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Kidney Transplantation

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Title: Kidney Transplantation


1
Kidney Transplantation Medical, Surgical, and
Immunologic Considerations
  • Anil Kapoor, MD, FRCS(C)
  • Associate Professor of Surgery
  • McMaster University

2
OBJECTIVES
Transplant immunology Acute and Chronic
Rejection How does a transplant program work
? Indications for renal transplant Patient
selection Technical/ Surgical considerations in
renal transplant
3
Background
DEMOGRAPHICS OF THE TRANSPLANT WAITING
LIST TRANSPLANT DONOR RECIPIENT WORK
UP TRANSPLANT SURGERY TRANSPLANT IMMUNOLOGY (
REJECTION ) POST TRANSPLANT ISSUES HLA/ CROSS
MATCH
4
Single kidney transplants by organ source,
Canada, 1990-1999 (Number)
Source CORR/CIHI 2001
5
Comparison of cadaveric organ donation rates,
Canada and Provinces, 1998 -2000 (Rate per
million population1)
1Crude rate Source CORR/CIHI 2001
6
International comparison of cadaveric organ
donation rates, 1999 (Rate per million
population1)
1Crude rate. Sources CORR/CIHI 2000 United
Network for Organ Sharing (UNOS) Organizacion
Nacional de Trasplantes in Spain Australia New
Zealand Organ Donation Registry.
7
Cadaveric donor cause of death, Canada, 1999
1 Includes cerebrovascular accident, ruptured
cerebral aneurysm and spontaneous cerebral
haemorrhage. 2 Motor vehicle collision Source
CIHI/CORR 2001
8
Cadaveric donors by gender and average age,
Canada, 1992-1999
Source CIHI/CORR 2001
9
Actual cadaveric, potential cadaveric and living
organ donors, Provinces, 2000 (Rate per million
population1)
1Crude rate. Source CIHI/CORR 2001
10
Bertram L. Kasiske
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Bertram L. Kasiske
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Bertram L. Kasiske
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Bertram L. Kasiske
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John M. Barry
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John M. Barry
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John M. Barry
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John M. Barry
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John M. Barry
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Angelo M. de Mattos
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Laurence Chan
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Laurence Chan
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Laurence Chan
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Laurence Chan
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Laurence Chan
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Medical Issues following Renal Transplantation
  • Cardiovascular Disease
  • Hypertension
  • Bone Disease
  • Infection and malignancy

54
Ischemic Heart DiseaseAfter Kidney
Transplantation
  • Nature of the Problem
  • Registry and retrospective studies consistently
    show
  • ? 4 fold ? in major coronary events vs general
    population
  • ? 2 fold coronary fatality rate vs general
    population
  • ? reported annual major cardiac event rates vary
    widely (0.4-3.0)
  • By 15 yrs post transplant 23 rate of IHD, 15
    cerebrovascular disease and 15 PVD.

55

Meier-Kriesche KI April 2001Cardiovascular
Mortality Wait listed vs Transplanted

56
Event Rates
  • Lindholm 1995
  • -11 of grafts were lost 2-5 yrs post transplant
  • -death with function accounts for 49 of graft
    loss
  • -53 of deaths were due to IHD
  • Kasiske 1996
  • -23 of pts have an ischemic event within 15 yrs
    of transplant.

57
Relative Risk Incident IHD
  • FHS Variables
  • Men and Women Surviving gt 1 year (n1124)
  • Variable () RR (95 CI)
  • Age (yr) 1.06 (1.04-1.08)
  • Diabetes (0.18) 2.78 (1.73-4.49)
  • Smoking (0.25) 1.95 (1.20-3.19)
  • Cholesterol gt5.2 (0.77) 2.18 (1.01-4.72)
  • BP 140-159 1.68 (0.56-2.55)
  • BP gt160 1.86 (0.61 -3.55)
  • female diabetic RR 5.40 (2.73-10.66)

58
Cardiovascular DiseaseAfter Renal Transplantation
  • Summary- Kasiske 2000
  • 1. Most comprehensive analysis of CV risk after
    transplantation.
  • 2. Unusually low event rate and single centre
    analysis limits the generalizability of the
    findings.
  • 3. Older diabetics, especially women, are at
    highest risk.
  • 4. Hyperlipidemia and smoking emerge clearly as
    important risk factors.
  • 5. Hypertension was not a significant factor
    contributing to IHD in this population.
  • 6. Dihydropyridine calcium antagonists and higher
    CV risk requires further study, particularly with
    new antihypertensive agents.

59
Treatment of Hyperlipidemia
  • General Population
  • Meta analysis of statin trials (JAMA
    19992822340)
  • 1. 5 RCTs of 30,817 patients followed for 5.4
    years
  • 2. Treatment ? TC 20, ? LDL-C 28, ? TG 13, ?
    HDL-C 5
  • 3. Reduced relative risk for major coronary
    events (31) and all cause mortality (21)
  • 4. Benefit seen in those with and without a
    history of heart disease, men and women and both
    young and older patient

60
Hypertension After RenalTransplantation
  • Causes
  • Calcineurin Inhibitors
  • Steroids
  • Renal Dysfunction
  • RAS
  • Native Kidneys
  • Essential Hypertension etc

61
Post Transplant Hypertension
  • 1. Graded independent relationship between degree
    of systolic and diastolic hypertension and graft
    loss.
  • 2. Relationship persists when patient death is
    either considered graft loss, or is censored.
  • 3. Independent association between blood pressure
    control at 1 year and all cause mortality .
  • 4. Kasiskes data fails to demonstrate an
    association between HTN and atherosclerotic
    disease.

62
Treatment of Post Transplant Hypertension
  • Calcium channel blockers
  • Reduce calcineurin inhibitor induced afferent
    arteriolar vasoconstriction and may reduce
    nephrotoxicity.
  • JASN 1999 nifedipine resulted in improved
    renal function compared to lisinopril with
    equivalent BP control.
  • Ace inhibitors
  • Reduce proteinuria (compared to betablocker
    Hypertension 1999).
  • Reduce post transplant erythrocytosis.

63
Prevention of CardiovascularDisease After Renal
Transplantation
  • Prevention and treatment of diabetes
  • Smoking cessation
  • Aggressive lipid control - our current target for
    gt1 risk factor is LDLlt2.5
  • Treatment of hypertension (LVH / CHF / graft
    dysfunction)
  • ASA and other anti-platelet agents
  • Further information on risk factor modification
    is required for the renal transplant population.

64
Natural History of Bone Loss Following
Transplantation

Corticosteroid-induced osteoporosis Prednisone
dose gt 7.5mg / day In non-transplant
populations the rate of bone loss due to
corticosteroids is 3 - 4 over one year ( NEJM
1997 ). Renal transplant recipients lose 7 - 10
of BMD in the first year, and 1 -2 per year
thereafter.
65

Bone Loss - Julian et al, NEJM 1991
20 adult LRD renal transplants 11 pre-emptive
transplants, 9 transplants 1122 months on
dialysis BMD decreased 6.8 first 6 months, then
2.6 in the subsequent 12 months Biopsies showed
resolution of secondary hyperparathyroidism , and
a reduction in the amount of bone replaced during
each remodelling cycle. We now recognize this
bone loss to be predominanty due to the effects
of corticosteroids on bone.

66
Treatment of Osteoporosis Post Transplant
  • Post menopausal women, patients with osteoporosis
    or osteopenia should be considered for
    bisphosphonate therapy (treatment and
    prophylaxis) when starting prednisone.
  • Patients who will receive very high dose steroids
    should be considered for prophylaxis.
  • Patients with normal baseline bone density should
    be considered for therapy with calcitriol.

67

Meier-Kriesche Transplantation 2000Relative Risk
of Infectious Death and Acute Rejection
68
Connie L. Davis
69
Connie L. Davis
70
Connie L. Davis
71
Medical Management of the Renal Transplant
Recipient 2002-Summary-
  • Cardiovascular Disease remains the major cause of
    morbidity and mortality following
    transplantation.
  • The traditional risk factors for CVD do not
    apply to this population in the same way that
    they do for the general population.
  • We have reasonable strategies for bone disease
    following transplantation.
  • Over immunosuppression in the elderly leads to
    increased morbidity due to infection and perhaps
    malignancy.

72
Medical Management of the Renal Transplant
Recipient 2002-Comments-
  • Care of the renal transplant recipient is
    becoming less an issue of adequate
    immunosuppression and more an issue of CKD in
    the face of drugs which worsen many medical
    conditions.
  • We recognize the efforts of primary nephrologists
    and the multidisciplinary teams that they work
    with, in preparing patients for renal transplant
    and following their medical course following
    transplantation.
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