Renal replacement therapy - transplantation Flashcards
Describe renal transplantation
- Transplanted kidney is placed into the iliac fossa and anastomosed to the iliac vessels
- Native kidneys usually remain in situ
When is native nephrectomy indicated?
Indications for native nephrectomy include size (polycystic kidneys) and infection (chronic pyelonephritis)
How are donor kidneys preserved?
o Cold storage solutions
o Minimize oedema
o Preserve integrity of tissues
o Buffer free radicals
List some complications associated with transplant surgery
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
What immunosuppressive agents are used in transplant patients?
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)
What calcineurin inhibitors are used for transplant patients?
Tacrolimus, Cyclosporine
What anti-proliferative are used for transplant patients?
Mycophenolate mofetil, Azathioprine
What mTOR inhibitor is used for transplant patients?
Sirolimus
What costimulatory signal blockers is used for transplant patients?
Belatacept
What depleting agents are used for transplant patients?
Basiliximab (anti-CD25)
Anti-thymocyte globulin (ATG)
Rituximab (anti-CD20)
List some side effects of corticosteroids
Hypertension Hyperglycaemia Infections Bone loss GI bleeds
List some side effects of tacrolimus
Hyperglycaemia
AKI
Tremor
List some side effects of cyclosporin
Hirsutism
Hypertension
AKI
Gout
List some side effects of Mycophenolate mofetil
Cytopenia
GI upset
List some side effects of sirolimus
Lipidogenic
Diabetogenic
Pneumonia
List some side effects of Belatacept
Infections
Malignancy
List some side effects of Anti-thymocyte globulin (ATG)
Infections
Post-transplant lymphoproliferative disorder (PTLD)
Describe the normal protocol for immunosuppression
- Induction: Basiliximab
- Maintenance: Tacrolimus + Mycophenolate + steroids
- Steroid free is possible
- Others: CNI-free using Belatacept
What types of organ donors are there?
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
What is the brain death standard criteria for organ donation?
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
What is the extended criteria for donation?
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
Describe paired donation
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
Is it safe to donate a kidney?
95% confidence intervals for the probability of survival among kidney donors.
What is the risk of kidney donation?
- 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).
List some complications of renal transplantation
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
Describe T cell mediated rejection
Acute rejection
- Lymphocytic infiltrate
- Tubulitis
- Endarteritis
- Endothelialitis
Describe antibody mediated rejection
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
What is the most important transplant related infection?
Cytomegalovirus
- Affects around 8% of transplant recipients, despite prophylaxis therapy.
- High mortality and morbidity if untreated.
How does CMV affect transplant patients?
Recipient affected via
o Transmission from donor tissue
o Reactivation of latent virus
What does CMV cause in transplant patients?
CMV viremia
Tissue invasive disease: o Pneumonitis o Hepatitis o Retinitis o Gastroenteritis o Colitis o Nephritis
What normally asymptomatic family of viruses can cause widespread disease in the immunocompromised?
Polyomaviridae
Family includes: • BK virus • JC virus • Murine polyoma virus • SV40
What are some risk factors for BCAN?
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
Describe the outcome and management of BCAN
Outcome
o Allograft dysfunction
o Loss of graft in 45-80%
Treatment o Reduce immunosuppression o Antiviral therapy o Cidofovir +/- IVIG o Leflunomide
What malignancies are common following renal transplantation?
Colon Lung Breast Testicular Bladder Melanoma Leukaemia Cervical Renal
