Clinical Care of Renal Transplant Recipients: An Internist’s Guide
Matthew R. Weir, M.D.Professor and DirectorDivision of Nephrology
University of Maryland School of Medicine
Overview• Short-term risks• Long-term risks
– Erosion of graft function– Cardiovascular disease– malignancy
• Drug – Drug interactions• Future opportunities
Overview• Short-term risks• Long-term risks
– Erosion of graft function– Cardiovascular disease– malignancy
• Drug – Drug interactions• Future opportunities
What are the short-term risks?
• Rejection• Donor factors leading to poorer outcome• Recipient death
– Operative complications– Infection– Malignancy– Cardiovascular disease
• Complications of immunosuppressive therapy
Short-Term Risks: Infection• First 6 weeks: standard post-surgical issues
including UTI, line infection, thrombophlebitis, pneumonia/atelectasis, wound infection, thrush
• After 6 weeks: opportunistic infection including CMV, EBV, PCP, listeria, aspergillus, etc.
• Chemoprophylaxis: clotrimazole, TMS, valganciclovir
Overview• Short-term risks• Long-term risks
– Erosion of graft function– Cardiovascular disease– malignancy
• Drug – Drug interactions• Future opportunities
Acute rejection rates at one year have improved considerably since the
mid-1990s1,2
1. OPTN/SRTR 2006 Annual Report.2. OPTN/SRTR 2007 Annual Report.
60
50
40
30
20
10
0
Inci
denc
e (%
)
1996 1997 1998 1999 2000 2001 2002 2003 2004
Year
2005
Longer-term outcomes remain a challenge in kidney
transplantation
ANZDATA 31st annual report 2008 (http://www.anzdata.org.au/anzdata/AnzdataReport/31stReport/Ch08Txpart2.pdf)
Primary graft survival of deceased donors by year of transplant to 31/12/07: Australia and NZ
Possible reasons why short-term improvements have not changed the long-term attrition rate
•Increased immunosuppression to prevent early acute rejection generates subsequent graft loss from over-immunosuppression
•Long-term attrition rate is a separate process driven by calcineurin inhibitors or other chronic injury
•Late immunosuppression minimization and/or non-compliance may play a role
Meier-Kriesche H-U WTC 2006.
Why hasn't improved early graft survival resulted in better late graft survival?
• Immunosuppression may have early benefits but late adverse effects on graft survival
• Late graft failure may occur via mechanisms unrelated to immune injury
• Immunosuppression may be inadequate late because of nonadherence and minimization regimens
BK nephropathy, other late infections, malignancies, CVD
CNI nephrotoxicity, recurrent disease, senescence
Multiple and/or late acute rejection episodes, subclinical rejection, AMR
ALTERNATIVE MECHANISMS FOR
EARLY KIDNEY GRAFT FAILURE
Ccr
Time
Ccr at return to dialysisCcr at return to dialysis
Good FunctionGood Function
Accelerated Accelerated SlopeSlopeReduced Reduced
InterceptIntercept
Disease and medical trends: Keys to
long-term success
•Graft survival–Acute rejection renal function1
–One year survival long-term survival2
•Patient survival–Cardiovascular disease3
–Post-transplant malignancy41. Meier-Kreische HU, et al. Am J Transplant. 2004;4:378–383.2. Hariharan S, et al. Kidney Intl. 2002;62:311–318.3. Meier-Kreische HU, et al. Transplantation. 2003;75:1291–1295.4. Campistol J, et al. JASN. 2006; 17: 581–589.
What are the important late risks?
• Donor factors leading to poorer outcome
• Recipient death– Cardiovascular disease
– Malignancy
– Infection
• Late graft loss– Chronic allograft nephropathy
– Subclinical ACR or AMR
– Infection
Death with a functioning graft is the most common cause of graft loss in kidney transplant recipients beyond the first year after transplantation
1. Peeters J, et al. Kidney Int. 1995;48(Suppl 52):S97S101. 2. Kasiske B L. et al. Coronary Artery Disease. Presented at the American Society of Nephrology Renal Week 2006 San Diego November, 14-19, 2006.
Death56%
Chronic rejection
21%
Noncompliance
13%
Other6%
Recurrence4% Cause of death2
USRDS 1st kidney transplants 1995–2003(excluding 30% unknown)
Cause of graft loss*1
*beyond the first year after transplantation
Cardiovascular disease43.5%
Infection26.3%
Malignancy10.7%
Other19.4%
•Cardiovascular disease is much more common among renal transplant recipients compared to the general population
•The greater incidence of CVD is not entirely explained by traditional risk factors, (blood pressure, cholesterol, glucose). Thus, other factors may be involved (immunosuppression, rejection, infection?)
Kasiske BL et al. J Am Soc Nephrol 2000;11:1735-1743
Cardiovascular risk and kidney transplantation
1.00
0.90
0.80
0.70
0.60
0.50
0.40Older Younger Older Younger Older Younger Older Younger
--Diabetic-- -Non-Diabetic- Diabetic -Non-diabetic-
----------Smoker---------- ----------Non-Smoker----------
10-
year
su
rviv
al w
itho
ut IH
D
Observed and expected risk for ischemic heart disease after
renal transplantation
Meier-Kriesche, Kaplan et al. Transplantation 2003.
0 12 24 36 48 60 72 84 96 108 12090
92
94
96
98
100
2.6-4.0
2.2-2.5
1.9-2.11.7-1.8
1.5-1.61.3-1.4<1.3
Scr mg/dl@1 /RR
Months post-transplant
% C
ardi
ovas
cula
r de
ath
free
sur
viva
l
1.01.031.19
1.371.49
1.67
2.26
Cardiovascular Death Events in 48,832 KTX by SCr at One Year Post-
Transplant
Relationship Between CKD and CVD1
CKD = chronic kidney disease; CVD = cardiovascular disease; CV = cardiovascular.1. Menon V et al. Am J Kidney Dis. 2005;45:223–232.
CVD
CKD
TraditionalCV risk factors
Non-traditionalCV risk factors
CKD is a risk factor for CVD, and CVD may be a risk factor for the progression of CKD
Graded and Independent Relationship Between Estimated Glomerular Filtration Rate (GFR) and CVD Outcomes*
*Adjusted for baseline age, sex, income, education, coronary disease, chronic heart failure, stroke or transient ischemic attack, peripheral artery disease, diabetes, hypertension, dyslipidemia, cancer, hypoalbuminemia, dementia, liver disease, proteinuria, prior hospitalizations, and subsequent dialysis requirement.
Shastri S et al. Am J Kidney Dis. 2010 Jul 2. [Epub ahead of print].
The key understanding is The key understanding is that patients with CKD that patients with CKD
benefit as much as non-CKD benefit as much as non-CKD patients with appropriate patients with appropriate
medications and therapies, if medications and therapies, if not more, because of their not more, because of their
increased risk!increased risk!
Decreased GFR has consistently Decreased GFR has consistently been found to be an independent been found to be an independent risk factor for CVD outcomes and risk factor for CVD outcomes and
all cause mortality!all cause mortality!
Cardiovascular Mortality Is Higher in Patients With ESRD
Adapted from Foley RN et al. Am J Kidney Dis. 1998;32(5 Suppl 3):S112–S119.
GP Male
GP Female
GP Black
GP White
Dialysis Male
Dialysis Female
Dialysis Black
Dialysis White
Transplant
Age (years)
An
nu
al m
ort
alit
y (%
)
25-34 35-44 45-54 55-64 65-74 75-84 ≥85
0.001
0.01
0.1
1
10
100
Traditional and Nontraditional Risk Factors Increase CVD Event Risk in Patients With CKD1
CVD = cardiovascular disease; CKD = chronic kidney disease; LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol; Apo = apolipoprotein.1. Shastri S et al. Am J Kidney Dis. 2010;56:399-417.
Traditional Risk Factors
Older age
Male sex
Hypertension
High LDL-C
Low HDL-C
Diabetes
Smoking
Physical inactivity
Menopause
Family history of heart disease
Left ventricular hypertrophy
White race
Non-Traditional Risk Factors
Anemia
Volume overload
Abnormal mineral metabolism
Electrolyte imbalances
Albuminuria
Lipoprotein(a) and Apo(A) isoforms and lipoprotein remnants
Homocysteine
Oxidative stress/inflammation
Malnutrition
Thrombogenic factors
Sleep disturbances
High sympathetic tone
Altered nitric oxide/endothelin balance
Particular to individuals with CKD
The Transplant Kidney
• Optimal GFR 50-60 ml/min, less in situations of ischemia/reperfusion injury, marginal donors, nephrotoxic drugs or rejection
• Risk for hyperfiltration injury
• Pre-existing milieu of hypertension, diabetes and vascular disease
• Hypertension
• Diabetes
• Dyslipidemia
• Renal Disease
Cardiovascular Risk Profile of the Renal Transplant
Recipient
Appreciate that we have no prospective randomized
controlled trials to evaluate optimal treatment regimens and
goals in patients with kidney transplants!
Pathogenesis of Hypertensionin Renal Transplant Recipients
Mailloux LU et al. Am J Kidney Dis. 1998;32(suppl 3):S120–S141. Kew CE II et al. J Renal Nutrition. 2000;10:3–6.
• Pre-existing essential hypertension• General-population risk factors
(obesity, smoking, alcohol, excessive salt intake) • Renal dysfunction/rejection• Renal-transplant artery stenosis• Effects of native kidneys• Hypertensive donor• Immunosuppressive drugs
Association of Hypertension at 1 YearWith Decreased Graft Survival
SBP = systolic blood pressureOpelz G et al. Kidney Int. 1998;53:217–222.
% g
raft
s su
rviv
ing
50
60
70
80
90
100
0
0 1 2 3 4 5 6 7
Years post-transplantation
SBP No. pts
< 120 2,805120–129 4,488130–139 5,961140–149 6,670
150–159 4,443
160–169 2,925170–179 1,217
³ 180 1,242
Does treatment of high blood pressure in renal transplant recipients reduce graft loss and patient death?
Probably!
• No outcome studies have been performed
• It is likely that these high risk patients will derive benefit for the heart, brain and transplant kidney
Drug Therapy: Treatment
Diuretics: As needed to control volume: more studies need to focus on the advantages of thiazides vs loop diuretics
Beta-blockers: Heart rate control, CAD
Alpha blockers: BPH, outflow obstruction
ACEI and ARB
• Preferred treatment strategies
antihypertensive
antiproteinuric
antiproliferative
ACEI/ARB in Renal Transplantation
• Retrospective open cohort study• N=2031, University of Vienna• 1990-2003, ACE use increased 9%-47%, ARB
0%-18% at the end of the observation period• Medication and co-morbidities were analyzed as
time-dependent variables in cox regression analyses.
• Ten year patient survival:74% ACE/ARB vs 55% in no ACE/ARB, p<.001
• Ten year graft survival: 59% in ACE/ARB group vs 41% in no ACE/ARB, p=.002
Heinze G, et al. JASN 2006;17:889-899
Kaplan-Meier estimates of patient survival. Angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor
blockers (ACEI/ARB) users lived significantly longer compared with noACEI/ARB patients (log rank: P < 0.001).
Kaplan-Meier estimates of actual graft survival counting death as event. ACEI/ARB therapy was
associated with longer graft survival (log-rank: P = 0.002).
Systematic Review of RAS Blockade in Kidney Transplantation
• 21 randomized trials• n=1549• Median follow-up: 27 months• eGFR decreased by 5.8 ml/min• Hct decreased by 3.5 %• Proteinuria decreased by 470 mg/day• No change in serum potassium• Not enough power to see an effect on patient or
graft survival
Hiremath S, et. al AmJ Transplant 2007; 7:2350-2360
Calcium Channel Blockers
• Robust antihypertensive properties, despite salt consumption
• Afferent glomerular dilators
? Good effect with calcineurin inhibitors
? Deleterious effect with glomerular capillary pressure
• Best combined with ACEI or ARB
Diabetes in Kidney Transplant Patients
• Associated with reduced patient survival
• Associated with reduced graft survival Histologic appearance of diabetic kidney disease within 5 years.
1. UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865. 2. Holman RR, et al. N Engl J Med. 2008;359:1577-1589. 3. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329;977-986. 4. Nathan DM, et al. N Engl J Med. 2005;353:2643-2653. 5. Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559. 6. Patel A, et al. N Engl J Med. 2008;358:2560-2572. 7. Duckworth W, et al. N Engl J Med. 2009;360:129-139. 8. Ismail-Beigi F, et al. Lancet. 2010;376:419-430.
Study Microvascular CVD Mortality
UKPDS1,2
DCCT/EDIC3,4
ACCORD5,8
ADVANCE6
VADT7
Impact of Intensive Glycemic Therapy
Summary of Major Clinical Trials
Long-term follow-up Initial trial
Cumulative Incidence of the First Occurrence of Nonfatal MI, Stroke, or Death From CVD, T1D
Cum
ulat
ive
Inci
denc
e
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years from Study Entry
Risk reduction 42% 95% CI: 9% to 63%
P = 0.02
0.120.12
0.100.10
0.080.08
0.060.06
0.040.04
0.020.02
0.000.00
Conventional
Intensive
Nathan DM et al. N Engl J Med. 2005:353:2643-2653.
Longer studies?
2010 15
Earlier intervention?
Cumulative Incidence of an Impaired Glomerular Filtration Rate, According to Treatment Group.
The DCCT/EDIC Research Group. N Engl J Med 2011;365:2366-2376.
Rationale for Lipid Lowering Clinical Trials in the CKD Population
• CKD and ESRD patients are at increased risk of cardiovascular complications
• CKD and ESRD patients have abnormal lipid profiles
• Secondary analyses of lipid lowering studies indicated statin treatment improved CV outcomes in CKD patients
• Secondary analyses of these studies also demonstrated slowing of CKD progression
• Need for randomized placebo-controlled statin trials in CKD and ESRD patients
1. Scandinavian Simvastatin Survival Study (4S). Lancet.1994;344(8934):1383–1389.2. Shepherd J et al. N Engl J Med. 1995;333(20):1301–1307.3. Heart Protection Study Collaborative Group. Lancet. 2002;360(9326):7–22. 4. Seliger SL et al. Kidney Int. 2002;61(1):297–304.5. Liao JK. Am J Cardiol. 2005;96(5A):24F–33F.6. Fellström BC et al. Kidney Int. 2003;63(Suppl 84):S204–S206.
Mechanism of CVD Development in
Patients With Uremia
Immuno-deficiency(T- & B- cell,phagocytosis,Ig-formation
Accelerated Atherosclerosis
Uremia
Dyslipidemia
(TG↑, ApoB↑,
ApoA1 ↓, HDL↓)Atherogenic
lipid fractions (ox_LDL,
small dense LDL)
Oxidative stress(ROS, AGE, AOPP)
MalnutritionInflammatoryactivity
ADMA↑
Endothelialdysfunction
T
B
Ab
TG, triglycerides; HDL, high density lipoprotein; LDL, low density lipoprotein; ROS, reactive oxygen species; AGEs, advanced glycation end products; AOPP, advanced oxidation of plasma proteins; ADMA, asymmetric dimethylarginine
Fellström BC et al. Kidney Int. 2003;63(Suppl 84):S204–S206.
ALERT• n = 2102 renal transplant recipients
• Randomized controlled trial (60 months)
• Primary endpoint: cardiac death, non-fatal MI, or cardiac procedures
• Fluvastatin (40-80 mg) vs placebo
• 17% RRR (p = 0.139), but fewer cardiac deaths and MI in treatment group (p = 0.005)
Holdaas et al. Lancet 2003;361:2024-2031.
SHARP: Eligibility
• History of chronic kidney disease– not on dialysis: elevated creatinine on 2 occasions
• Men: ≥1.7 mg/dL (150 µmol/L)• Women: ≥1.5 mg/dL (130 µmol/L)
– on dialysis: haemodialysis or peritoneal dialysis• Age ≥40 years• No history of myocardial infarction or coronary
revascularisation• Uncertainty: LDL-lowering treatment not
definitely indicated or contraindicated
Randomised(9438)
Randomised(886)
Not re-randomised(168)
Placebo(4191)
Simvastatin(1054)
Simva/Eze(4193)
Simv/Eze(4650)
Placebo(4620)
SHARP: Randomisation structure
Median follow-up 4.9 yearsLost to mortality follow-up 1.5%
0 1 2 3 4 5 Years of follow-up
0
5
10
15
20
25
Prop
ortio
n su
fferin
g ev
ent (
%)
Risk ratio 0.83 (0.74-0.94) Logrank 2P=0.0021 Placebo
Simv/Eze
SHARP: Atherosclerotic Events(Lancet 2011;377:2181)
SummaryNevertheless, given the data from the HPS and the SHARP study, we feel that there is a strong argument to abandon a threshold-based algorithm for treating hyperlipidemia. Rather it may be advisable to treat those with high risk for atherosclerotic cardiac events regardless of initial LDL level, and to treat with a potent dose of a statin alone or in combination with a second line drug to achieve a marked (at least 40%) reduction in LDL, at least to ATP-III LDL goal levels.
CKD Resets the Focus on CV Risk Reduction Strategies
• BP <130/80 mmHg?
• Evaluate and treat lipids
• Extinguish microalbuminuria/proteinuria?
• Reduction in dietary salt/saturated fat
• Intensify glycemic control
• Control anemia
• Control calcium / phosphorus balance
• Anti-platelet therapy
The increased risk of malignancy in kidney transplant patients
Kasiske BL, et al. Am J Transplant. 2004;4:905–913.
Colon, lung, prostate, gastric, esophagus, pancreas, ovary and breast
Testes and urinary, bladder
Cutaneous melanoma, leukemia, liver and gynecological tumors
Kidney
Kaposi sarcoma, PTLD, skin cancer
Moderate Risk
High risk
Cancer rates vs. general population
2
3
5
15
>20
Based on 2419 renal transplant recipients from the Munich Großhadern transplantation center
2520151050
60
50
40
30
20
10
0
Cum
ulat
ive
tum
or in
cide
nce
(%)
10.6 %8.4 %
19.7 %17.9 %
38.8 %31.2 %
49.3 %39.7 %
28.8 %26.9 %
2.2 %5.2 %
14.9 %
21.7 %
9.5 %
All tumorsSolid tumors (without skin cancer)Age-adjusted normal population
Time after transplantation (years)
Cumulative tumor incidence after renal transplantation
Wimmer CD, et al. Kidney Int. 2007;71:1271–1278.
Overview• Short-term risks• Long-term risks
– Erosion of graft function– Cardiovascular disease– malignancy
• Drug – Drug interactions• Future opportunities
Drug – Drug Infections
A Major Concern!
Reality Check
?ASAMycelex
ViagraGlipizideBactrim
LasixActosVal GCV
LisinoprilPrevacidPrednisone
AtenololFeSO4MMF
NorvascLipitorFK
Clinically relevant drug interactions with immunosuppressive medications
Interacting Agent Effect of Interacting Agent Recommendations/Monitoring
Calcineurin Inhibitors
Antifungals
Anidulafungin No significant effect
Amphotericin B Increased risk of nephrotoxicity Appropriate hydration; monitor renal function closely
Caspofungin Increased hepatic enzymes with cyclosporine
Monitor transaminases closely; Consider alternatives if elevation in hepatic enzymes occurs
Fluconazole Inhibits metabolism Monitor CNI levels closely
Ketoconazole Inhibits metabolism Monitor levels closely; Decrease CNI dose by 50-75%
Micafungin No significant effect
Posaconazole Inhibits metabolism Monitor CNI levels closely; Decrease cyclosporine by 25% and tacrolimus by 66%
Voriconazole Inhibits metabolism Monitor levels closely; Decrease CNI dose by 50-75%
Clinically relevant drug interactions with immunosuppressive medications
Antibiotics
Azithromycin Little effect
Clarithromycin Inhibits metabolism Empiric dose reduction; monitor CNI levels closely
Erythromycin Inhibits metabolism Empiric dose reduction; monitor CNI levels closely
Rifampin Induces metabolism Increase in dose; monitor CNI levels closely
Antiretrovirals
Protease inhibitors Inhibits metabolism Dose reduction; monitor CNI levels closely
Anticonvulsants
Barbiturates Induces metabolism Increase in dose; monitor CNI levels closely
Benzodiazepines No effect
Carbamazepine and Oxcarbazepine
May induce metabolism Monitor CNI levels; may require increase in dose
Levertiracetam No effect
Modafanil Induces metabolism Dose reduction; monitor CNI levels
Phenytoin Induces metabolism Dose reduction; monitor CNI levels closely
Valproic acid No direct effect Monitor levels
Clinically relevant drug interactions with immunosuppressive medications
Antihypertensives
ACEIs/ARBs May increase risk of hyperkalemia Monitor Potassium
Beta-blockers Carvedilol may inhibit Monitor CNI levels
Diltiazem, verapamil, and nifedipine
Inhibit metabolism Decrease CNI dose by 25%; monitor CNI levels closely
Dihydropyridine calcium channel blockers
No effect
Colchicine and NSAIDS
Colchicine Inhibition of colchicine metabolism; competitive inhibition of cyclosporine metabolism
Dose adjustment of colchicine per package labeling required
NSAIDS Increased risk of nephrotoxicity Avoid if possible; use for short period of time if necessary with close monitoring
Lipid Lowering Agents
HMG Co-A reductase inhibitors
Increased statin exposure with cyclosporine No effect with tacrolimus
Significant dose reductions of statin; monitor CPK
Clinically relevant drug interactions with immunosuppressive medications
Lipid Lowering Agents
HMG Co-A reductase inhibitors
Increased statin exposure with cyclosporine No effect with tacrolimus
Significant dose reductions of statin; monitor CPK
Psychiatric Drugs
Citalopram No reports Monitor CNI levels
Desvenlafaxine No reports Caution due to CYP 3A4 metabolism of desvenlafaxine
Duloxetine No reports Monitor CNI levels
Fluvoxamine Inhibits metabolism Monitor CNI levels closely; dose reductions may be necessary
Fluoxetine, paroxetine, and citalopram
Little effect Monitor CNI levels
Haloperidol QT prolongation Monitor QTc interval
Lithium Increased risk of nephrotoxicity Monitor renal function closely
Nefazodone Inhibits metabolism Avoid if possible
Quetiapine and olanzapine QT prolongation Monitor QTc interval
Sertraline May inhibit metabolism Conflicting reports-monitor levels closely
Venlafaxine Little effect Monitor CNI levels
Clinically relevant drug interactions with immunosuppressive medications
AntimetabolitesMMF and MPA
Calcineurin inhibitors
Cyclosporine Reduction in MPA AUC Dose adjustment may be necessary
Antivirals
Acyclovir Possible Increase in AUC Monitor for adverse events
Ganciclovir Decreased clearance of ganciclovir Monitor for adverse events
Gastrointestinal Drugs
Antacids Decrease in AUC and Cmax Avoid concomitant administration if possible
Proton Pump Inhibitors MMF-decrease in Cmax and Tmax MPA—no effect
Caution with MMF
Phosphate Binders
Calcium-free phosphate binders
Decrease in AUC and Cmax Administer 2 hours after MMF
Clinically relevant drug interactions with immunosuppressive medications
Miscellaneous Drugs
Cholestyramine Decrease in AUC Concomitant use not recommended
Oral contraceptives
Decrease in levonorgestrel AUC Caution with levonorgestrel
Anti-infectives
Ciprofloxacin and amoxicillin/clavulanic acid
Decrease in trough levels Caution
Norfloxacin and metronidazole
Decrease in AUC Concomitant use not recommended with combination
Trimethoprin/Sulfamethoxazole
Small reduction in AUC Does not appear clinically significant
Rifampin Increase in exposure Monitor for adverse events
Xanthine Oxidase Inhibitors
Allopurinol Increase in 6-mercaptopurine Avoid concomitant use
Clinically relevant drug interactions with immunosuppressive medications
Mammalian Target of Rapamycin Inhibitors
Calcineurin Inhibitors
Cyclosporine Increase in sirolimus AUC Monitor levels; if given concomitantly, give sirolimus 4 hours after cyclosporine
Antifungals
Ketoconazole Increase in Cmax, Tmax, and AUC
Monitor levels; significant dose reduction required
Voriconazole Increase in Cmax and AUC Monitor levels; significant dose reduction required
Calcium Channel Blockers
Non-dihydropyridine calcium channel blockers
Increase in Cmax and AUC Monitor levels; dose reduction may be required
Antibiotics
Erythromycin Increase in Cmax and AUC Monitor levels; consider azithromycin as an alternative
Rifampin Decrease in Cmax and AUC Monitor levels; significant dose increase required
Antiretrovirals
HIV protease inhibitors Increase in AUC Monitor levels: dose reduction may be required
Improved Graft Survival after Renal Improved Graft Survival after Renal Transplantation in the USTransplantation in the US
Hariharan S, et al. N Eng J Med 2000; 342: 605-612.
19881988 19961996
CRTCRT 7.97.9 13.813.8
LRTLRT 12.712.7 21.621.6
Half Life (Years)Half Life (Years)
PerspectivePerspectiveThe old consideration that control of rejection changes short-term outcomes but not long-term outcomes is not correct.
Kidney transplants should serve their owners for their life expectancy.
Perhaps the biggest problem is:
INADEQUATE FOLLOW-UP AND INADEQUATE FOLLOW-UP AND SURVEILLANCESURVEILLANCE
andand
LACK OF RESPONSE TO CHANGE IN LACK OF RESPONSE TO CHANGE IN FUNCTION!FUNCTION!
Conclusions
• Many kidney transplant patients in general medical practice
• Always work with a transplant center and a nephrologist who is well trained in immunosuppression management
• Many new immunosuppression drugs
• When in doubt, ask for help!