9/30/2016 Pre-Test (True/False) There is an abundance of living - - PowerPoint PPT Presentation

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9/30/2016 Pre-Test (True/False) There is an abundance of living - - PowerPoint PPT Presentation

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9/30/2016 Pre-Test (True/False) There is an abundance of living organ donors in the community Living Kidney Donors Living kidney donors are no more likely to The Unspoken Risks develop End Stage Renal Disease than non- donors The

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9/30/2016 1 Living Kidney Donors The Unspoken Risks Transplant Symposium 2016

Brian K Lee, M.D.

May 14th 2014

Connie Frank Transplant Center

School of Medicine

Pre-Test (True/False)

  • There is an abundance of living organ donors in

the community

  • Living kidney donors are no more likely to

develop End Stage Renal Disease than non- donors

  • The emergence of Chronic Kidney Disease

among donors happen soon after surgery

  • Risks to kidney donors far outweighs the

benefits to their recipients

2 School of Medicine

Donation Trends

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OPTN/SRTR Annual Data Report 2012

School of Medicine

Allograft Survival

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OPTN/SRTR Annual Data Report 2012

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9/30/2016 2

School of Medicine

Once Apron A Time…..

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Health of Donor….

  • “ The health of the donor dominates all other
  • considerations. A major operation on a normal

person, not for his own benefit, requires a brusque re-evaluation of traditional surgical thought….moral justification is found in the safety and security of the donor as well as in the expected degree of success when there is no

  • ther alternative.”

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Murray et al. Ann Surg 1958; 148:343-59

School of Medicine

Uninephrectomy in Childhood

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  • 111/224 eligible candidates

evaluated

  • FU range 7-52 yrs
  • Inulin and PAH clearances done
  • Solitary kidney regained 75-80%

GFR expected of two kidneys

  • ERPF was ↑30% in single kidney
  • 23% had microalbuminuria, of whom

6 had excretion ≥ 250mg/day

Baudoin et al. AJKD 1993; 21:603-11

School of Medicine

Donor Survival

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The State of Affairs Pre-2013

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9/30/2016 3

School of Medicine

Donor vs. Gen Pop Survival Data

Country Origin Setting N= Years studied FU (yrs) Sweden Single center 430 1964-1994 1-35 Japan Single center 481 1970-2006 1-35 France Single center 310 1952-2008 1-53 USA Single center 3698 1963-2007 1-45

9 School of Medicine 10

Sweden Japan France USA

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  • 80K + live kidney donors in US, 1994-2009
  • Comparison group – selected cohort from NHANES III ‘88-’94
  • Median FU period 6.3 yrs

Segev et al. JAMA 2010; 303:959-66

Donor vs. Selected “Healthy” Population

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Garg et al. BMJ 2012; 344:e1023

Donor vs. Selected “Healthy” Population

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School of Medicine

Kidney Dysfunction

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The State of Affairs Pre-2013

School of Medicine

ESRD in Donor Population

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  • 1112 consecutive donors in Sweden
  • Median time from donation to ESRD 20 yrs (14-27)
  • Of the 6 with ESRD, 4 reported from nephrosclerosis, only single

case was verified

  • Based on advanced age of donors at time of ESRD, rates were

comparable to general population

Fehrman-Ekholm et al. Transplantation 1996; 82:1646-48

School of Medicine

Effect on GFR – Pooled Analysis

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Garg et al. KI 2006; 70:1801-10

School of Medicine

A Landmark Paper …..

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  • 3698 Kidney donors – ’63 through ‘07 @ U Minn
  • Cohort of 255 donors also had iohexol GFR and

albuminuria measured

  • Patient survival of donors compared to life

tables from Human Mortality Database

  • Rates of ESRD in general population estimated

to be 268 cases/million person-yrs (USRDS 2007 annual report)

  • NHANES 2003-4 and 2005-6 cohorts were

matched by age, sex, ethnicity, and BMI to donors in whom GFR was measured

Ibrahim et al. NEJM 2009; 360:459-69

School of Medicine 18

1 2 3 4

Causes of ESRD in Donors

ESRD Rate 180/ million person-yrs Female 7/11 Caucasian 8/11 Siblings 7/11 (all ESRD cases were LRRT)

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Limitations

  • 99% donors were Caucasian
  • Increasing acceptance of older donors, those

with HTN, obesity

  • Relied on patient contact/recall for diagnosis of

ESRD

  • Control group gleaned from general population,
  • vs. highly selected donor cohort

22 School of Medicine 23 School of Medicine 24

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Mjoen et al. KI 2014. 86:162-7.

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All Cause Mortality

School of Medicine 27

All-Cause and CV Mortality

School of Medicine

ESRD Risk in Donors

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  • Absolute risk of ESRD – 9/1901 donors = 0.47%
  • Median time to ESRD 18.7 yrs
  • 7/9 cases of ESRD was caused by immunologic disease –

hereditary component (most were close relatives)

  • Crude incidence - 302/million person-yrs amongst donors vs.

100/milion person-yrs in Norway population

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Limitations

  • 100% donors were Caucasian of Scandivian

ancestry

  • Most donors were relatives of recipients, not

necessarily generalizable to LURT / non- directed donations

  • Donors were selected from throughout Norway,

while controls belonged to single county exceptionally low mortality rates

  • Differing eras (donors 1963-2007) while controls

1984-87, with general mortality having improved between ‘63 and ’84

  • Longer FU amongst controls may have affected

mortality and ESRD rates

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  • 96,217 donors from 1994-2011
  • 2/3 of live donors were biologically related to recipient
  • Repeated matched done with 9364 non-donors, drawn from the

NHANES ‘88-’94 cohort, who had no contraindications to donation

  • ESRD defined as initiation of dialysis (CMS 2728), wait-listing for

kidney transplant, or receipt of Ktx

  • Baseline characteristics were similar, but noted 22% of donors

had eGFR < 80 cc/min

Muzaale et al. JAMA 2014; 311: 579-86

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Cumulative ESRD incidence

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Stratified by Ethnicity

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Absolute Risk Increases

Donor (per 10,000) Non-Donor (per 10,000) ∆AR (per 10,000) All 30.8 3.9 26.9 AA 74.7 23.9 50.8 Hispanics 32.6 6.7 25.9 Caucasian 22.7 22.7

School of Medicine

Life-time Risk of ESRD

School of Medicine

Limitations

  • Differing cohorts (donors 1994-2011, controls drawn

from ‘88-94) – recent increased ESRD incidence

  • Underestimation of ESRD risk in controls

a) Long event free survival repeatedly sampled b) Different competing risks of death

  • Increased surveillance for ESRD amongst donors
  • Prioritization of previous donors to the waitlist for

transplantation (so long as eGFR < 20cc/min)

  • Crude vs.15 yr cumulative incidence of ESRD

Incidence Donors (per 10,000) Non-Donors (per 10,000) Crude 10.3 18.2 15 yr cumulative 30.8 3.7

School of Medicine

Focus on Absolute Risks

% donors with ESRD Mjoen et al. 0.47% Muzaale et al. 0.1% Muzaale et al. 15 yr risk % Lifetime Risk % Donors 0.0031 0.009 Healthy Controls 0.0004 0.0014 General Pop N/A 0.033

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School of Medicine

The BottomLine …

  • Mjoen et al.

“Most potential living donors are willing to accept a degree of risk when the recipient is a family member or a close friend. Our findings will not change our opinion in promoting live-kidney donation.”

  • Muzaale et al.

“.. the magnitude of the absolute increase is small. These findings may help inform discussions with persons considering live kidney donation.”

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Informing Consent

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Framing Risk Discussion

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Turin et al. 2012; 23:1569-78

School of Medicine 40

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Framing Risk Discussion

Turin et al. 2012; 23:1569-78

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Counseling of Living Donors – Changing Paradigm ?

42

Steiner et al. AJT 2014; 14: 538-44

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Non-maleficence

Autonomy

School of Medicine

  • Primum non nocere
  • “ How do the risks and benefits of donation

compare to those of not donating? ”

  • Loss of a loved one
  • Care-giver burden
  • Disability, loss of household income,

childcare/family support (non-health benefits)

  • Labeling of potential donor as “unfit”

disappointment and guilt

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School of Medicine

OPTN Policy 12 – Living Donation

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Allen et al. AJT 2014; 14: 531-37

School of Medicine

Normal GFR vs Age and Gender

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Wetzels et al. KI 2007; 72: 632-37

School of Medicine

Summary

  • Donors have to accept that risks are ever-

changing as more information/data becomes available

  • Information/education presented in a

comprehensible manner is crucial in defining this risk

  • Absolute risk values may be more

representative

  • Caution towards close relatives of living donor

recipients (e.g. SLE, primary glomerular dz etc.)

  • Awareness on professionals part that there are

also “harms” to refusing a donor

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School of Medicine

Future Directives

  • Establishing prospective databases to assess

impact of reduced renal mass on mortality/GFR in the long term

  • Building a comparable cohort of “healthy” non-

donors (e.g. siblings of donors with similar health status)

  • Eliminating barriers to longitudinal donor

followup (advent of tele-medicine, reimbursing donors for local lab testing)

  • Identifying risk alleles in evaluation/selection of

potential donors (MYH9, APOL1 etc.)

49 School of Medicine

Post-Test (True/False)

  • There is an abundance of living organ donors in

the community

  • Living kidney donors are no more likely to

develop End Stage Renal Disease than non- donors

  • The emergence of Chronic Kidney Disease

among donors happen soon after surgery

  • Risks to kidney donors far outweighs the

benefits to their recipients

50 School of Medicine 51