Racial disparaties in Chronic Kidney Diseases
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Transcript of Racial disparaties in Chronic Kidney Diseases
Racial Disparities in CKD/ESRD
Kellie Calderon, MD
Hofstra North Shore-LIJ Nephrology, USA
Racial Disparity in CKD/ESRD
“It is much more important to know what sort of a patient has a disease, than what sort of disease a patient has.”
William Osler (1849-1919)
Racial Disparity in ESRD
ESRD Incidence by race
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1980 2002
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Series1
Series24.8
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Prevalent patients surviving cohort year, without CKD in prior year & without ESRD, age 65 & older (Medicare) & 20–64 (MarketScan & Ingenix i3).
Stages of incident CKD as defined by the new diagnosis codes:
Medicare patients age 65 & older, by race
2008
Data
Trends in CKD incidence: Medicare patients age 65 & older
Prevalent patients surviving cohort year, without CKD in prior year & without ESRD, age 65 & older (Medicare) & 20–64 (MarketScan & Ingenix i3).
Cumulative Incidence of CKD by age and race
AA
White
Median age of incident patients,
by race/ethnicity
Incident ESRD patients. For Hispanic patients we present data beginning in 1996, the first full year after the April 1995 introduction of the revised Medical Evidence form, which contains more specific questions on race & ethnicity.
Racial Differences in Risk of End-Stage Renal Disease and Death
Published American Journal of Medicine
July 2009
Andy I. Choi, et al.
VA Medical Center, San Francisco, CA
Racial Differences in Risk of End-Stage Renal Disease and Death
National Sample: 2,015,891 veterans 2001-2005
Objective: Compare white/black differences in
ESRD and Death to identify at what level of kidney function the racial disparities are the greatest
Racial Differences in Risk of End-Stage Renal Disease and Death
Study Sample: All veterans with outpatient creatinine
measured Excluded:
ESRD Transplant
Follow ups link by USRDS
Age-standardized incidence of death by estimated glomerular filtration rate (GFR) at baseline
White/Black Racial Differences in Risk of End-Stage RenalDisease and DeathAndy I. Choi et al. American Journal of Medicine, 2009
Do differences in mortality rate account for these
differences??
Results:
Rates of ESRD exceeded those among white patients ALL levels of baseline GFR
Similar pattern for mortality Equal or higher rates of death among
black persons Highest risk of mortality in blacks with
eGFR 45-59cc/min
Hsu, C.-y. et al. J Am Soc Nephrol 2003;14:2902-2907
Relative risks for progression from CKD to ESRD casesoverall and by subgroup
Journal of the National Medical AssociationAug 2002
Previously Described Factors:
Environmental Access to Health care Economic status Low Birth Weight Higher incidence of co-morbidities
DM HTN
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
Purpose: Identify factors that contribute to the
excess stroke mortality among black individuals and in the southeastern US
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
Population based Cohort study American 45+ years
½ black, ½ male Targeted Sample size of 30,000
persons
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
Patient population:
20%30%
50%
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
Stroke Risk: Blacks in “stroke belt” were more likely to:
Be aware of HTN Be on treatment for HTN
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
eGFR<60cc/min
43.3%
Blacks: 33.7%
Whites: 49.9%
N = 20,669
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
Average GFR:
Blacks: 65.9
White: 60.1
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
GFR 10-20cc/min:
Black: 0.7%
White: 0.2%
Conclusions: Disparity in ESRD incidence in US black
and white individuals MAY to due to differences in: The Rate of Progression of CKD Overall survival with advanced stages of CKD
REGARDS Study:Reasons for Geographic And Racial Differences in Stroke
Kidney Function, Albuminuria, and All-Cause Mortality in the REGARDS (Reasons for
Geographic and Racial Differences in Stroke) Study
Maybe “environmental”…
Genetic Analysis
Nature Genetics 40, 1175 - 1184 (2008) Published online: 14 September 2008 | doi:10.1038/ng.226
Jeffrey B Kopp1,17, Michael W Smith2,16,17, George W Nelson2,17, Randall C Johnson2, Barry I Freedman3, Donald W Bowden3, Taras
Oleksyk2, Louise M McKenzie2, Hiroshi Kajiyama1, Tejinder S Ahuja4, Jeffrey S Berns5, William Briggs6, Monique E Cho1, Richard A Dart7, Paul L Kimmel8, Stephen M Korbet9, Donna M Michel10, Michele H
Mokrzycki11, Jeffrey R Schelling12, Eric Simon13, Howard Trachtman14, David Vlahov15 & Cheryl A Winkler2
MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis
MALD Mapping Admixture Linkage
Disequilibrium Strategy for identifying genes underlying
ancestry-driven health disparities
Nonmuscle myosin heavy chain 9
MYH9
Chromosome 22q12
1960 Amino Acids
227kDa
Expressed in:
Platelets
Thymus
Spleen
Kidney
MYH9
Function: Binds actin Protein of the cytoskeleton Role in cell shape and motility Role in cell division
MYH9
AD Giant Platelet Disorders Triad:
Thrombocytopenia Large Platelets Leukocyte Inclusions
MYH9
2000: Described in a set of overlapping syndromes: macrothrombocytopenia, Inclusion bodies in neutrophils sensorineural deafness cataracts glomerular injury
Linked to MYH9 coding region mutations Missense nonsense deletions
The May-Hegglin AnomalyFechtner Syndrome Sebastian syndromes
Sensorineural Hearing Loss
Cataracts
Nephritis
Mutations in MYH9:
In the kidney… Encodes for Podocyte nonmuscle myosin
IIa
Copyright ©2010 American Society of Nephrology
Bostrom, M. A. et al. Clin J Am Soc Nephrol 2010;5:1107-1113
Figure 2. Proposed pathogenesis of MYH9-associated nephropathy
Re-visiting the AASK Cohort…
Association Analysis of the Non-Muscle Myosin Heavy Chain 9 Gene in
Hypertensive Nephropathy: Results from the African American Study of Kidney
Disease and Hypertension
AASK Re-visited… Tested for 4 polymorphisms in MYH9
497 Participants with Hypertensive nephropathy
946 AA Controls from
Preliminary analysis indicates that tendency to lose kidney function over time
Is associated with MYH9 variants!!
Wake Forest
A risk allele for focal segmental glomerulosclerosis in African Americans is
located within a region containing APOL1 and MYH9
2010 International Society of Nephrology
Found that APOL1 variants associated with non-diabetic glomerular disease in AA populations Stronger association than with European
Americans Higher prevalence of this gene than
anticipated in population Suggests a recent natural selection
Apolipoprotein L1
Located on Chromosome 22q12 Protein component in HDL
Apolipoprotein L1
Innate Immunity Trypanosomas brucei brucei
Trypanosoma brucei rhodesiense Resistant Trypanosoma brucei gambiense Resistant
HDL particles taken up by the parasite Generates ionic pores in the lysosomal
membrane
The trypanolytic factor of human serumEtienne Pays, Benoit Vanhollebeke, Luc Vanhamme,Françoise Paturiaux-Hanocq, Derek P. Nolan and David Pérez-MorgaNature, 2006
Human Sera
Recombinant ApoL1
Association of Trypanolytic ApoL1 Variants with Kidney Disease in
African Americans
Giulio Genovese et al. Originally published in Science Express on 15 July 2010
Science 13 August 2010:Vol. 329. no. 5993, pp. 841 - 845
205 AA “idiopathic” FSGS 180 AA Controls
Strongest genetic association found was APOL1
Two Locus allele “G1”
FSGS 52% Controls 18%
Larger Cohort:
Frequency of G1 and G2
Odds Ratio
1.26 for one-risk allele
7.3 for two-risk alleles
1030 AA H-ESRD
1025 AA matched controls
L. Lecordier et al.
PLoS Pathogens 2009
C-terminal mutants of apolipoprotein L-I efficiently kill both Trypanosoma brucei brucei and Trypanosoma brucei
rhodesiense
Trypanosoma brucei rhodesienseAfrican Sleeping Sickness.
Serum Resistance Associated Protein
C Terminal Helix of APOL1
Resistant to ApoL1 destruction
G1 and G2 located there!!
Nephron Power, 2010
IN THE NEWS-
" Its not me, its the guy next to me,"
says MYH9