Renal Transplant Basics

Question 1

Why is it important to know the RKF/time of dialysis vintage?

Answer 1

• Helps to give an idea of prognosis, urgency of transplant
• Definition of pre-emptive transplant: not yet initiated on dialysis, or dialysis initiation < 2 weeks
• Current wait list 8-10 years since vintage dialysis (Singapore)

Question 1

Why is it important to be cognisant of the underlying etiology of ESKD?

Answer 1

(A) Identifying risk for recurrence
- Highest risk of recurrence post-transplant: IgAN, primary FSGS, lupus nephritis, DM neph

(B) Identify risk of complications post-transplant / IST considerations post-transplant
- E.g. patients with ESKD 2’ autoimmune etiology may require higher IST doses
- Patients with ADPKD may also need to be screened for complications related to PKD e.g. aneurysms
- Patients with DM nephropathy may have worsening DM control after initiation of steroids

Question 2

What are the important compatibility matching?

Answer 2

• Blood group (ABO compatibility)
• HLA
• Anti-HLA antibodies and DSA
• Donor characteristics
• Recipient characteristics

Question 3

What are Sensitisation Events?

Answer 3

• Blood transfusion
• Pregnancy (esp spousal donor - directed against paternal HLA antigens)
• Previous transplant
• Unknown - postulated cross reactivity with microbial agents

Question 4

What are the available De-sensitisation Agent or treatment?

Answer 4

• Rituximab - CD20, binds to B cells -> may cause flow B cell to turn positive
• Immunoabsorption (IA) > 4 PV
• PEX > 1.5 PV

Question 5

What are the available Induction agents?

Answer 5

• Thymoglobulin (ATG) - polyclonal Ab to B/T cells, NK cells, plasma cells, rapid induced apoptosis of CD3+ T cells
• Simulect (basiliximab) - monoclonal Ab to IL-2 of T cells

Question 6

What are the available Maintenance immunosuppressants?

Answer 6

• Corticosteroids (prednisolone)
• MMF or MPA vs azathioprine
• CNI - cyclosporin or tacrolimus
• mTOR - everolimus or sirolimus (associated with poor wound healing)

Question 7

What is Brenner hypothesis and secondary FSGS and why is it important in the context of transplant donor?

Answer 7

• Chronic glomerular hypertension causes mechanical stretch of podocytes leading to injury and activation of RAAS and over-expression of AT1 receptors causing glumerulosclerosis
• Seen in rat models with 1 and 2/3 kidneys removed, remaining 1/3 kidney showed FSGS changes

Question 8

DDKT Investigation Workup

Answer 8

1. Bloods: FBC, RPext, LFT, coag panel, GXM
2. CXR
3. ECG
4. COVID RNA PCR
5. Infective screening:
   - Hep B (HBsAg, Anti-HBs, anti-HBc total)
   - Hep C (anti-HCV)
   - Hep E (Hep E PCR)
   - HIV (HIV Ag/Ab)
   - EBV (anti-EBV VCA IgG)
   - CMV (CMV IgG antibody)
   - Dengue serology (Dengue duo)
   - NAAT for HIV/Hep B/Hep C
   - Syphilis screen
   - VZV (VZV IgG)
6. G6PD quantitative
7. HbA1c
8. Beta-HCG for pre-menopausal women

If XM and FPRA negative:
1. HLA class I & II Ab identification (Luminex)
2. HLA DP , DQA , DQB (ordered all 3 separately)
3. HLA flow XM with pronase

If XM positive or FPRA positive or repeat transplant case:
1. HLA class I & II Ab identification (Luminex)
2. HLA DP , DQA , DQB (ordered all 3 separately)
3. HLA flow XM with pronase
4. HLA CAD full XM

Question 9

Infective risk for CMV and its treatment

Answer 9

• Highest risk in D+/R-, lowest risk in D-/R-
• NUH practises hybrid treatment: high risk treat with pre-emptive valgancyclovir, moderate risk on prophylaxis
• Prominent side effect of valgancyclovir: pancytopenia
• Alternative valacyclovir - high dose, also less effective