Transcript Black, Hispanic and White Living Kidney Donors

PROTECTING OUR HEROES:
BLACK, HISPANIC AND WHITE
LIVING KIDNEY DONORS- WHO
IS AT RISK AND WHY?
Horacio E. Adrogue, MD, FASN
Associate Prof. of Medicine Division of
Nephrology UT health
Medical Director of Kidney and Pancreas
Transplantation
Memorial Herman Hospital Texas Medical
Center
AMAT 2014
 Understand
the scope of the
problem of kidney disease
 Understand
the donor perspective
of live kidney donation
 Understand
the risks specific to
different donor race and gender
LEARNING OBJECTIVES
 The
2013 USRDS report showed that by
the end of 2011 over 430,000 patients
were on dialysis and another 185,000
were alive with a functioning kidney
transplant.
 An
estimated 20 million people have
some form of CKD
 128,000
people started dialysis in 2011
 2,800
people received a preemptive
kidney transplant in 2011.
SCOPE OF THE PROBLEM
 As
the current UNOS kidney transplant
waiting list now exceeds 100,000 people
it is more important than ever to ensure
that in selecting live donors we do not
inadvertently contribute to future
chronic kidney disease.
 In the spirit of transparency and informed
consent transplant programs
continuously struggle with giving
potential donors the most up-to-date
and detailed information that is
available about their personal risk for
chronic kidney disease associated with
the donation event.
SCOPE OF THE PROBLEM

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
In the United States, approximate 6000 healthy
adults choose to donate a kidney to family
member, friend or stranger every year. Studies
have shown that18% of live donors do not have
health insurance at the time of donation.
Many studies have been done comparing these
donors to the general unscreened population.
Studies to date have shown that the general
unscreened population appears to have a
higher risk of end-stage kidney disease than
carefully screened donors.
The following study compared live donors to
matched carefully screened non-donors and the
general unscreened non-donor population.
SCOPE OF THE PROBLEM
 30
year old Black female with no
significant past medical or surgical
history not taking any medications.
 No family history of hypertension, endstage kidney disease.
 Estimated GFR is 100 mls per minute,
urine microalbumin is less than 30 and
urinary albumin to creatinine ratio is 0.01
 2 hour oral glucose tolerance test is
normal, 24 hour ambulatory blood
pressure is normal.
DONOR 1
 30
year old White female with no
significant past medical or surgical
history not taking any medications.
 No family history of hypertension, endstage kidney disease.
 Estimated GFR is 100 mls per minute,
urine microalbumin is less than 30 and
urinary albumin to creatinine ratio is 0.01
 2 hour oral glucose tolerance test is
normal, 24 hour ambulatory blood
pressure is normal.
DONOR 2
 30
year old Hispanic female with no
significant past medical or surgical
history not taking any medications.
 No family history of hypertension, endstage kidney disease.
 Estimated GFR is 100 mls per minute,
urine microalbumin is less than 30 and
urinary albumin to creatinine ratio is 0.01
 2 hour oral glucose tolerance test is
normal, 24 hour ambulatory blood
pressure is normal.
DONOR 3
 All
adult live donors in the United States
between April 1, 1994 and November 30,
2011 were included in this study
(n=96,217).
 ESRD outcomes were ascertained by
linkage to the CMS 2728 form and the
transplant network kidney waiting list
databases.
 The matched known donor population
was drawn from the NHANES III data set
between 1988 and 1994
 Matching was based on age, sex, self
identified race, educational
background, BMI, smoking history, and
systolic blood pressure.
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 78%
of the donors were younger than
50 years
 59% were women
 75% were white
 64% had attended college at some
point
 68% of donors were biologically
related to the recipient
 25% considered obese ( BMI greater
than 30)
 9% had a systolic blood pressure
greater than 140 mmHg
 24% smoke cigarettes at the time of
donation
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 Among
20,024 unscreened adults who
participated in NHANES III, 9364 (47%)
had no identified contraindications to
kidney donation after screening and
were matched one-to-one to donors to
create a healthy non-donor cohort of
96,217 patients to compare with the
96,217 live donors.
 Some
authors have noted that using
the same patients as multiple controls
may lead to an underestimation of
end-stage kidney disease.
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 It
is important to note that in the NHANES
III group a history of asthma, any cancer
besides skin cancer, hypertension and
kidney stones were all considered
contraindications for kidney donation.
 In
most transplant centers history of
asthma and a history of past kidney
stones would not necessarily be
considered a contraindication for
donation. This fact may have
contributed to an underestimation of risk
of end-stage kidney disease in this
population non-donor population.
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 With
a median follow-up of 7.6 years,
end-stage kidney disease developed in
99 live donors
 83 of 99 who developed end-stage
kidney disease were biologically related
to the recipient.
 By contrast among matched healthy
non-donors with a median follow-up of
15 years, end-stage kidney disease
developed in 17 individuals among the
9364 participants.
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 The
absolute risk of end-stage kidney
disease was highest among black
donors at 74 per 10,000 versus 24 per
10,000 black non-donors.
 Risk
among Hispanic donors was 32 per
10,004 Hispanic non-donors 6.7 per
10,000
 Absolute
risk was lowest in White donors
at 23 per 10,000 and white non-donors at
0 per 10,000
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 96
per 10,000 black men versus 34 per
10,000 white men had end-stage kidney
disease at 15 years
 58
per 10,000 black women versus 15
per 10,000 white women experienced
end-stage kidney disease at 15 years
 The
authors concluded that live donors
had a lower estimated lifetime risk than
the general population by age 80 at 90
per 10,000 in the donors versus 326 per
10,000 in the unscreened general
population.
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 Although
this study may have had some
shortcomings, it is likely fair to say that
the risk of end-stage kidney disease of
the living donor is less than the general
unscreened population but more than
matched controls.
 It
is reasonable to consent African
Americans and Hispanics as having a
higher risk of end-stage kidney disease
after donation when compared to
Whites.
RISK OF ESRD FOLLOWING LIVE KIDNEY DONATION
MUZAALE AD ET AL, JAMA 2/12/2014
 Donor
1 (Black female)-0.6% risk of ESRD
at 15 years (0.96% if male)
 Donor
2 (White female)-0.14% risk for
ESRD at 15 years (0.34% if male)
 Donor
3 (Hispanic female)-0.33% risk for
ESRD at 15 years
WHAT DO I TELL THE DONORS?
 Studies
have shows that specific “risk”
variants of the APOL1 gene located on
chromosome 22 are strongly associated
with ESRD in African Americans.
 Carriers
of 2 such alleles (10-12% of the
general AA population) have an OR of
10.5 for ESRD due to FSGS and 7.3 for
ESRD due to hypertension. The risk of HIV
nephropathy is also elevated. This is still
an association not proven to be a
cause.
 The
rate of ESRD due to hypertension in
AA between 30-39 years is more than 10
times higher than their European
counterparts.
AFRICAN AMERICAN LIVING-KIDNEY DONORS
SHOULD BE SCREENED FOR APOL1 RISK ALLELES
COHEN DM ET AL, TRANSPLANTATION VOL 92, NU 7,
OCT 2011

APOL1 is a soluble protein found in plasma
bound to high-density lipoproteins.

It has been found localized to podocytes and
proximal tubular epithelial cells in the kidney.

In people of African descent the trypanolytic role
of APLO1 in defending against African Sleeping
Sickness is via the circulating serum protein.
AFRICAN AMERICAN LIVING-KIDNEY DONORS
SHOULD BE SCREENED FOR APOL1 RISK ALLELES
COHEN DM ET AL, TRANSPLANTATION VOL 92, NU 7,
OCT 2011

In a study of 136 recipients of kidneys from AA
deceased donors the incidence of graft loss at 2
years was more than double with 2 APOL1 risk
alleles.

Are these allografts genetically pre-programmed
for premature failure after transplantation?

Another study of 58 AA recipients who
themselves had 2 APOL1 risk genes did not show
worse 5 year allograft survival.

The difference between the study groups is that
the deceased donor kidney with the defect did
not appear to last as long in a recipient. The
second study followed those whose native
kidneys had already failed and who received an
allograft with an unknown genetic risk profile.
THE APOL1 GENE AND ALLOGRAFT SURVIVAL AFTER KIDNEY TRANSPLANT.
REEVES-DANIEL AM ET AL. AJT 11(5):1025-1030 2011
THE APOL1 GENOTYPE OF AA KIDNEY TRANSPLANT RECIPIENTS DOES NOT
IMPACT 5-YEAR ALLOGRAFT SURVIVAL. LEE BT ET AL. AJT 12: 1924-1928 2012
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A 22 yo man of Afro-Caribbean origin with
unknown cause of ESRD (no biopsy) received a
living donor kidney transplant from his identical
twin in Henri Mondor, France (2006).
Pt only got 2 iv doses of methylprednisolone and
2 weeks of po prednisone. His creatinine was 1.2
mg/dl at day 10.
At 6 months he has 1.2 grams proteinuria with 3
drug hypertension and a normal allograft biopsy.
Thirty months after transplant he presents with a
creatinine of 2.6 mg/dl and 2.2 grams
proteinuria. A biopsy showed FSGS, IFTA and no
C4D. Dialysis was planned at 5 years post
transplant.
Seven years after donation the brother (donor)
had a creatinine of 2.5 mg/dl and 2.5 grams
proteinuria. No kidney biopsy was done but both
were positive for the APOL1 gene.
APOL1 POLYMORPHISMS AND DEVELOPMENT OF
CKD IN AN IDENTICAL TWIN DONOR AND RECIPIENT
PAIR. KOFMAN T ET AL. AJKD 63(5):815-819. 2014

1589 female donors from the University of Minnesota
responded to a post-donation pregnancy survey.

Fetal and maternal outcomes were compared to
the general non-donor population

Post (vs. pre)donation pregnancies were
associated with a lower likelihood of full-term
deliveries (73.7% vs. 84.6% p=0.0004) and higher
likelihood of fetal loss (19.2% vs. 11.3% p<0.0001).

Post-donation pregnancies were associated with a
higher risk of gestational diabetes (2.57% vs. 0.7%);
gestational hypertension (5.7% vs. 0.6%); proteinuria
(4.3% vs. 1.1%) and preeclampsia (5.5% vs. 0.8%).
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All p values were less than 0.005.
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The authors conclusion was that pregnancy
outcomes were similar to those reported in the
general non-donor population but inferior to the
pre-donation pregnancy outcomes in the same
donor.
PREGNANCY OUTCOMES AFTER KIDNEY
TRANSPLANT IBRAHIM HN ET AL. AJT APRIL ;
9(4):825-834 2009
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CKD is very common in the USA and the world

Live kidney donors are a healthy, altruistic group
who deserve very careful evaluation and honest full
disclosure of known and unknown risk of
nephrectomy.

Blacks, women and Hispanics appear to have
increased risk of CKD and other issues after
donation

We owe it to our heroes to continue to better risk
stratify them as they put their lives in our hands.

I think all AA donors should be screened for the
APOL1 genetic polymorphisms.
SUMMARY