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23 Cards in this Set

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What combination of immunosuppresants is usually used in renal transplantation?
• Corticosteroids
• Mycophenolate mofetil (or mycophenolic acid or azathioprine)
• Tacrolimus or cyclosporin
What is the standard maintenance immunosuppression for renal transplantation?

What are some of the support therapies used to combat some of the AEs from immunosuppression?

What combination is used pre-op?
• Basiliximab (as induction Tx)
• Tacrolimus
• Mycophenolate mofetil
• Prednisolone

Pre-op:
• Mycophenolate mofetil
• Basiliximab
• Tacrolimus
• Timentin
• Methylprednisolone
Support Tx:
• Omeprazole
• Nystatin
• Bactrim DS
• Valganciclovir
• Statins
What is basiliximab used for?

What are some alternative options?
IL-2 receptor antagonist used as induction therapy:
• Reduce risk of acute rejection
• Allows for gradual or delayed intro of tacrolimus (or CyA)
• Improves survival
• Offers improvements to QOL

Alternatives:
• Daclizumab (no longer marketed in Aus)
• Thymoglobuline (option if reaction to basiliximab or very high risk of infection)
What areas does low dose tacrolimus have advantage over low & standard dose CyA and low dose sirolimus?
• Renal function
• Acute rejection
• Allograft survival
Diltiazem can be used as a sparing agent with which drugs?
• Cyclosporin
• Tacrolimus
What is the treatment for cellular rejection?
• Pulse corticosteroids
- Methylprednisolone
- Withhold prednisolone whilst on methylpred then restart at higher dose & rapidly wean back to maintenance

• T-cell depleting antibodies
- e.g. thymoglobuline

• IV immunoglobulin

• Alter maintenance immunosuppresion
What is the treatment for antibody mediated rejection?
Treatment options include alone or in combination:
• Pulse steroids
• Anti-T cell antibodies
• IV immunoglobulin
• Alter maintenance immunosuppression
• Plasma exchange
• Rituximab (depletes B cells not T)
• Splenectomy (if refractory)
What is chronic allograft nephropathy and what are possible risk factors?
Most common cause of graft failure after the 1st yr.

Renal allograft dysfunction in the absence of active acute rejection, drug toxicity or other diseases.
• Deteriorating graft function (slowly rising SrCr)
• Increasing proteinuria
• Worsening hypertension

Risk factors:
• Acute rejection
• HLA mismatch
• Prior sensitisation
• Noncompliance with immunosuppressive Tx
• Hypertension, hyperlipidaemia
• Delayed graft function
• Immunosuppressive Tx
• Proteinuria
• Smoking
What are some management strategies for chronic allograft nephropathy?
• Prevent acute rejection during first 12 months
• Minimise calcineurin inhibitor exposure in later years
• Switching calcineurin inhibitors to sirolimus
• Control of hypertension & hyperlipidaemia
What is PCP prophylaxis and what are the agents used?
Pneumocystis Carinii Pneumonia prophylaxis (usually for 6 months post-transplant)

First line:
• Trimethoprim + sulfamethoxazole (various dosage regimens, 3 times weekly to prevent thrombocytopenia, neutropenia)

Alternatives:
• Pentamidine nebulised monthly
• Dapsone daily
Why is CMV prophylaxis needed and how does CMV present as?

What prophylactic agents are used?
CMV is the major cause of morbidity & mortality in solid organ transplantation in the first 6 months post transplant.

Presents as:
• Pneumonitis
• Hepatitis
• Encephalitis
• GI disease

Prophylactic agents:
• Valaciclovir
• Ganciclovir
• Valganciclovir (lowest pill burden)
What are some of the supportive therapies used and what are their roles?
Omeprazole
• Prevent peptic ulcer disease
• Ease reflux symptoms

Diltiazem
• Tacrolimus or cyclosporin sparing agent
• May counterbalance renal constriction induced by calcineurin inhibitors

Statins
• Reduce hyperlipidaemia & cardiovascular disease in renal transplant pts
• Pleitropic effects may modify rejection risk
• Associated with improvements in graft function
• Early introduction appears important
What are some complications of renal transplantation?
• Infection
• Malignancy
• Hypertension
• Hyperlipidaemia
• Post transplant diabetes mellitus
• Bone disease
• Obesity
• Renal impairment
• Gout
Discuss malignancy as a complication of renal transplantation..
• Use of immunosuppressives increases long term risk of malignancies

• Risk of malignancies two to fourfold more common in heart compared to renal transplants
Discuss infection as a complication of renal transplantation...
• Most common infections immediately post transplant include UTIs, wound, respiratory & IV line infections, oropharyngeal candidiasis.

• Opportunistic infections most likely in first 3-6 months post transplant (e.g. CMV, PCP, HSV, VZV)

• 6 months post treatment - similar risk to general population
Discuss hypertension as a complication of renal transplantation...
• Calcineurin inhibitors induce renal vasoconstriction & increase sodium reabsorption.

• Corticosteroids increase sodium retention.

• Important to treat as HT is a risk factor for allograft failure & increased mortality
Discuss hyperlipidaemia as a complication of renal transplantation..
• Calcineurin inhibitors & mTOR inhibitors both increase lipids

• Cyclosporin > tacrolimus
• Sirolimus shown to have a substantial increase in total cholesterol, LDL and TGs

• Corticosteroids have a dyslipidaemic effect

• Additionally obesity, hyperglycaemia, insulin resistance, proteinuria & treatment with beta blockers or diuretics may contribute

• Treat with HMG-CoA reductase inhibitors (care with rhabdomyolysis esp with cyclosporin due to CYP450 interaction)
Discuss post transplant diabetes mellitus as a complication of renal transplantation...
Both calcineurin inhibitors & corticosteroids contribute (tacrolimus > cyclosporin)

Risk factors:
• Increasing age
• African Americans & Hispanics
• Family Hx of diabetes
• Hep C
• Hypertension
• Obesity

Serious complication as associated with increased CV risk and increased graft loss.
Discuss bone disease as a complication of renal transplantation...
• Decreased bone formation & mineralisation with persistent resorption

• Pre-existing renal osteodystrophy a contributing factor

• Transplant recipients experience a rapid decline in BMD in first 6-12 months post transplant

• Corticosteroids increase osteoclastic resorption, decrease osteoblastic activity, decrease intestinal Ca absorption & increase renal Ca loss

• CyA also assoc. with decrease in BMD
Discuss gout as a complication of renal transplantation..
Due to calcineurin inhibitors, diuretics, pre-existing gout & renal impairment.

Treatment problematic:
• Avoid NSAIDs - nephrotoxicity
• Increased risk of myopathy, GI disturbances & renal toxicity w/ concomitant administration of CyA & colchicine
• MUST reduce AZA dose if using allopurinol
• Often treat with prednisolone
What happens with ABO incompatible transplants?
Now possible to overcome blood group incompatibility.
• Plasma exchange
• IVIG
• Immunoadsorption (blood group impregnated columns, remove specific antibody)
• Splenectomy
• Rituximab
What are some HLA desensitisation protocols?
• IVIG
• Plasma exchange
• Rituximab
What is the role of the clinical pharmacist in transplantation?
• Patient education
- Good medication education is essential to ensure pt understands importance & rationale for taking medications
- Education & compliance aids (medication lists, dosette boxes)

• Ensure appropriate drug therapy
• TDM
• Management of drug interactions
• Advise on conversion & administration of IV immunosuppressants
• Advise on administration of thymoglobuline, basiliximab, etc
• Provide drug information to nurses & medical staff