The Donor Shortage: Year 54

1
The Donor ShortageYear 54
2
Number of Kidney Transplants vs Waiting List
3
Transplants Done
4

• Living Donors

5
Should we use living donors at all?

• Primum no Nocere
• First do no harm
• Not really Hippocrates (Thomas Sydenham)

6

• We also treat the Human Spirit
• Loyola
• Benefits to the living donor are in the spiritual
  realm.
• Donor nephrectomy the operation that treats the
  human spirit (Human body not so much)

7
History of Living Donors

• 1954 Identical Twin Transplants
• 1961 first transplant done using azathioprine.
  Move beyond identical twins siblings, parents,
  children
• 1982 Cyclosporine makes HLA matching less
  important unrelated donors and distant relatives
• Efforts to transplant ABO incompatible donors
  recipient pairs

8
Living Donor TransplantsUSA 1988 to May 2008

• Total Number Peak year
• Total 91,536 2004
• Kidney 87,577 2005
• Liver 3,565 2001
• Lung 249 1998-1999
• Pancreas/KP 70 1996
• Intestine 35 2005
• UNOS Data base

9
Living Donors Peak vs Current

• Total Peak 2007
• Total 91,536 6,991 6,307
• Kidney 87,577 6,647 6,037
• Liver 3,565 522 266
• Lung 249 29 3
• Pancreas/KP 70 11 0
• Intestine 35 6 1
• UNOS Data Base

10
Criteria for A Living Donor

• Is she willing to donate?
• Can she get through surgery?
• Can she live in good health with one kidney?
• Does she have any infection or cancer that could
  be transmitted to the recipient

11
Which Presidential Candidates Can Donate a Kidney

• Yes
• Barak Obama
• Hillary Clinton
• George Bush
• No
• John McCain
• Dick Cheney
• John Kerry
• John Edwards

12
Living Donor NephrectomyUSA 1999-2001 N 10,828

• Open 52.3
• Hand Assisted Laparoscopic 20.7
• Laparoscopic 27

13
Risks of Donor NephrectomyImmediate RisksUSA
1999-2001 10,828

• Open HALN LN
• Death 0 0 2(3)(1/1461)
• Reoperation 22 (0.4) 23 (1) 21( 0.9)
• Readmission 0.6 1.6
• Other Comp 0.3 1.0 0.8
• Amsterdam Forum

14
Complications of Donor NephrectomyImmediate
Operative Risk

• Death 0.03
• Pneumothorax 1.5
• Wound Infection 2.5
• Urinary Tract Infection 0.3
• Myocardial Infarction Rare
• Pulmonary Embolus Rare
• Financial Hardship 23
• Johnson et al. Transplantation 641124-1128, 1997

15
Other Rare Complications

• Acute Renal Failure
• Chylous acites
• Splenic laceration

16
Risks of Donor NephrectomyLong-Term

• Renal Failure 0.1
• Proteinuria (150 mg/24 hrs) 17
• Hypertension 25
• Change in Employment 3.8
• Problems Obtaining Life/ Health Insurance 4.2
• Problems Obtaining Disability Insurance 2.3

17
Living Donor Events to be Reported

• Donor death
• Return to the OR in the post op period
• Readmission to the hospital within 6 months
• Organ failure

18
Renal Failure in Kidney Donors

• Renal Function and Renal Failure
• GFR is 70-90 ml/min post donation
• 9-12 have 50 drop in GFR at 10 yrs
• ESRD 0.04 vs 0.03 for population
• 56 previous living donors with ESRD from UNOS
  data base. 50,000 living donors

19
Renal Failure in Living Donors

• If only 56 donors have reached end stage renal
  disease, why have I seen 9 of them?
• Is this under reported?

20
New Potential Living Donors

• High Risk Donors
• Living Unrelated Donors
• Paid Donors and Donors Receiving Non Monetary
  Rewards
• Donor Exchange

21
High Risk Living Donors

• Hypertension controlled with one medication
• Donors with decreased renal function
• Kidney Stones
• Family History of Diabetes
• Obese donors
• Older Donors (oldest living donor was 81 yrs)

22
Obesity

• Most programs have a cut off between 30 and 35
  BMI for donors.
• Obese donors dont have lower corrected GFR at
  follow-up

23
Donor Renal Function

• Corrected GFR of 80 cc/min (radioisotope GFR is
  ideal)
• 20 of center accept down to 60 cc, min
• No widely used test for renal reserve (pregnancy)

24
Donor Hypertension

• No consensus
• Many centers accept patients on one medication
• Should donor hypertension be treated differently
  in black and white donors
• Motivated donors can take BP meds and not report
  it

25
Donor Hypertension

• 18 Hypertensive donors
• GFR at 7 years post donation 71 cc/min
• 75 normotensive donors
• GFR at 7 years follow-up 75 cc/min
• Gil Theil, Amsterdam Forum

26
Proteinuria

• 300 mg contraindicates transplant
• Microalbumin

27
Hematuria

• Patient should have a urologic work up
• Patient with dysmorphic red cell should undergo
  biopsy
• IgA nephropathy found in 16 of donors in Japan
  (living and deceased)

28
Stones

• Single stone past or current
• Exclusions
• Nephrocalcinosis
• Recurrence on treatment
• Cystinuria or hyperoxaluria
• Inflammatory bowel disease

29
Cancer

• Exclusion History of melanoma, breast cancer,
  testicular cancer, choriocarcinoma, heme cancers,
  monoclonal gamopathy
• Current cancer low grade non melanoma skin
  cancer
• Colon Ca Dukes class A. More than 5 years out is
  ok

30
Infections

• HIV
• Hepatitis C
• Hepatitis B (core antibody positive to surface
  antibody positive recipient)
• Syphilis
• TB (Treated TB not an exclusion)
• Chagas Disease

31
Screening for InfectionsLocal Custom

• Malaria
• Schistosomiasis
• Human Herpes Virus 8
• Strongyloides
• Brucellosis
• Mad Cow Disease

32
West Nile Virus

• Deceased donors are not screened because of the
  high false positive rate
• We have tested donors covered with mosquito bites

33
Living Unrelated Donors

• If you believe in the brotherhood of
• man, there are no unrelated donors

34

• Self sacrifice enables you to sacrifice others
  without blushing
• George Bernard Shaw Man and Superman

35
Donor Recipient Relationship
Unos Database
36
Donor Recipient Relationship USA

• Year 1988 2007
• Parent 282 657
• Child 157 982
• Sibling 957 1445
• Spouse 38 793
• Living Unrelated Donor 25 1245
• Distant Relative 36 481
• Altruistic 1 97
• Half Sibling 2 64
• Identical Twin 1 15
• Living Donor Exchange 0 126
• LD-DD Exchange 0 88
• UNOS Database

37
Change from 2005

• Increased
• Altruistic
• Living donor paired exchange
• Living donor deceased donor paired exchange
• Decreased
• Parents, children, siblings, spouses, unrelated
  donors, distant relatives

38
Unrelated DonorsLoyola

• 15.6 of all donors 30.7 of living donors
• Wife 19
• Husband 9
• Friend 15
• Friend from church 4
• Fianceé 3
• Sister-in-law 4
• Altruistic 2
• Step daughter 2
• Brotherin-law 2

39
Unrelated DonorsLoyola

• Friends wife 1
• Wifes friend 1
• Wifes cousin 2
• Husbands cousin 1
• God daughter 1
• Step Mother 1
• Wifes employee 1
• Girlfriends Father 1
• Ex boy friend 1
• Ex husbands new wife 1

40
Survey of Attitudes toward Directed Altruistic
Donation1028 respondents

• Would you donate a kidney to a stranger for no
  payment?
• Yes 26
• Probably yes 20
• No 28
• Probably no 21
• Dont know 5
• Spital,A Transplantation vol 761252-1256, 2005

41
Survey of Attitudes toward Directed Altruistic
Donation1028 respondents

• Should altruistic donors be allowed to select a
  specific recipient?
• Yes 26
• Probably yes 21
• No 36
• Probably no 14
• Dont know 3
• Spital,A Transplantation vol 761252-1256, 2005

42
Survey of Attitudes toward Directed Altruistic
Donation1021 respondents

• Should the donor be allowed to direct donation
  to a
• Yes No Unsure
• Child 74 22 4
• Specific race 28 68 4
• Specific religion 30 65 4
• Someone who 43 51 6
• advertised
• Spital,A Transplantation vol 761252-1256, 2005

43
Public Solicitation of Organs

• Favors the person with knowledge of the media
• Favors celebrity
• Financial advantage MatchingDonors.com lists
  potential recipients for a fee (295/month)
• MatchingDonors.com 5022 potential donors listed
• Possibility of financial consideration after the
  fact

44
Under Age Donors

• 48 Donors in the United States donating between
  1988 and 2007 were 17 years of age or under

45
Under Age Donors

• There has to be an age limit. I dont think you
  can make a decision like this until you are at
  least nine
• Michael Molitch-Hou, age 13

46
Proposed UNOS Exclusionsfor Donors

• Under Age 18
• Hypertension 130/90 for donors under 50
• Diabetic
• BMI 35
• Coronary Artery Disease, Chronic lung disease
• Kidney Function below a certain level
• Uncontrolled psychiatric illness

47

• Should we allow living donors to sell their
  kidneys?
• This practice is currently illegal in many
  countries but does happen anyway.

48
National Organ Transplant Act1984

• It shall be unlawful for any person to knowingly
  acquire, receive or otherwise transfer any human
  organ for valuable consideration for use in human
  transplantation if it affects interstate
  commerce.
• Fine of 50,000
• Five years in jail

49
Opposition to Paid Donation

• Ethics committee of the transplantation Society
• World Health Organization
• John Paul II

50
Other Sales

• Sperm donors
• Egg Donors
• Surrogate Mothers

51
Objections to Paid Donation

• Commercialization will erode the good will built
  by the transplant community over the last 50
  years
• Donors and recipients will be exploited by
  unscrupulous middlemen

52
Objections to Paid Donation

• Poor people sell kidneys because of financial
  desperation. This constitutes coercion
• People selling kidneys may be uneducated and
  unable to understand the risks of donation

53
Objections to Paid Donation

• Only the rich will be able to buy kidneys
• Paid donation will result in the disappearance of
  altruistic donation

54
How Much Does a Kidney Cost?

• E-Bay, 1999 5.7 Million
• Bolivia 2006 40,000
• Iran 1988-present 1200 health insurance
  recipient gift
• Pakistan, 2000 11,000
• Iraq, 1987 800-2000 to donor 20,000
  total cost to recipient
• Guest Hospital Chenai,1990 1000 , 3 yrs of
  medical Care
• England, 1989 6000
• India Black Market, 1984-88 2800-3300
• Vermont, 1984 100 and a set of tires

55
Kidney Purchase PackageIsrael 1997

• 145,000 includes
• 10,000 to donor (promised 30,000)
• Chartered round trip flight to Turkey
• Transport for Israeli transplant surgeon and
  nurse
• Transport to hospital (cab driven by former
  vendor who bought the cab with his payment
• Brokers fee (?10)
• Surgeons fees for Turkish and Israeli teams
• 25 of post transplant patients followed at
  Hadassah University Hospital in Jerusalem
  purchased their kidneys
• New York Times Magazine 5-27-01

56
Government Payment of DonorsThe Iranian
ExperienceN 19,609
Ghods and Savaj Clin J Am Soc Neph 1 1136-1145,
2006
57
Government Payment of DonorsThe Iranian
Experience

• Donor and Recipient Same Nationality
• Aged 20 to 35
• Good Health
• Written Consent of Spouse or Parent

Griffin, A. BMJ 334502-505
58
What the Donor Receives

• 1200 from the government
• One year of free health care
• Negotiated additional gift from recipient
• Griffin, A. BMJ 334502-505

59
Educational Level Iranian Paid Donors and
Recipients
60
Vendor Perception in Iran after NephrectomyN300

• Would not sell kidney again 85
• Would strongly discourage others 75
• Markedly negative effect on employment 60
• Major factor in divorce 21
• No follow-up visits after stitches out 79
• Markedly negative effect on physical
  abilities 60
• Kidney vending is a form of prostitution 73
• Not willing to inform anyone of vending 94
• Zargooshi. Journal of Urology Vol 166, 1790-1799,
  2001

61
Black Market Vendors in PakistanN239

• Average debt 1311
• Sale Price 1737
• Donor share 1377
• Bonded laborers 69
• Illiterate 90
• No economic gain 88
• Deterioration in health 98
• Naqvi A Transplant International. 2007

62
Downside to Black Market Kidney Sales for
RecipientsPoor Quality ControlN130

• 6.2 Immediate Surgical Morality
• 24 first year mortality rate
• 4 patients acquired HIV
• 2 patients acquired TB. 1 Fatal
• 5 Hepatitis B
• Salahudeen et al. Lancet 336725-728, 1990

63
Guidelines for Rewarded Donation

• Paid for and Regulated by an Impartial
  Organization (government or charity)
• No recipient donor contact or payment
• Reward should be non monetary, something money
  cant buy (at least not the money the donor has)
• Reward should be life changing
• Donor should be guarantied health care
• (as should everyone)

64
Proposed Rewards for Living Donors

• Pay off Medical School Debts
• Convert J -1 Visa to a Green Card
• Convert ARM to a low fixed rate mortgage
• Parking Space in Manhattan
• A pair of dress shoes that look nice and are
  comfortable
• Tickets to Cubs World Series Victory Game

65
Paired Donation

• ABO incompatible for A and B donor recipient
  pairs
• Positive crossmatch
• Donor gives to someone on the waiting list and
  her intended recipient gets the next suitable
  kidney

66
Countries which have used Organs from Executed
Prisoners

• China
• Taiwan
• Singapore
• France
• United States

67

• Deceased Donors

68
Proposals to Increase Deceased Donors

• Change in Kidney allocation
• Extended criteria donors
• Donors with high risk life style
• Non heart beating donors
• Mandated Choice
• Presumed Consent
• Conscription of kidneys
• Paying donor families
• Xenograft
• Growing Kidneys from Embryonic Cells

69
Proposed Changes in Organ AllocationNet Benefit

• Kidneys would preferentially be given to younger
  patients
• Decrease the importance of waiting time
• Preference for young diabetics
• Abandon preference for perfect matches

70
Age Distribution of Recipients Current vs
Proposed
71
Deceased Donor TransplantsYoung vs Old of
deceased donor kidneys
72
Downside of New Guidelines

• When children were given preference, living
  donors for children decreased
• Age is only one predictor of poor graft survival
• Takes away hope and sense of fairness

73
Living Donors vs Deceased Donors for Children 18 LD vs DD
74
Number of Transplants in Children 75
Transplants Age 18-34
76
Survival Benefit of Transplant from Extended
Criteria Donor

• 5 yr Graft Survival 5 yr PatientSurvival
• Waiting List N/A 61.2
• N80,283
• Marginal Donor 53 74
• Transplant
• N7540
• Ideal Donor 67 80
• Transplant
• N34,351
• Ojo et al. J Am Soc Nephrol 12589-597,2001

77
Classification of Donors after Cardiac
DeathMaastricht Classification

• Type 1 Death Outside the Hospital
• Type 2 Unsuccessful Resuscitation in ER
• Type 3 Imminent Cardiac Arrest following
  Withdrawal of Life Support
• Type 4 Cardiac Arrest After Brain Death
• Type 5 Unsuccessful Resuscitation Unexpected
  ICU Cardiac Arrest

78
Donation After Cardiac Death

• In the USA, almost all are type 3
• Cardiac Arrest after Withdrawal of Life Support
• Life support is withdrawn either in the ICU or
  OR. Organs are removed between 2 and 5 minutes
  after cessation of heart function

79
Transplants from Non Heart Beating Donors

• Kidney Type Brain Dead NHBD
• N8718 N 229
• Required Dialysis 21 48
• 1 yr graft Survival 86 83
• Trauma 89
• Other 78
• 1 yr creatinine 1.8 1.9
• Cho et al. N Eng J Med338 221-225, 1998

80
Donors with Out of Hospital Cardiac Arrest (Spain)

• Transported to ER with CPR and Ventilation en
  route
• Put on cardiac by-pass in the ER
• Maximum Warm Ischemia Time 120 minutes
• Maximum bypass time 240 minutes
• Age
• Sanchez-Fructuoso et al Ann Int Med145 157-164,
  2006

81
Donors with Out of Hospital Cardiac Arrest

• Graft Survival 1 yr 5 yrs
• Brain Dead Donors
• N 458
• Brain Dead Donors 60 yrs 79.8 73.3
• N 126
• Non Heart Beating 87.4 82.1
• 79.8 DOA
• N 320
• Sanchez-Fructuoso et al Ann Int Med145 157-164,
  2006

82
Likely Approaches

• Increased altruistic donation
• Non monetary rewards
• Internet donor recipient contact
• Paired Exchange
• Non heart beating Donors
• Compensation for donor families

83

• Thank You

84

• ????

85
Transplants 65
86
Economic Status of Iranian Paid Donots and
Recipients
87
Waiting List by Age
88
Waiting and Transplant by Ethnic Group
89
More exclusions

• Remote History of breast cancer, melanoma,
  lymphoma, choriocarcinoma, kidney, colon
• High grade brain tumors
• Brain tumors with ventriculoperitoneal shunts

90
Transplant Recipients over 65
91
Exclusions

• Active malignancy except primary brain tumor,
  squamous and basal cell skin cancer
• Lymphoma/Leukemia
• Viral infections HIV, measles, rabies, herpes
  menigoencephlatis, prion related disease

92
High Risk Transplant Recipients

• Age over 70 yrs
• Heart Disease
• Diabetes
• Hepatitis C
• HIV positive patients

93
Age of Renal Transplant Recipients
94
Dialysis Patient Survival Diabetes vs HIV
95
Hypertension and Creatinine 1.5 mg/dl

• Donor Characteristic Relative Risk
• Age 60 HBP 2.16
• Age60 HBP ? Cr 2.36
• Age 50-59HBPCVA 1.83
• Age 50-59HBPCVA? CR 1.99
• Age 60HBPCVA 2.47
• Age60HBPCVA ? CR 2.69
• Port et al, Transplantation, 2002

96
Unusual Cadaveric Donors

• Horseshoe Kidney
• Encephalitis
• Poisoned Patients
• Kidneys from recipients of other donated organs

97
Expanded Criteria Deceased Donors

• Donors with abnormal renal function
• Donors over age 60
• Donors with diabetes and normal renal function
• Donors with hypertension
• Donors with bacteremia or urine culture without
  pyelonephritis

98
Deceased Donor Causes of Death
99
Age of Deceased Donors
100
Biopsy of Kidneys from Donors 60 yrs

• Donors 60 No
  BX Donors60
• kidneys 124 116 124
• recipients 124 62 124
• graft survival 88.7 90.3 68.5
• Patient survival 95.2 96 92
• Remuzzi et al New Eng J Med 354343-352, 2006

101
Relative Risk vs 3 yr Graft Survival

• Relative Risk 3 Yr Graft Survival
• 1.7-2.0 71.7
• 2.0-2.5 65.6
• 2.5 49.4
• All 1.7 68
• Port et al., Transplantation, 2002

102
Pennsylvania Law 105

• 10 of the total fund (The Organ Donor Awareness
  Trust Fund) may be expended annually by the
  Department of Health for reasonable hospital and
  other incidental expenses incurred by the donor
  or the donors family in connection with making a
  vital organ donation.
• Such expenditures shall not exceed 3000 per
  donor and shall be paid directly to the funeral
  home, hospital or other service provider.

103
Illinois, 2005

• If the deceased has signed a donor card, the
  family cannot refuse donation.
• Approximately 30 such donors per year were lost
  prior to the law.
• May allow donation when there is a delay in
  reaching the family

104
How do we allocate kidneys from altruistic donors?

• Donor preferences
• Time on the waiting list
• Exclusions
• Cost prohibitive to crossmatch every altruistic
  donor with all sensitized patients
• Short life expectancy because of comorbidities
• High chance of transplant failure previous
  recurrent focal sclerosis or non compliance.
• Extreme size or age mismatch

105
Age of Living DonorsDonors aged 50-64
106
Altruistic Kidney Donor

• Should the donor decide who receives the kidney?
• The living donor kidney is a gift
• Donation involves emotional connection to the
  idea of recipient
• More donors will donate if they have a say.

107
Altruistic Kidney Donors

• Should the donor decide?
• Against
• Might make donation on the basis of unacceptable
  prejudices.
• Public resources and participation of health care
  workers are needed to carry out the transplant.
  They should have a say.
• Only 21 of people surveyed said they would not
  donate if their donation was undirected

108
Downside to Black Market Paid DonationDonors

• Amount of payment solves short term problems only
• Minimal Long term medical follow-up
• Donors report long term health and financial
  problems

109
Downside to Non Paid Living Donation

• Not enough donors
• Coercion exists with altruistic donation,
  especially within families.
• No long term follow up on donors with medical
  problems
• Donors may not report contraindications to
  donation, especially those potentially harmful to
  themselves

110
Survey of Attitudes toward Directed Altruistic
Donation1028 respondents

• Should altruistic donors be allowed to select a
  specific type of recipient?
• Yes 21
• Probably yes 15
• No 52
• Probably no 10
• Dont know 2
• Spital,A Transplantation vol 761252-1256, 2005

111
Transplants from Non Heart Beating Donors USA