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Author(s): Silas P. Norman, M.D., 2009

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Transplant
            Epidemiology
             Silas P. Norman M.D.
              Assistant Professor
             Transplant Nephrology

Fall 2008
Learning Objectives
•  To understand kidney transplantation
   as superior to other forms of renal
   replacement therapy (RRT)
•  To understand the advantages of living
   kidney donation
•  To understand kidney transplantation
   as cost-effective over dialysis
Introduction
•  Over 100,000 individuals in the U.S. develop
   end-stage kidney disease (ESRD) every year

•  In the U.S., Diabetes (DM) and Hypertension
   (HTN) are most common causes of ESRD

•  The prevalence of both DM and HTN are
   increasing leading to an epidemic of ESRD

•  Kidney transplantation is a form of RRT that
   improves survival and quality of life in the ESRD
   population
Prevalent Counts and
Rates of ESRD in the U.S.




U.S. Renal Data System, ADR 2005
Risk for All-Cause Death in
     ESRD by Modality




U.S. Renal Data System, ADR 2005
Transplant Demographics
~70,000 patients on deceased donor waiting
  list. They are disproportionately African-
  American, Hispanic and female
~25,000 added yearly
~3,500 die on waiting list annually without
  getting a transplant offer
~1,000 annually are removed from list b/c they
  are too sick to transplant
~9000 patients transplanted from list annually
Sources of Donors
•  Living Donors:
  –  Living Related (LRD)
  –  Living Unrelated (LURD)

•  Deceased Donors:
  –  Standard Criteria (SCD)
  –  Extended Criteria (ECD)
  –  Deceased Cardiac Death (DCD)
Living Donor Selection
•  Selection bias towards protecting donor
   candidate
•  Living donors must be altruistic and be
   healthy
•  Living donor contraindications:
  –  Diabetes Mellitus (Type 1, Type 2 or gestational*)
  –  Hypertension (BP > 140/90)
  –  Active malignancies, infections or substance abuse
  –  Donor age < 18 or > 60
  *Can make exception if gestational DM long ago and candidate is not currently
    diabetic
Advantages of Living vs.
Deceased Donor Transplantation

  •    Pre-emptive transplantation
  •    Less rejection
  •    Better graft function
  •    Longer graft survival
Deceased Donors
Standard Criteria Donor (SCD)
•  Age < 60
•  No known kidney or vascular disease
•  Brain Death – due to trauma, anoxia,
   stroke
•  Diagnosis:
  –  Unresponsive
  –  Apneic
  –  EEG or blow flow study
Deceased Donors
    Extended Criteria Donors
             (ECD)
•  All donors age > 60 regardless of co-
   morbidities
•  Donors between the ages of 50-59 who have
   at least 2 of the 3 following criteria:
  –  Stroke
  –  Hypertension
  –  Serum creatinine >1.5
•  Generally still brain dead donors
Deceased Donors
Deceased Cardiac Death (DCD)

•  Cardiac death (on life support), but not
   brain dead
  –  No chance of recovery
  –  Family decides to withdrawal life support
  –  Physician caring for patient declares them
     dead
  –  Wait 5 minutes and proceed with donation
Deceased Donor Kidney
       Allocation
•  Waiting time
     –  From time of acceptance at a transplant
        center
•    Matching
•    Panel Reactive Antibodies > 80%
•    Pediatric candidate
•    Prior living kidney donor
Number of Transplants/Year
     by Donor Type




    U.S. Renal Data System, ADR 2005
Recipient Selection
•  Selection criteria
    –  Bias toward offering transplant when possible
    –  Standard of care for all causes of ESRD
•  Contraindications
    –  Severe coronary artery disease not amenable to
       intervention
    –  Severe peripheral vascular occlusive disease
    –  Severe pulmonary disease
    –  Active malignancies or infections
    –  Non-adherence to medical regimen
    –  Severe obesity or malnutrition
Advantages of Kidney
      Transplantation
•  Improved patient survival

•  Improved quality of life

•  Cost effective
Outcomes of Kidney
     Transplantation
•  One year patient survival > 95%
•  One year living donor graft survival
   about 95%
•  One year deceased donor graft survival
   85-90%
•  Transplant half-lives (years)
  –  Living: ~20yrs
  –  Deceased: ~10yrs
Survival With Different
    Forms of RRT
Survival After Kidney
                  Transplant




NEJM, 1999
Causes of Death After
        Kidney Transplant
                          11.3%
 30.3%                       6.9%         MI
                                          Stroke
                                          Other Cardiac
                                          Tumors
                                  21.9%
                                          Infection
                                          Other
      17.8%
                         11.9%


U.S. Renal Data System
Renal Allograft Survival
                                   by Donor Type
                               100                    94
% Probability of Survival




                                                                   85.8
                                                                              77.4
                                  80                  88.3                           Living Donor
                                                                   73.4
                                  60                                                 Cadaveric
                                                                              62.7
                                                                                     Donor
                                  40

                                  20

                                      0
                                            0          1     2      3     4    5
                                                                 Years
                            1999 UNOS Annual Report
Annual Cost of ESRD to
       Medicare
Annual Cost of ESRD




Source Undetermined
Annual Cost of RRT by
             Modality




Source Undetermined
Disadvantages of Kidney
    Transplantation
•  Organ shortage leads to long wait times
   on the deceased donor list
•  Morbidity associated with operation
•  Negative effects of Immunosuppression
  –  Cardiovascular disease
  –  Infection
  –  Malignancy
  –  Bone disease
Pancreas Transplantation
•  10% of kidney transplant recipients
•  Indications
    –  ESRD from type 1 diabetes mellitus
    –  Hypoglycemic unawareness
•  Types
    –  Simultaneous kidney and pancreas (SPK)
    –  Living kidney followed by pancreas (PAK)
    –  Pancreas transplant alone (PTA)
Risk and Benefits of
Pancreas Transplantation
•  Risks
    –  Increased risk of surgical complications
    –  Increased incidence of infection
    –  Potential for pancreas allograft rejection and
       pancreatitis
•  Benefits
    –  Protection from hypoglycemia
    –  Freedom from insulin, diabetic diet, glucose
       monitoring
    –  Stabilization of retinopathy, neuropathy
    –  Reduced future diabetic nephrosclerosis
    –  Improved survival?
Results of Pancreas
Transplantation
•  One-year patient survival > 95%
•  One-year pancreas transplant survival
  – SPK 90%
  – PAK 76%
  – PTA 72%
•  One-year kidney graft survival with SPK 91%
•  Ten-year SPK patient survival 67%
Additional Source Information
                          for more information see: http://open.umich.edu/wiki/CitationPolicy

Slide 6: U.S. Renal Data System, ADR 2005, http://www.usrds.org/
Slide 7: U.S. Renal Data System, ADR 2005, http://www.usrds.org/
Slide 16: U.S. Renal Data System, ADR 2005, http://www.usrds.org/
Slide 21: NEJM, 1999
Slide 22: U.S. Renal Data System, http://www.usrds.org/
Slide 23: 1999 UNOS Annual Report
Slide 25: Source Undetermined
Slide 26: Source Undetermined

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10.07.08(b): Transplant Epidemiology

  • 1. Author(s): Silas P. Norman, M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution–Noncommercial–Share Alike 3.0 License: http://creativecommons.org/licenses/by-nc-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  • 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  • 3. Transplant Epidemiology Silas P. Norman M.D. Assistant Professor Transplant Nephrology Fall 2008
  • 4. Learning Objectives •  To understand kidney transplantation as superior to other forms of renal replacement therapy (RRT) •  To understand the advantages of living kidney donation •  To understand kidney transplantation as cost-effective over dialysis
  • 5. Introduction •  Over 100,000 individuals in the U.S. develop end-stage kidney disease (ESRD) every year •  In the U.S., Diabetes (DM) and Hypertension (HTN) are most common causes of ESRD •  The prevalence of both DM and HTN are increasing leading to an epidemic of ESRD •  Kidney transplantation is a form of RRT that improves survival and quality of life in the ESRD population
  • 6. Prevalent Counts and Rates of ESRD in the U.S. U.S. Renal Data System, ADR 2005
  • 7. Risk for All-Cause Death in ESRD by Modality U.S. Renal Data System, ADR 2005
  • 8. Transplant Demographics ~70,000 patients on deceased donor waiting list. They are disproportionately African- American, Hispanic and female ~25,000 added yearly ~3,500 die on waiting list annually without getting a transplant offer ~1,000 annually are removed from list b/c they are too sick to transplant ~9000 patients transplanted from list annually
  • 9. Sources of Donors •  Living Donors: –  Living Related (LRD) –  Living Unrelated (LURD) •  Deceased Donors: –  Standard Criteria (SCD) –  Extended Criteria (ECD) –  Deceased Cardiac Death (DCD)
  • 10. Living Donor Selection •  Selection bias towards protecting donor candidate •  Living donors must be altruistic and be healthy •  Living donor contraindications: –  Diabetes Mellitus (Type 1, Type 2 or gestational*) –  Hypertension (BP > 140/90) –  Active malignancies, infections or substance abuse –  Donor age < 18 or > 60 *Can make exception if gestational DM long ago and candidate is not currently diabetic
  • 11. Advantages of Living vs. Deceased Donor Transplantation •  Pre-emptive transplantation •  Less rejection •  Better graft function •  Longer graft survival
  • 12. Deceased Donors Standard Criteria Donor (SCD) •  Age < 60 •  No known kidney or vascular disease •  Brain Death – due to trauma, anoxia, stroke •  Diagnosis: –  Unresponsive –  Apneic –  EEG or blow flow study
  • 13. Deceased Donors Extended Criteria Donors (ECD) •  All donors age > 60 regardless of co- morbidities •  Donors between the ages of 50-59 who have at least 2 of the 3 following criteria: –  Stroke –  Hypertension –  Serum creatinine >1.5 •  Generally still brain dead donors
  • 14. Deceased Donors Deceased Cardiac Death (DCD) •  Cardiac death (on life support), but not brain dead –  No chance of recovery –  Family decides to withdrawal life support –  Physician caring for patient declares them dead –  Wait 5 minutes and proceed with donation
  • 15. Deceased Donor Kidney Allocation •  Waiting time –  From time of acceptance at a transplant center •  Matching •  Panel Reactive Antibodies > 80% •  Pediatric candidate •  Prior living kidney donor
  • 16. Number of Transplants/Year by Donor Type U.S. Renal Data System, ADR 2005
  • 17. Recipient Selection •  Selection criteria –  Bias toward offering transplant when possible –  Standard of care for all causes of ESRD •  Contraindications –  Severe coronary artery disease not amenable to intervention –  Severe peripheral vascular occlusive disease –  Severe pulmonary disease –  Active malignancies or infections –  Non-adherence to medical regimen –  Severe obesity or malnutrition
  • 18. Advantages of Kidney Transplantation •  Improved patient survival •  Improved quality of life •  Cost effective
  • 19. Outcomes of Kidney Transplantation •  One year patient survival > 95% •  One year living donor graft survival about 95% •  One year deceased donor graft survival 85-90% •  Transplant half-lives (years) –  Living: ~20yrs –  Deceased: ~10yrs
  • 20. Survival With Different Forms of RRT
  • 21. Survival After Kidney Transplant NEJM, 1999
  • 22. Causes of Death After Kidney Transplant 11.3% 30.3% 6.9% MI Stroke Other Cardiac Tumors 21.9% Infection Other 17.8% 11.9% U.S. Renal Data System
  • 23. Renal Allograft Survival by Donor Type 100 94 % Probability of Survival 85.8 77.4 80 88.3 Living Donor 73.4 60 Cadaveric 62.7 Donor 40 20 0 0 1 2 3 4 5 Years 1999 UNOS Annual Report
  • 24. Annual Cost of ESRD to Medicare
  • 25. Annual Cost of ESRD Source Undetermined
  • 26. Annual Cost of RRT by Modality Source Undetermined
  • 27. Disadvantages of Kidney Transplantation •  Organ shortage leads to long wait times on the deceased donor list •  Morbidity associated with operation •  Negative effects of Immunosuppression –  Cardiovascular disease –  Infection –  Malignancy –  Bone disease
  • 28. Pancreas Transplantation •  10% of kidney transplant recipients •  Indications –  ESRD from type 1 diabetes mellitus –  Hypoglycemic unawareness •  Types –  Simultaneous kidney and pancreas (SPK) –  Living kidney followed by pancreas (PAK) –  Pancreas transplant alone (PTA)
  • 29. Risk and Benefits of Pancreas Transplantation •  Risks –  Increased risk of surgical complications –  Increased incidence of infection –  Potential for pancreas allograft rejection and pancreatitis •  Benefits –  Protection from hypoglycemia –  Freedom from insulin, diabetic diet, glucose monitoring –  Stabilization of retinopathy, neuropathy –  Reduced future diabetic nephrosclerosis –  Improved survival?
  • 30. Results of Pancreas Transplantation •  One-year patient survival > 95% •  One-year pancreas transplant survival – SPK 90% – PAK 76% – PTA 72% •  One-year kidney graft survival with SPK 91% •  Ten-year SPK patient survival 67%
  • 31. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 6: U.S. Renal Data System, ADR 2005, http://www.usrds.org/ Slide 7: U.S. Renal Data System, ADR 2005, http://www.usrds.org/ Slide 16: U.S. Renal Data System, ADR 2005, http://www.usrds.org/ Slide 21: NEJM, 1999 Slide 22: U.S. Renal Data System, http://www.usrds.org/ Slide 23: 1999 UNOS Annual Report Slide 25: Source Undetermined Slide 26: Source Undetermined