Clinical Care of Renal Transplant Recipients: An Internist’s Guide

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




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




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).

http://jasn.asnjournals.org/content/vol17/issue3/images/large/asn0030606820001.jpeg

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).

http://jasn.asnjournals.org/content/vol17/issue3/images/large/asn0030606820003.jpeg

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.




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%


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


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


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


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


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


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!