Renal replacement therapy - transplantation

Question 1

Describe renal transplantation

Answer 1

• Transplanted kidney is placed into the iliac fossa and anastomosed to the iliac vessels
• Native kidneys usually remain in situ

Question 2

When is native nephrectomy indicated?

Answer 2

Indications for native nephrectomy include size (polycystic kidneys) and infection (chronic pyelonephritis)

Question 3

How are donor kidneys preserved?

Answer 3

o Cold storage solutions
o Minimize oedema
o Preserve integrity of tissues
o Buffer free radicals

Question 4

List some complications associated with transplant surgery

Answer 4

Vascular complications
o Bleeding
• Usually anastomotic sites
• Perirenal haematoma can be arterial or venous
o Arterial thrombosis
o Venous thrombosis
o Lymphocele - collection of lymphatic fluid within the body not bordered by epithelial lining

Urine leak from ureters

Infections

Question 5

What immunosuppressive agents are used in transplant patients?

Answer 5

Corticosteroids

Calcineurin inhibitors - Tacrolimus, Cyclosporine

Anti-proliferatives - Mycophenolate mofetil, Azathioprine

mTOR inhibitors - Sirolimus

Costimulatory signal blockers - Belatacept

Depleting agents - Basiliximab (anti-CD25), Anti-thymocyte globulin (ATG), Rituximab (anti-CD20)

Question 6

What calcineurin inhibitors are used for transplant patients?

Answer 6

Tacrolimus, Cyclosporine

Question 7

What anti-proliferative are used for transplant patients?

Answer 7

Mycophenolate mofetil, Azathioprine

Question 8

What mTOR inhibitor is used for transplant patients?

Answer 8

Sirolimus

Question 9

What costimulatory signal blockers is used for transplant patients?

Answer 9

Belatacept

Question 10

What depleting agents are used for transplant patients?

Answer 10

Basiliximab (anti-CD25)
Anti-thymocyte globulin (ATG)
Rituximab (anti-CD20)

Question 11

List some side effects of corticosteroids

Answer 11

Hypertension
Hyperglycaemia
Infections
Bone loss
GI bleeds

Question 12

List some side effects of tacrolimus

Answer 12

Hyperglycaemia
AKI
Tremor

Question 13

List some side effects of cyclosporin

Answer 13

Hirsutism
Hypertension
AKI
Gout

Question 14

List some side effects of Mycophenolate mofetil

Answer 14

Cytopenia

GI upset

Question 15

List some side effects of sirolimus

Answer 15

Lipidogenic
Diabetogenic
Pneumonia

Question 16

List some side effects of Belatacept

Answer 16

Infections

Malignancy

Question 17

List some side effects of Anti-thymocyte globulin (ATG)

Answer 17

Infections

Post-transplant lymphoproliferative disorder (PTLD)

Question 18

Describe the normal protocol for immunosuppression

Answer 18

• Induction: Basiliximab
• Maintenance: Tacrolimus + Mycophenolate + steroids
• Steroid free is possible
• Others: CNI-free using Belatacept

Question 19

What types of organ donors are there?

Answer 19

Deceased Donors
o	Donation after brain death/ DBD
-	Standard / extended criteria
o	Donation after cardiac death/DCD
-	Standard / extended criteria 

Living Donors
o	Living Related Donor
o	Living Unrelated Donors
-	Spousal
-	Altruistic
-	Paired/pooled

Question 20

What is the brain death standard criteria for organ donation?

Answer 20

Coma, unresponsive to stimuli

Apnoea off ventilator (with oxygenation) despite build up of CO2

Absence of cephalic reflexes
•	Pupillary
•	Oculocephalic
•	Oculovestibular (caloric)
•	Corneal
•	Gag
•	Purely spinal reflexes may be present

Body temperature above 34 C

Absence of drug intoxication

Question 21

What is the extended criteria for donation?

Answer 21

o Donor aged > 60y
o Donor aged 50-59 + history of hypertension, death from cerbrovascular accident or terminal creatinine of >132µmol/L

Donors with medical complexities

Question 22

Describe paired donation

Answer 22

Kidney Paired Donation (KPD) or Paired Exchange, is an approach to living donor kidney transplantation where patients with incompatible donors swap kidneys to receive a compatible kidney. KPD is used in situations where a potential donor is incompatible

Question 23

Is it safe to donate a kidney?

Answer 23

95% confidence intervals for the probability of survival among kidney donors.

Question 24

What is the risk of kidney donation?

Answer 24

• Similar patient survival to general population.
• Lower rate of ESRD compared to general population reduced.
• Compensatory increase in GFR of remaining kidney to 70% of pre-donation values
• Compensatory increase greater in younger donors.
• Older age and high BMI were associated with GFR of <60.
• Relatively short follow up time (12 years).

Question 25

List some complications of renal transplantation

Answer 25

Rejection - Cell mediated or Humoral (Ab mediated) ``` Cardiovascular o Underlying renal disease o CRF o Hypertension o Hyperlipidaemia o Post-transplant Diabetes ``` Infective o Bacterial o Viral o Fungal Malignancy o Skin o Lymphoma o Solid Cancers

Question 26

Describe T cell mediated rejection

Answer 26

Acute rejection * Lymphocytic infiltrate * Tubulitis * Endarteritis * Endothelialitis

Question 27

Describe antibody mediated rejection

Answer 27

Chronic rejection Microvascular inflammation o Neutrophil infiltration o Glomeruli o Peritubular capillaries Donor specific antibodies Positive C4d o Peritubular capillaries Biopsy shows the capillary loops of the glomerulus contain neutrophils and red cells, the lumina are obscured by swollen endothelial cells, and the peritubular capillaries contain scattered neutrophils On an immunofluorescence micrograph of a cryostat section stained with monoclonal antibody to C4d, the peritubular capillaries are brightly outlined (green), a finding typical of acute humoral rejection

Question 28

What is the most important transplant related infection?

Answer 28

Cytomegalovirus * Affects around 8% of transplant recipients, despite prophylaxis therapy. * High mortality and morbidity if untreated.

Question 29

How does CMV affect transplant patients?

Answer 29

Recipient affected via o Transmission from donor tissue o Reactivation of latent virus

Question 30

What does CMV cause in transplant patients?

Answer 30

CMV viremia ``` Tissue invasive disease: o Pneumonitis o Hepatitis o Retinitis o Gastroenteritis o Colitis o Nephritis ```

Question 31

What normally asymptomatic family of viruses can cause widespread disease in the immunocompromised?

Answer 31

Polyomaviridae ``` Family includes: • BK virus • JC virus • Murine polyoma virus • SV40 ```

Question 32

What are some risk factors for BCAN?

Answer 32

Intensity of immunosuppression o Tacrolimus, mycophenolate mofetil, antilymphocyte globulins Patient determinants o Older age, male gender, white ethnicity, DM, negative BKV serostatus (paediatric recipients) Organ determinants o Graft injury, HLA mismatches, ureteral stents Viral determinants o Changes in epitopes of viral capsid protein VP-1

Question 33

Describe the outcome and management of BCAN

Answer 33

Outcome o Allograft dysfunction o Loss of graft in 45-80% ``` Treatment o Reduce immunosuppression o Antiviral therapy o Cidofovir +/- IVIG o Leflunomide ```

Question 34

What malignancies are common following renal transplantation?

Answer 34

``` Colon Lung Breast Testicular Bladder Melanoma Leukaemia Cervical Renal ```