ co morbidity

Question 12

Contraindications for transplant (6)

Answer 12

Malignancy
Known untreated malignancy
Hx of solid tumour within 2 years (For some tumours 5 years)
Untreated TB
Severe IHD not amenable to surgery (should be carried out prior to Tx)
Severe airways disease
Active vasculitis
Severe PVD (Unusable vessels)

Question 13

transplant surgery

• procedure
• complications(6)
• post transplant care (5)

Answer 13

-extraperitoneal, stent inserted between ureter and bladder

-Bleeding (arterial or venous)
Arterial Stenosis / Thrombosis
Venous stenosis / Thrombosis
Ureteric Stricture and hydronephrosis
Wound infection

-HDU Care post op
Central Line to measure CVP
Bladder catheter for measuring urine output
IV Fluids to maintain hydration
Oxygen

Question 14

categories of transplant function- describe (3)

Answer 14

Immediate Graft Function
Urine Output good
Falling creatinine and Urea

Delayed Graft Function
Post Tx acute tubular necrosis
Tx will work after 10-30 days
Will need Haemodialysis in interim
Difficult to detect rejection ( Need Bx)

Primary non function
Transplant never works

Question 15

when the transplant fails?

Answer 15

Difficult to determine which grafts will work
U/S and Renograms to look at blood flow
Biopsy to look for rejection, ATN and cortical necrosis
Time
Dialysis to manage CRF and maintain fluid balance
Reduction in doses of medication
Patience

Question 16

long term follow up of transplant patients

Answer 16

Treatment of:
Late acute rejection
Hypertension and cardiovascular risk
Chronic allograft nephropathy
UTI
Recurrent primary renal disease
Surveillance for skin cancer