2. HistoryHistory
๏ฎ 19091909 - The first kidney transplant experiments were performed in- The first kidney transplant experiments were performed in
humans in France using animal kidneys (rabbit).humans in France using animal kidneys (rabbit).
๏ฎ 19331933 - The first human-to-human kidney transplant was performed.- The first human-to-human kidney transplant was performed.
๏ฎ 19541954 - The first successful human-to-human transplant from one twin- The first successful human-to-human transplant from one twin
to another by Dr. Joseph E. Murray and his colleagues at Peter Bentto another by Dr. Joseph E. Murray and his colleagues at Peter Bent
Brigham Hospital in Boston.Brigham Hospital in Boston.
๏ฎ 19621962 โ The first cadaveric donor kidney transplant at Peter Bentโ The first cadaveric donor kidney transplant at Peter Bent
Brigham Hospital (now Brigham & Women's Hospital) in Boston.Brigham Hospital (now Brigham & Women's Hospital) in Boston.
3.
4.
5. General Principle of ImmunosuppressionGeneral Principle of Immunosuppression
๏ฎ Primary immune responses are more easily repressed than secondaryPrimary immune responses are more easily repressed than secondary
(memory)(memory)
๏ฎ Suppression is more likely to be achieved if therapy is begun beforeSuppression is more likely to be achieved if therapy is begun before
exposure to the immunogenexposure to the immunogen
๏ฎ Different immunosuppressants have different effects on differentDifferent immunosuppressants have different effects on different
immune reactions and mediatorsimmune reactions and mediators
6. IntroductionIntroduction
๏ฎ Advances in transplant immunosuppression have contributed toAdvances in transplant immunosuppression have contributed to
thethe
๏ฎ decrease in the frequency of acute rejectiondecrease in the frequency of acute rejection
๏ฎ increase in graft survivalincrease in graft survival
๏ฎ longevity for renal allograft recipientslongevity for renal allograft recipients
๏ฎ Proliferation of agents meansProliferation of agents means
๏ฎ more optionsmore options
๏ฎ different mechanisms of actiondifferent mechanisms of action
๏ฎ more complicated management schemesmore complicated management schemes
๏ฎ increase potential for drug-drug interactions and complex side effectincrease potential for drug-drug interactions and complex side effect
profilesprofiles
7. Categories of AgentsCategories of Agents
๏ฎ Induction agentsInduction agents
๏ฎ Monoclonal or polyclonal antibodiesMonoclonal or polyclonal antibodies
๏ฎ Administered intravenously immediately following surgeryAdministered intravenously immediately following surgery
๏ฎ Maintenance agentsMaintenance agents
๏ฎ PrednisonePrednisone
๏ฎ CNIs form the cornerstone of immunosuppressive therapyCNIs form the cornerstone of immunosuppressive therapy
๏ฎ Antiproliferative agents: Cellcept, Imuran, RapamuneAntiproliferative agents: Cellcept, Imuran, Rapamune
๏ฎ Triple agents / withdrawal / avoidance / conversionTriple agents / withdrawal / avoidance / conversion
8.
9. Immunologic HistoryImmunologic History
๏ฎ SensitizationSensitization
๏ฎ First or re-transplantFirst or re-transplant
๏ฎ RejectionRejection
๏ฎ InfectionInfection
๏ฎ HLA-matchingHLA-matching
13. Anti-IL-2 Receptor AntibodiesAnti-IL-2 Receptor Antibodies
๏ฎ Basiliximab (Simulect)Basiliximab (Simulect)
๏ฎ Chimeric antibody (75% human, 25% mouse)Chimeric antibody (75% human, 25% mouse)
๏ฎ Dosing: 20 mg i.v. pre-op and POD# 4Dosing: 20 mg i.v. pre-op and POD# 4
๏ฎ Daclizumab (Zenapax)Daclizumab (Zenapax)
๏ฎ Humanized (95% human, 5% mouse)Humanized (95% human, 5% mouse)
๏ฎ Dosing: 1 mg/kg pre-op and q 2 w for total 6 dosesDosing: 1 mg/kg pre-op and q 2 w for total 6 doses
๏ฎ Not effective for treating rejectionNot effective for treating rejection
14.
15. Calcineurin InhibitorsCalcineurin Inhibitors
๏ฎ CyclosporineCyclosporine
๏ฎ Different preparation are not equivalentDifferent preparation are not equivalent
๏ฎ Sandimmune (cyclosporine, USP)Sandimmune (cyclosporine, USP)
๏ฎ Gengraf (cyclosporine, USP โ Modified)Gengraf (cyclosporine, USP โ Modified)
๏ฎ Neoral (cyclosporine, USP โ Microemulsion)Neoral (cyclosporine, USP โ Microemulsion)
๏ฎ Tacrolimus (FK 506, Prograf)Tacrolimus (FK 506, Prograf)
16.
17. Advantages of CsA MicroemulsionAdvantages of CsA Microemulsion
formulationformulation
๏ฎ Twice the bioavailabilityTwice the bioavailability
๏ฎ Less intraindividual and interindividual variabilityLess intraindividual and interindividual variability
๏ฎ Reduced time (more than 30 percent) to maximal concentration (Tmax)Reduced time (more than 30 percent) to maximal concentration (Tmax)
๏ฎ Absorption and drug levels are less susceptible to the effects of foodAbsorption and drug levels are less susceptible to the effects of food
(particularly fatty foods),(particularly fatty foods),
๏ฎ Not dependent upon bile salts for absorption.Not dependent upon bile salts for absorption.
21. Cyclosporin: MonitoringCyclosporin: Monitoring
๏ฎ Cyclosporin: C2 LevelCyclosporin: C2 Level
๏ฎ < 6 months: 1000-1500 ng/ml< 6 months: 1000-1500 ng/ml
๏ฎ > 6 months: 800-900 ng/ml> 6 months: 800-900 ng/ml
๏ฎ Little evidence from prospective studies to support the theoreticalLittle evidence from prospective studies to support the theoretical
benefits of C2 monitoring. Potential dose reductions in stable patientsbenefits of C2 monitoring. Potential dose reductions in stable patients
may reduce costs, but no short-term clinical benefit is seen.*may reduce costs, but no short-term clinical benefit is seen.*
*Knight, S R. et al. Transplantation 2007 Jun; 83(12):1525-1535
22. Tacrolimus (Prograf): MonitoringTacrolimus (Prograf): Monitoring
Low riskLow risk Mod RiskMod Risk High riskHigh risk
0-6 m0-6 m 6-126-12 ng/mlng/ml 8-128-12 ng/mlng/ml 8-158-15 ng/mlng/ml
6-12 m6-12 m 5-85-8 ng/mlng/ml 5-105-10 ng/mlng/ml 6-126-12 ng/mlng/ml
> 12 m> 12 m 4-84-8 ng/mlng/ml 5-105-10 ng/mlng/ml 6-126-12 ng/mlng/ml
S Hariharan. Am J Kidney Dis. 2006. 47(S2):S22-S36.
23. CNI Side EffectsCNI Side Effects
EventEvent CommentsComments
HepatotoxicityHepatotoxicity ๏ฎ Liver function should be monitored atLiver function should be monitored at
regular intervalsregular intervals
CardiovascularCardiovascular
๏ฎ HypertensionHypertension
๏ฎ HypercholesterolemiaHypercholesterolemia
๏ฎ Fewer tacrolimus-treated patients requireFewer tacrolimus-treated patients require
antihypertensive medicationsantihypertensive medications
๏ฎ Tacrolimusโ impact on lipid levels is less thanTacrolimusโ impact on lipid levels is less than
that seen with cyclosporinethat seen with cyclosporine
Glucose intoleranceGlucose intolerance ๏ฎ Recent studies indicate little differencesRecent studies indicate little differences
between tacrolimus and cyclosporinebetween tacrolimus and cyclosporine
NeurotoxicityNeurotoxicity
๏ฎ TremorTremor
๏ฎ HeadacheHeadache
๏ฎ InsomniaInsomnia
๏ฎ ParesthesiaParesthesia
๏ฎ Seen more often with tacrolimus andSeen more often with tacrolimus and
generally improve with dose reductiongenerally improve with dose reduction
24. CNI Side EffectsCNI Side Effects
EventEvent CommentsComments
Cosmetic side effectsCosmetic side effects
๏ฎ Gingival hypertrophyGingival hypertrophy
๏ฎ HirsutismHirsutism
๏ฎ AlopeciaAlopecia
๏ฎ Use of steroids may exaggerateUse of steroids may exaggerate
developmentdevelopment
๏ฎ Gingival hypertrophy and hirsutism areGingival hypertrophy and hirsutism are
associated with cyclosporineassociated with cyclosporine
๏ฎ Calcium channel blockers can exacerbateCalcium channel blockers can exacerbate
gingival hypertrophygingival hypertrophy
๏ฎ Alopecia can occur with tacrolimusAlopecia can occur with tacrolimus
MalignancyMalignancy
๏ฎ Skin cancersSkin cancers
๏ฎ Cervical cancerCervical cancer
๏ฎ LymphoproliferativeLymphoproliferative
disordersdisorders
๏ฎ Incidence appears to be a function ofIncidence appears to be a function of
overall amount and duration ofoverall amount and duration of
immunosuppression rather than any specificimmunosuppression rather than any specific
agentagent
25. CNI Side EffectsCNI Side Effects
๏ฎ Nephrotoxicity (Striped fibrosis)Nephrotoxicity (Striped fibrosis)
๏ฎ TMATMA
๏ฎ Type IV RTAType IV RTA
26. CNICNI
More with TacrolimusMore with Tacrolimus More with CyclosprinMore with Cyclosprin
Neurologic SENeurologic SE HypertensionHypertension
GI side effectsGI side effects HyperlipidemiaHyperlipidemia
PTDMPTDM
AlopeciaAlopecia HirsutismHirsutism
Hypertrophic cardimyopathyHypertrophic cardimyopathy
in childrenin children
Gingival hyperplasiaGingival hyperplasia
29. Nonmetabolic Interactions With CNIsNonmetabolic Interactions With CNIs
Drug TypeDrug Type CommentsComments
๏ฎ Nephrotoxic agentsNephrotoxic agents
๏ฎ NSAIDsNSAIDs
๏ฎ VancomycinVancomycin
๏ฎ GanciclovirGanciclovir
๏ฎ AminoglycosidesAminoglycosides
๏ฎ Monitor renal functionMonitor renal function
๏ฎ NSAIDs may have increasedNSAIDs may have increased
nephrotoxicity with hepatic impairmentnephrotoxicity with hepatic impairment
๏ฎ Potassium-sparing diureticsPotassium-sparing diuretics ๏ฎ Hyperkalemia has been reportedHyperkalemia has been reported
๏ฎ AntacidsAntacids ๏ฎ Magnesium and aluminum antacids mayMagnesium and aluminum antacids may
inhibit absorption of CNIsinhibit absorption of CNIs
๏ฎ If necessary, should be taken 2 hours afterIf necessary, should be taken 2 hours after
CNI doseCNI dose
๏ฎ HMG-CoA reductaseHMG-CoA reductase
inhibitors (statins)inhibitors (statins)
๏ฎ Increased risk of rhabdomyolysis, boneIncreased risk of rhabdomyolysis, bone
marrow suppressionmarrow suppression
30. CNICNI
๏ฎ Tacrolimus v. SandimmuneTacrolimus v. Sandimmune
๏ฎ acute rejection may be less with tacrolimus.acute rejection may be less with tacrolimus.
๏ฎ similar graft survivalsimilar graft survival
๏ฎ Tacrolimus v. NeoralTacrolimus v. Neoral
๏ฎ In some studies, tacrolimus has reportedly had lower acute rejectionIn some studies, tacrolimus has reportedly had lower acute rejection
rates.rates.
๏ฎ Despite this, both agents are associated with similarly excellentDespite this, both agents are associated with similarly excellent
allograft survival rates, although some studies report an advantage ofallograft survival rates, although some studies report an advantage of
one agent over the other.one agent over the other.
31. CNICNI
๏ฎ In a meta-analysis and meta-regression study of 123 reports from 30In a meta-analysis and meta-regression study of 123 reports from 30
trials (4102 patients), the followings were found.trials (4102 patients), the followings were found.
๏ฎ At six months, graft loss was significantly reduced in tacrolimusAt six months, graft loss was significantly reduced in tacrolimus
treated recipients and this effect persisted up to three years.treated recipients and this effect persisted up to three years.
๏ฎ At one year, tacrolimus treated patients had less acute rejection.At one year, tacrolimus treated patients had less acute rejection.
๏ฎ Treating 100 recipients with tacrolimus instead of cyclosporin for theTreating 100 recipients with tacrolimus instead of cyclosporin for the
first year after transplantation avoids 12 patients having acutefirst year after transplantation avoids 12 patients having acute
rejection and two losing their graft but causes an extra five patients torejection and two losing their graft but causes an extra five patients to
develop insulin dependent diabetes.develop insulin dependent diabetes.
Webster AC. Et al. BMJ 2005 Oct 8;331(7520):810
32. Dosing of Adjuvant AgentsDosing of Adjuvant Agents
AgentAgent Daily DoseDaily Dose MonitoringMonitoring
AzathioprineAzathioprine 1-3 mg/kg qd1-3 mg/kg qd None availableNone available
MMF (Cellcept)MMF (Cellcept) 750 mg-1.5 g bid750 mg-1.5 g bid MPA:1.6 โ 2.75 mg/L*MPA:1.6 โ 2.75 mg/L*
SirolimusSirolimus 2-5 mg qd2-5 mg qd 5-15 ng/mL (whole5-15 ng/mL (whole
blood trough level)blood trough level)
CorticosteroidsCorticosteroids 5-10 mg qd5-10 mg qd None availableNone available
*Borrows R, et al. Am J Transplant 2006(6):12-128
33.
34. Antiproliferative AgentsAntiproliferative Agents
AgentAgent Daily DoseDaily Dose MonitoringMonitoring
Azathioprine (Imuran)Azathioprine (Imuran) 1-3 mg/kg qd1-3 mg/kg qd None availableNone available
Mycophenolate mofetilMycophenolate mofetil
(MMF, Cellcept(MMF, Cellcept))
750 mg-1.5 g bid750 mg-1.5 g bid
Not requiredNot required
MPA:1.6 โ 2.75 mg/L*MPA:1.6 โ 2.75 mg/L*
*Borrows R, et al. Am J Transplant 2006(6):12-128
35. Side Effects of Antiproliferative AgentsSide Effects of Antiproliferative Agents
Drug and Side EffectsDrug and Side Effects Clinical ImplicationsClinical Implications
๏ฎ AzathioprineAzathioprine
๏ฎ LeukopeniaLeukopenia
๏ฎ AnemiaAnemia
๏ฎ ThrombocytopeniaThrombocytopenia
๏ฎ HepatitisHepatitis
๏ฎ CholestasisCholestasis
๏ฎ PancreatitisPancreatitis
๏ฎ Complete blood counts should beComplete blood counts should be
performed regularly to monitor forperformed regularly to monitor for
hematologic side effectshematologic side effects
๏ฎ MMFMMF
๏ฎ LeukopeniaLeukopenia
๏ฎ AnemiaAnemia
๏ฎ ThrombocytopeniaThrombocytopenia
๏ฎ DiarrheaDiarrhea
๏ฎ NauseaNausea
๏ฎ Bloating dyspepsiaBloating dyspepsia
๏ฎ VomitingVomiting
๏ฎ EsophagitisEsophagitis
๏ฎ GastritisGastritis
๏ฎ Complete blood counts should beComplete blood counts should be
performed regularly to monitor forperformed regularly to monitor for
hematologic side effectshematologic side effects
๏ฎ GI side effects are more commonGI side effects are more common
when dose exceeds 1 g bid andwhen dose exceeds 1 g bid and
respond to dose reduction or morerespond to dose reduction or more
frequent administration of smallerfrequent administration of smaller
dosesdoses
36. Drug Interactions WithDrug Interactions With
Antiproliferative AgentsAntiproliferative Agents
DrugDrug InteractionsInteractions
AzathioprineAzathioprine ๏ฎ Coadministration with ganciclovir, ACE inhibitors,Coadministration with ganciclovir, ACE inhibitors,
carbamazepine, clozapine, or cotrimoxazole cancarbamazepine, clozapine, or cotrimoxazole can
lead to the exacerbation of hematologic toxicitylead to the exacerbation of hematologic toxicity
๏ฎ Allopurinol is contraindicated, as concomitantAllopurinol is contraindicated, as concomitant
administration can lead to life-threateningadministration can lead to life-threatening
myelosuppressionmyelosuppression
MMFMMF ๏ฎ Coadministration with ganciclovir, ACE inhibitors,Coadministration with ganciclovir, ACE inhibitors,
carbamazepine, clozapine, or co-trimoxazole cancarbamazepine, clozapine, or co-trimoxazole can
lead to the exacerbation of hematologic toxicitylead to the exacerbation of hematologic toxicity
๏ฎ Administration with tacrolimus may potentiate GIAdministration with tacrolimus may potentiate GI
side effectsside effects
37. MyforticMyfortic
๏ฎ Enteric-coated MMFEnteric-coated MMF
๏ฎ Intended to reduce GI side effects but has not been proved in clinical trialsIntended to reduce GI side effects but has not been proved in clinical trials
๏ฎ Dose equivalentDose equivalent
๏ฎ 180 mg Myfortic = 500 mg MMF180 mg Myfortic = 500 mg MMF
38. Mycophenolate v. AzathioprineMycophenolate v. Azathioprine
๏ฎ Several studies, particularly some initial pivotal reports, found that acuteSeveral studies, particularly some initial pivotal reports, found that acute
rejection rates were lower with mycophenolate. However, these studies mayrejection rates were lower with mycophenolate. However, these studies may
be flawed.be flawed.
๏ฎ Given current evidence, azathioprine and mycophenolate mofetil appear toGiven current evidence, azathioprine and mycophenolate mofetil appear to
be similar in terms of acute rejection rates and long-term allograft survivalbe similar in terms of acute rejection rates and long-term allograft survival
rates.rates.
39. Mycophenolate v. AzathioprineMycophenolate v. Azathioprine
๏ฎ MYSS TrialMYSS Trial
๏ฎ 336 patients undergoing a deceased donor renal transplant336 patients undergoing a deceased donor renal transplant
๏ฎ randomly assigned to mycophenolate mofetil or azathioprinerandomly assigned to mycophenolate mofetil or azathioprine
๏ฎ both groups also receiving cyclosporine microemulsion andboth groups also receiving cyclosporine microemulsion and
corticosteroids. Corticosteroids were continued for the first six monthscorticosteroids. Corticosteroids were continued for the first six months
(phase A), after which they were slowly withdrawn and patients were(phase A), after which they were slowly withdrawn and patients were
followed for another 15 or more months (phase B).followed for another 15 or more months (phase B).
Remuzzi G. et al. Lancet 2004 Aug 7;364(9433):503-12.
40. Mycophenolate v. AzathioprineMycophenolate v. Azathioprine
๏ฎ MYSS TrialMYSS Trial
๏ฎ The incidence of clinical rejection was the same for bothThe incidence of clinical rejection was the same for both
mycophenolate and azathioprine in phase A (34 and 35 percent,mycophenolate and azathioprine in phase A (34 and 35 percent,
respectively) and phase B (16 and 12 percent, respectively).respectively) and phase B (16 and 12 percent, respectively).
๏ฎ Rates of allograft loss, and serum creatinine concentration were theRates of allograft loss, and serum creatinine concentration were the
same in both groups.same in both groups.
๏ฎ However, mycophenolate was approximately 15 times moreHowever, mycophenolate was approximately 15 times more
expensive than azathioprineexpensive than azathioprine
Remuzzi G. et al. Lancet 2004 Aug 7;364(9433):503-12.
42. Mycophenolate v. AzathioprineMycophenolate v. Azathioprine
๏ฎ the long-term risk/benefit profile of MMF and azathioprine therapy inthe long-term risk/benefit profile of MMF and azathioprine therapy in
combination with cyclosporine Neoral is similar.combination with cyclosporine Neoral is similar.
๏ฎ In view of the cost, standard immunosuppression regimens for kidneyIn view of the cost, standard immunosuppression regimens for kidney
transplantation should perhaps include azathioprine rather than MMF.transplantation should perhaps include azathioprine rather than MMF.
45. Side Effects of SirolimusSide Effects of Sirolimus
Drug and Side EffectsDrug and Side Effects Clinical ImplicationsClinical Implications
๏ฎ SirolimusSirolimus
๏ฎ HypercholesterolemiaHypercholesterolemia
๏ฎ HypertriglyceridemiaHypertriglyceridemia
๏ฎ HypertensionHypertension
๏ฎ RashRash
๏ฎ LeukopeniaLeukopenia
๏ฎ AnemiaAnemia
๏ฎ ThrombocytopeniaThrombocytopenia
๏ฎ Interstitial pneumonitisInterstitial pneumonitis
๏ฎ Delayed wound healingDelayed wound healing
๏ฎ Mouth ulcersMouth ulcers
๏ฎ ProteinuriaProteinuria
๏ฎ EdemaEdema
๏ฎ Pneumonitis occasionally resolvedPneumonitis occasionally resolved
in discontinuation of sirolimusin discontinuation of sirolimus
46. Drug Interactions With SirolimusDrug Interactions With Sirolimus
๏ฎ As sirolimus is metabolized by the same pathway as the CNIs (P-450As sirolimus is metabolized by the same pathway as the CNIs (P-450
3A4), interactions are the same3A4), interactions are the same
๏ฎ Sirolimus has been shown to raise blood levels of cyclosporine and MMFSirolimus has been shown to raise blood levels of cyclosporine and MMF
๏ฎ Sirolimus should be administered 4 hours after cyclosporine orSirolimus should be administered 4 hours after cyclosporine or
tacrolimustacrolimus
๏ฎ Sirolimus blood levels are raised by cyclosporineSirolimus blood levels are raised by cyclosporine
๏ฎ Proper monitoring is advisedProper monitoring is advised
50. Side Effects of CorticosteroidsSide Effects of Corticosteroids
Drug and Side EffectsDrug and Side Effects Clinical ImplicationsClinical Implications
๏ฎ CorticosteroidsCorticosteroids
๏ฎ AcneAcne
๏ฎ Cushingoid facial appearanceCushingoid facial appearance
๏ฎ HirsutismHirsutism
๏ฎ Mood disordersMood disorders
๏ฎ HypertensionHypertension
๏ฎ Glucose intoleranceGlucose intolerance
๏ฎ CataractsCataracts
๏ฎ OsteoporosisOsteoporosis
๏ฎ Growth retardation in childrenGrowth retardation in children
๏ฎ May potentiate adverseMay potentiate adverse
events of CNIsevents of CNIs
51. Tailoring Drug RegimensTailoring Drug Regimens
๏ฎ Refractory rejectionRefractory rejection
๏ฎ Changing from cyclosporine to tacrolimus has proven successful inChanging from cyclosporine to tacrolimus has proven successful in
reversing rejectionreversing rejection
๏ฎ Cardiovascular diseaseCardiovascular disease
๏ฎ High blood pressure and high cholesterol may be lowered with changesHigh blood pressure and high cholesterol may be lowered with changes
from cyclosporine to tacrolimusfrom cyclosporine to tacrolimus
๏ฎ High cholesterol may also be lowered by replacing sirolimus with MMFHigh cholesterol may also be lowered by replacing sirolimus with MMF
๏ฎ DiabetesDiabetes
๏ฎ De novoDe novo presentation of diabetes may improve with lowering of steroidpresentation of diabetes may improve with lowering of steroid
dosedose
๏ฎ Rarely, patients switched from tacrolimus to cyclosporine may seeRarely, patients switched from tacrolimus to cyclosporine may see
improvements of glucose metabolismimprovements of glucose metabolism
52. ๏ฎ HirsutismHirsutism
๏ฎ Changing from cyclosporine to tacrolimus generally reverses hirsutismChanging from cyclosporine to tacrolimus generally reverses hirsutism
๏ฎ Gingival hyperplasiaGingival hyperplasia
๏ฎ Replacing cyclosporine with tacrolimus can alleviate gingival hyperplasiaReplacing cyclosporine with tacrolimus can alleviate gingival hyperplasia
๏ฎ Withdrawing calcium channel blockers may also lead to improvements inWithdrawing calcium channel blockers may also lead to improvements in
gingival tissuegingival tissue
๏ฎ TremorTremor
๏ฎ If dose reduction of the CNI does not stop tremor, consider switching toIf dose reduction of the CNI does not stop tremor, consider switching to
the alternate therapythe alternate therapy
๏ฎ GoutGout
๏ฎ Convert azathioprine to MMF if allopurinol must be usedConvert azathioprine to MMF if allopurinol must be used
Tailoring Drug RegimensTailoring Drug Regimens
53. Deficiencies with ImmunosuppressiveDeficiencies with Immunosuppressive
TherapyTherapy
๏ฎ Patientโs compliance and adherencePatientโs compliance and adherence
๏ฎ Side effects of long-term exposureSide effects of long-term exposure
๏ฎ Long-term comorbidities induced by these agentsLong-term comorbidities induced by these agents
๏ฎ Need to continue these agents for lifeNeed to continue these agents for life
๏ฎ Inability to induce toleranceInability to induce tolerance
54. ConclusionConclusion
๏ฎ Proper immunosuppression is critical to the survival of the renal allograftProper immunosuppression is critical to the survival of the renal allograft
๏ฎ Understanding proper dosing and monitoring becomes especially criticalUnderstanding proper dosing and monitoring becomes especially critical
when comorbid conditions are involvedwhen comorbid conditions are involved
๏ฎ Some side effects are inherent with a suppressed immune system; othersSome side effects are inherent with a suppressed immune system; others
occur as the result of specific agentsoccur as the result of specific agents
๏ฎ Experimental drug protocols that eliminate or withdraw steroids and CNIsExperimental drug protocols that eliminate or withdraw steroids and CNIs
remain untested in the long term and must be eyed with cautionremain untested in the long term and must be eyed with caution
๏ฎ Patient education regarding compliance should be ongoing throughout thePatient education regarding compliance should be ongoing throughout the
life of the transplantlife of the transplant
