Kidney Transplantation–  Medical, Surgical, and Immunologic Considerations Anil Kapoor, MD, FRCS(C) Associate Professor of...
OBJECTIVES Transplant immunology Acute and Chronic Rejection How does a transplant program work ? Indications for renal tr...
Background DEMOGRAPHICS OF THE TRANSPLANT WAITING LIST TRANSPLANT DONOR & RECIPIENT WORK UP TRANSPLANT SURGERY TRANSPLANT ...
Single kidney transplants by organ source, Canada, 1990-1999   (Number) Source: CORR/CIHI 2001
Comparison of cadaveric organ donation rates, Canada and Provinces, 1998 -2000 (Rate per million population 1 ) 1 Crude ra...
International comparison of cadaveric organ donation rates, 1999 (Rate per million population 1 ) 1 Crude rate.  Sources: ...
Cadaveric donor cause of death, Canada, 1999 1  Includes cerebrovascular accident, ruptured cerebral aneurysm and spontane...
Cadaveric donors by gender and average age, Canada, 1992-1999 Source: CIHI/CORR 2001
Actual cadaveric, potential cadaveric and living organ donors, Provinces, 2000 (Rate per million population 1 ) 1 Crude ra...
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
Bertram L. Kasiske
 
John M. Barry
John M. Barry
John M. Barry
 
 
John M. Barry
John M. Barry
Angelo M. de Mattos
Laurence Chan
 
Laurence Chan
Laurence Chan
Laurence Chan
Laurence Chan
Medical Issues following Renal Transplantation <ul><li>Cardiovascular Disease </li></ul><ul><li>Hypertension </li></ul><ul...
Ischemic Heart Disease After Kidney Transplantation <ul><li>Nature of the Problem </li></ul><ul><li>Registry and retrospec...
Meier-Kriesche  KI April 2001 Cardiovascular Mortality Wait listed vs Transplanted
Event Rates <ul><li>Lindholm 1995: </li></ul><ul><li>-11% of grafts were lost 2-5 yrs post transplant </li></ul><ul><li>-d...
Relative Risk Incident IHD <ul><li>FHS Variables </li></ul><ul><li>Men and Women Surviving > 1 year (n=1124) </li></ul><ul...
Cardiovascular Disease After Renal Transplantation <ul><li>Summary- Kasiske 2000 </li></ul><ul><li>1. Most comprehensive a...
Treatment of Hyperlipidemia <ul><li>General Population </li></ul><ul><li>Meta analysis of statin trials (JAMA 1999;282:234...
Hypertension After Renal Transplantation <ul><li>Causes </li></ul><ul><li>Calcineurin Inhibitors </li></ul><ul><li>Steroid...
Post Transplant Hypertension <ul><li>1. Graded independent relationship between degree of systolic and diastolic hypertens...
Treatment of Post Transplant Hypertension  <ul><li>Calcium channel blockers </li></ul><ul><li>Reduce calcineurin inhibitor...
Prevention of Cardiovascular Disease After Renal  Transplantation <ul><li>Prevention and treatment of diabetes </li></ul><...
Natural History of Bone Loss Following Transplantation Corticosteroid-induced osteoporosis Prednisone dose > 7.5mg / day I...
20 adult LRD renal transplants 11 pre-emptive transplants, 9 transplants 11±22 months on dialysis BMD decreased 6.8% first...
Treatment of Osteoporosis Post Transplant <ul><li>Post menopausal women, patients with osteoporosis or osteopenia should b...
Meier-Kriesche Transplantation 2000 Relative Risk of Infectious Death and Acute Rejection
Connie L. Davis
Connie L. Davis
Connie L. Davis
Medical Management of the Renal Transplant Recipient 2002 -Summary- <ul><li>Cardiovascular Disease remains the major cause...
Medical Management of the Renal Transplant Recipient 2002 -Comments- <ul><li>Care of the renal transplant recipient is bec...
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  • Transplant I and II of 10 Dec 2008 and 04 Mar 2009 by Dr. A ...

    1. 1. Kidney Transplantation– Medical, Surgical, and Immunologic Considerations Anil Kapoor, MD, FRCS(C) Associate Professor of Surgery McMaster University
    2. 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. 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. 4. Single kidney transplants by organ source, Canada, 1990-1999 (Number) Source: CORR/CIHI 2001
    5. 5. Comparison of cadaveric organ donation rates, Canada and Provinces, 1998 -2000 (Rate per million population 1 ) 1 Crude rate Source: CORR/CIHI 2001
    6. 6. International comparison of cadaveric organ donation rates, 1999 (Rate per million population 1 ) 1 Crude rate. Sources: CORR/CIHI 2000; United Network for Organ Sharing (UNOS); Organizacion Nacional de Trasplantes in Spain; Australia & New Zealand Organ Donation Registry.
    7. 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. 8. Cadaveric donors by gender and average age, Canada, 1992-1999 Source: CIHI/CORR 2001
    9. 9. Actual cadaveric, potential cadaveric and living organ donors, Provinces, 2000 (Rate per million population 1 ) 1 Crude rate. Source: CIHI/CORR 2001
    10. 10. Bertram L. Kasiske
    11. 11. Bertram L. Kasiske
    12. 12. Bertram L. Kasiske
    13. 13. Bertram L. Kasiske
    14. 14. Bertram L. Kasiske
    15. 15. Bertram L. Kasiske
    16. 16. Bertram L. Kasiske
    17. 17. Bertram L. Kasiske
    18. 18. Bertram L. Kasiske
    19. 19. Bertram L. Kasiske
    20. 20. Bertram L. Kasiske
    21. 21. Bertram L. Kasiske
    22. 22. Bertram L. Kasiske
    23. 23. Bertram L. Kasiske
    24. 24. Bertram L. Kasiske
    25. 25. Bertram L. Kasiske
    26. 26. Bertram L. Kasiske
    27. 27. Bertram L. Kasiske
    28. 28. Bertram L. Kasiske
    29. 29. Bertram L. Kasiske
    30. 30. Bertram L. Kasiske
    31. 31. Bertram L. Kasiske
    32. 32. Bertram L. Kasiske
    33. 33. Bertram L. Kasiske
    34. 34. Bertram L. Kasiske
    35. 35. Bertram L. Kasiske
    36. 36. Bertram L. Kasiske
    37. 37. Bertram L. Kasiske
    38. 39. John M. Barry
    39. 40. John M. Barry
    40. 41. John M. Barry
    41. 44. John M. Barry
    42. 45. John M. Barry
    43. 46. Angelo M. de Mattos
    44. 47. Laurence Chan
    45. 49. Laurence Chan
    46. 50. Laurence Chan
    47. 51. Laurence Chan
    48. 52. Laurence Chan
    49. 53. Medical Issues following Renal Transplantation <ul><li>Cardiovascular Disease </li></ul><ul><li>Hypertension </li></ul><ul><li>Bone Disease </li></ul><ul><li>Infection and malignancy </li></ul>
    50. 54. Ischemic Heart Disease After Kidney Transplantation <ul><li>Nature of the Problem </li></ul><ul><li>Registry and retrospective studies consistently show </li></ul><ul><li> ~ 4 fold  in major coronary events vs general population </li></ul><ul><li> ~ 2 fold coronary fatality rate vs general population </li></ul><ul><li> reported annual major cardiac event rates vary widely (0.4-3.0%) </li></ul><ul><li>By 15 yrs post transplant 23% rate of IHD, 15% cerebrovascular disease and 15% PVD. </li></ul>
    51. 55. Meier-Kriesche KI April 2001 Cardiovascular Mortality Wait listed vs Transplanted
    52. 56. Event Rates <ul><li>Lindholm 1995: </li></ul><ul><li>-11% of grafts were lost 2-5 yrs post transplant </li></ul><ul><li>-death with function accounts for 49% of graft loss </li></ul><ul><li>- 53% of deaths were due to IHD </li></ul><ul><li>Kasiske 1996: </li></ul><ul><li>-23% of pts have an ischemic event within 15 yrs of transplant . </li></ul>
    53. 57. Relative Risk Incident IHD <ul><li>FHS Variables </li></ul><ul><li>Men and Women Surviving > 1 year (n=1124) </li></ul><ul><li>Variable (%) RR (95% CI) </li></ul><ul><li>Age (yr) 1.06 (1.04-1.08) </li></ul><ul><li>Diabetes* (0.18) 2.78 (1.73-4.49) </li></ul><ul><li>Smoking (0.25) 1.95 (1.20-3.19 ) </li></ul><ul><li>Cholesterol >5.2 (0.77) 2.18 (1.01-4.72) </li></ul><ul><li>BP 140-159 1.68 (0.56-2.55) </li></ul><ul><li>BP >160 1.86 (0.61 -3.55) </li></ul><ul><li>*female diabetic RR 5.40 (2.73-10.66) </li></ul>
    54. 58. Cardiovascular Disease After Renal Transplantation <ul><li>Summary- Kasiske 2000 </li></ul><ul><li>1. Most comprehensive analysis of CV risk after transplantation. </li></ul><ul><li>2. Unusually low event rate and single centre analysis limits the generalizability of the findings. </li></ul><ul><li>3. Older diabetics, especially women, are at highest risk. </li></ul><ul><li>4. Hyperlipidemia and smoking emerge clearly as important risk factors. </li></ul><ul><li>5. Hypertension was not a significant factor contributing to IHD in this population . </li></ul><ul><li>6. Dihydropyridine calcium antagonists and higher CV risk requires further study, particularly with new antihypertensive agents. </li></ul>
    55. 59. Treatment of Hyperlipidemia <ul><li>General Population </li></ul><ul><li>Meta analysis of statin trials (JAMA 1999;282:2340) </li></ul><ul><li>1. 5 RCT’s of 30,817 patients followed for 5.4 years </li></ul><ul><li>2. Treatment  TC 20%,  LDL-C 28%,  TG 13%,  HDL-C 5% </li></ul><ul><li>3. Reduced relative risk for major coronary events (31%) and all cause mortality (21%) </li></ul><ul><li>4. Benefit seen in those with and without a history of heart disease, men and women and both young and older patient </li></ul>
    56. 60. Hypertension After Renal Transplantation <ul><li>Causes </li></ul><ul><li>Calcineurin Inhibitors </li></ul><ul><li>Steroids </li></ul><ul><li>Renal Dysfunction </li></ul><ul><li>RAS </li></ul><ul><li>Native Kidneys </li></ul><ul><li>Essential Hypertension etc </li></ul>
    57. 61. Post Transplant Hypertension <ul><li>1. Graded independent relationship between degree of systolic and diastolic hypertension and graft loss. </li></ul><ul><li>2. Relationship persists when patient death is either considered graft loss, or is censored. </li></ul><ul><li>3. Independent association between blood pressure control at 1 year and all cause mortality . </li></ul><ul><li>4. Kasiske’s data fails to demonstrate an association between HTN and atherosclerotic disease. </li></ul>
    58. 62. Treatment of Post Transplant Hypertension <ul><li>Calcium channel blockers </li></ul><ul><li>Reduce calcineurin inhibitor induced afferent arteriolar vasoconstriction and may reduce nephrotoxicity. </li></ul><ul><li>JASN 1999 : nifedipine resulted in improved renal function compared to lisinopril with equivalent BP control. </li></ul><ul><li>Ace inhibitors </li></ul><ul><li>Reduce proteinuria (compared to betablocker Hypertension 1999 ). </li></ul><ul><li>Reduce post transplant erythrocytosis. </li></ul>
    59. 63. Prevention of Cardiovascular Disease After Renal Transplantation <ul><li>Prevention and treatment of diabetes </li></ul><ul><li>Smoking cessation </li></ul><ul><li>Aggressive lipid control - our current target for >1 risk factor is LDL<2.5 </li></ul><ul><li>Treatment of hypertension (LVH / CHF / graft dysfunction) </li></ul><ul><li>ASA and other anti-platelet agents </li></ul><ul><li>Further information on risk factor modification is required for the renal transplant population. </li></ul>
    60. 64. Natural History of Bone Loss Following Transplantation Corticosteroid-induced osteoporosis Prednisone dose > 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.
    61. 65. 20 adult LRD renal transplants 11 pre-emptive transplants, 9 transplants 11±22 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. Bone Loss - Julian et al, NEJM 1991
    62. 66. Treatment of Osteoporosis Post Transplant <ul><li>Post menopausal women, patients with osteoporosis or osteopenia should be considered for bisphosphonate therapy (treatment and prophylaxis) when starting prednisone. </li></ul><ul><li>Patients who will receive very high dose steroids should be considered for prophylaxis. </li></ul><ul><li>Patients with normal baseline bone density should be considered for therapy with calcitriol. </li></ul>
    63. 67. Meier-Kriesche Transplantation 2000 Relative Risk of Infectious Death and Acute Rejection
    64. 68. Connie L. Davis
    65. 69. Connie L. Davis
    66. 70. Connie L. Davis
    67. 71. Medical Management of the Renal Transplant Recipient 2002 -Summary- <ul><li>Cardiovascular Disease remains the major cause of morbidity and mortality following transplantation. </li></ul><ul><li>The traditional risk factors for CVD do not apply to this population in the same way that they do for the general population. </li></ul><ul><li>We have reasonable strategies for bone disease following transplantation. </li></ul><ul><li>Over immunosuppression in the elderly leads to increased morbidity due to infection and perhaps malignancy. </li></ul>
    68. 72. Medical Management of the Renal Transplant Recipient 2002 -Comments- <ul><li>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. </li></ul><ul><li>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. </li></ul>
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