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23 Cards in this Set
- Front
- Back
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What combination of immunosuppresants is usually used in renal transplantation?
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• Corticosteroids
• Mycophenolate mofetil (or mycophenolic acid or azathioprine) • Tacrolimus or cyclosporin |
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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 |
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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) |
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What areas does low dose tacrolimus have advantage over low & standard dose CyA and low dose sirolimus?
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• Renal function
• Acute rejection • Allograft survival |
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Diltiazem can be used as a sparing agent with which drugs?
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• Cyclosporin
• Tacrolimus |
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What is the treatment for cellular rejection?
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• 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 |
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What is the treatment for antibody mediated rejection?
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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) |
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What is chronic allograft nephropathy and what are possible risk factors?
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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 |
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What are some management strategies for chronic allograft nephropathy?
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• Prevent acute rejection during first 12 months
• Minimise calcineurin inhibitor exposure in later years • Switching calcineurin inhibitors to sirolimus • Control of hypertension & hyperlipidaemia |
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What is PCP prophylaxis and what are the agents used?
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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 |
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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) |
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What are some of the supportive therapies used and what are their roles?
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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 |
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What are some complications of renal transplantation?
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• Infection
• Malignancy • Hypertension • Hyperlipidaemia • Post transplant diabetes mellitus • Bone disease • Obesity • Renal impairment • Gout |
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Discuss malignancy as a complication of renal transplantation..
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• Use of immunosuppressives increases long term risk of malignancies
• Risk of malignancies two to fourfold more common in heart compared to renal transplants |
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Discuss infection as a complication of renal transplantation...
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• 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 |
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Discuss hypertension as a complication of renal transplantation...
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• 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 |
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Discuss hyperlipidaemia as a complication of renal transplantation..
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• 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) |
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Discuss post transplant diabetes mellitus as a complication of renal transplantation...
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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. |
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Discuss bone disease as a complication of renal transplantation...
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• 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 |
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Discuss gout as a complication of renal transplantation..
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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 |
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What happens with ABO incompatible transplants?
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Now possible to overcome blood group incompatibility.
• Plasma exchange • IVIG • Immunoadsorption (blood group impregnated columns, remove specific antibody) • Splenectomy • Rituximab |
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What are some HLA desensitisation protocols?
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• IVIG
• Plasma exchange • Rituximab |
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What is the role of the clinical pharmacist in transplantation?
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• 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 |
