Kidney Transplantation

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Kidney Transplantation Medical, Surgical, and
Immunologic Considerations

• Anil Kapoor, MD, FRCS(C)
• Associate Professor of Surgery
• McMaster University

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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
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Background
DEMOGRAPHICS OF THE TRANSPLANT WAITING
LIST TRANSPLANT DONOR RECIPIENT WORK
UP TRANSPLANT SURGERY TRANSPLANT IMMUNOLOGY (
REJECTION ) POST TRANSPLANT ISSUES HLA/ CROSS
MATCH
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Single kidney transplants by organ source,
Canada, 1990-1999 (Number)
Source CORR/CIHI 2001
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Comparison of cadaveric organ donation rates,
Canada and Provinces, 1998 -2000 (Rate per
million population1)
1Crude rate Source CORR/CIHI 2001
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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.
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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
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Cadaveric donors by gender and average age,
Canada, 1992-1999
Source CIHI/CORR 2001
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Actual cadaveric, potential cadaveric and living
organ donors, Provinces, 2000 (Rate per million
population1)
1Crude rate. Source CIHI/CORR 2001
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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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Angelo M. de Mattos
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Medical Issues following Renal Transplantation

• Cardiovascular Disease
• Hypertension
• Bone Disease
• Infection and malignancy

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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.

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

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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.

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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)

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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.

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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

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Hypertension After RenalTransplantation

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

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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.

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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.

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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.

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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.
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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.

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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.

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Meier-Kriesche Transplantation 2000Relative Risk
of Infectious Death and Acute Rejection
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Connie L. Davis
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Connie L. Davis
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Connie L. Davis
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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.

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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.