Racial disparaties in Chronic Kidney Diseases

2,392 views

Published on

Published in: Education
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
2,392
On SlideShare
0
From Embeds
0
Number of Embeds
572
Actions
Shares
0
Downloads
28
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Racial disparaties in Chronic Kidney Diseases

  1. 1. Racial Disparities in CKD/ESRD Kellie Calderon, MD Hofstra North Shore-LIJ Nephrology, USA
  2. 2. Racial Disparity in CKD/ESRD <ul><li>“ It is much more important to know what sort of a patient has a disease, than what sort of disease a patient has.” </li></ul>William Osler (1849-1919)
  3. 3. Racial Disparity in ESRD 4.8 3.8
  4. 4. 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
  5. 5. 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).
  6. 6. Cumulative Incidence of CKD by age and race AA White
  7. 7. 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.
  8. 8. 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
  9. 9. Racial Differences in Risk of End-Stage Renal Disease and Death <ul><li>National Sample: </li></ul><ul><ul><li>2,015,891 veterans </li></ul></ul><ul><ul><li>2001-2005 </li></ul></ul><ul><li>Objective: </li></ul><ul><ul><li>Compare white/black differences in ESRD and Death to identify at what level of kidney function the racial disparities are the greatest </li></ul></ul>
  10. 10. Racial Differences in Risk of End-Stage Renal Disease and Death <ul><li>Study Sample: </li></ul><ul><ul><li>All veterans with outpatient creatinine measured </li></ul></ul><ul><ul><li>Excluded: </li></ul></ul><ul><ul><ul><li>ESRD </li></ul></ul></ul><ul><ul><ul><li>Transplant </li></ul></ul></ul><ul><ul><li>Follow ups link by USRDS </li></ul></ul>
  11. 14. Age-standardized incidence of death by estimated glomerular filtration rate (GFR) at baseline White/Black Racial Differences in Risk of End-Stage Renal Disease and Death Andy I. Choi et al. American Journal of Medicine, 2009 Do differences in mortality rate account for these differences??
  12. 15. Results: <ul><li>Rates of ESRD exceeded those among white patients </li></ul><ul><ul><li>ALL levels of baseline GFR </li></ul></ul><ul><li>Similar pattern for mortality </li></ul><ul><ul><li>Equal or higher rates of death among black persons </li></ul></ul><ul><ul><li>Highest risk of mortality in blacks with eGFR 45-59cc/min </li></ul></ul>
  13. 16. Hsu, C.-y. et al. J Am Soc Nephrol 2003;14:2902-2907 Relative risks for progression from CKD to ESRD cases overall and by subgroup
  14. 17. Journal of the National Medical Association Aug 2002
  15. 18. Previously Described Factors: <ul><li>Environmental </li></ul><ul><ul><li>Access to Health care </li></ul></ul><ul><ul><li>Economic status </li></ul></ul><ul><ul><li>Low Birth Weight </li></ul></ul><ul><ul><li>Higher incidence of co-morbidities </li></ul></ul><ul><ul><ul><li>DM </li></ul></ul></ul><ul><ul><ul><li>HTN </li></ul></ul></ul>
  16. 19. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke <ul><li>Purpose: </li></ul><ul><ul><li>Identify factors that contribute to the excess stroke mortality among black individuals and in the southeastern US </li></ul></ul>
  17. 20. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke <ul><li>Population based Cohort study </li></ul><ul><li>American 45+ years </li></ul><ul><ul><li>½ black, ½ male </li></ul></ul><ul><li>Targeted Sample size of 30,000 persons </li></ul>
  18. 21. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke <ul><li>Patient population: </li></ul>20% 30% 50%
  19. 22. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke
  20. 23. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke <ul><li>Stroke Risk: </li></ul><ul><ul><li>Blacks in “stroke belt” were more likely to: </li></ul></ul><ul><ul><ul><li>Be aware of HTN </li></ul></ul></ul><ul><ul><ul><li>Be on treatment for HTN </li></ul></ul></ul>
  21. 24. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke eGFR<60cc/min 43.3% Blacks: 33.7% Whites: 49.9% N = 20,669
  22. 25. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke Average GFR: Blacks: 65.9 White: 60.1
  23. 26. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke GFR 10-20cc/min: Black: 0.7% White: 0.2%
  24. 27. <ul><li>Conclusions: </li></ul><ul><ul><li>Disparity in ESRD incidence in US black and white individuals MAY to due to differences in: </li></ul></ul><ul><ul><ul><li>The Rate of Progression of CKD </li></ul></ul></ul><ul><ul><ul><li>Overall survival with advanced stages of CKD </li></ul></ul></ul>
  25. 28. REGARDS Study: Reasons for Geographic And Racial Differences in Stroke
  26. 29. <ul><li>Kidney Function, Albuminuria, and All-Cause Mortality in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study </li></ul>
  27. 30. Maybe “environmental”…
  28. 31. Genetic Analysis Nature Genetics 40 , 1175 - 1184 (2008) Published online: 14 September 2008 | doi:10.1038/ng.226 Jeffrey B Kopp 1 , 17 , Michael W Smith 2 , 16 , 17 , George W Nelson 2 , 17 , Randall C Johnson 2 , Barry I Freedman 3 , Donald W Bowden 3 , Taras Oleksyk 2 , Louise M McKenzie 2 , Hiroshi Kajiyama 1 , Tejinder S Ahuja 4 , Jeffrey S Berns 5 , William Briggs 6 , Monique E Cho 1 , Richard A Dart 7 , Paul L Kimmel 8 , Stephen M Korbet 9 , Donna M Michel 10 , Michele H Mokrzycki 11 , Jeffrey R Schelling 12 , Eric Simon 13 , Howard Trachtman 14 , David Vlahov 15 & Cheryl A Winkler 2 MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis
  29. 32. <ul><li>MALD </li></ul><ul><ul><li>Mapping Admixture Linkage Disequilibrium </li></ul></ul><ul><ul><li>Strategy for identifying genes underlying ancestry-driven health disparities </li></ul></ul>
  30. 35. <ul><li>Nonmuscle myosin heavy chain 9 </li></ul>
  31. 36. MYH9 Chromosome 22q12 1960 Amino Acids 227kDa Expressed in: Platelets Thymus Spleen Kidney
  32. 37. MYH9 <ul><li>Function: </li></ul><ul><ul><li>Binds actin </li></ul></ul><ul><ul><li>Protein of the cytoskeleton </li></ul></ul><ul><ul><li>Role in cell shape and motility </li></ul></ul><ul><ul><li>Role in cell division </li></ul></ul>
  33. 38. MYH9 <ul><li>AD Giant Platelet Disorders </li></ul><ul><ul><li>Triad: </li></ul></ul><ul><ul><ul><li>Thrombocytopenia </li></ul></ul></ul><ul><ul><ul><li>Large Platelets </li></ul></ul></ul><ul><ul><ul><li>Leukocyte Inclusions </li></ul></ul></ul>
  34. 39. MYH9 <ul><li>2000: Described in a set of overlapping syndromes: </li></ul><ul><ul><li>macrothrombocytopenia, </li></ul></ul><ul><ul><li>Inclusion bodies in neutrophils </li></ul></ul><ul><ul><li>sensorineural deafness </li></ul></ul><ul><ul><li>cataracts </li></ul></ul><ul><ul><li>glomerular injury </li></ul></ul><ul><li>Linked to MYH9 coding region mutations </li></ul><ul><ul><li>Missense </li></ul></ul><ul><ul><li>nonsense </li></ul></ul><ul><ul><li>deletions </li></ul></ul>
  35. 40. Mutations in MYH9: The May-Hegglin Anomaly Fechtner Syndrome Sebastian syndromes Sensorineural Hearing Loss Cataracts Nephritis
  36. 41. <ul><li>In the kidney… </li></ul><ul><ul><li>Encodes for Podocyte nonmuscle myosin IIa </li></ul></ul>
  37. 42. 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
  38. 43. 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
  39. 44. AASK Re-visited… <ul><li>Tested for 4 polymorphisms in MYH9 </li></ul><ul><ul><li>497 Participants with Hypertensive nephropathy </li></ul></ul><ul><ul><li>946 AA Controls from </li></ul></ul>Preliminary analysis indicates that tendency to lose kidney function over time Is associated with MYH9 variants!! Wake Forest
  40. 45. A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9 2010 International Society of Nephrology
  41. 46. <ul><li>Found that APOL1 variants associated with non-diabetic glomerular disease in AA populations </li></ul><ul><ul><li>Stronger association than with European Americans </li></ul></ul><ul><ul><li>Higher prevalence of this gene than anticipated in population </li></ul></ul><ul><ul><ul><li>Suggests a recent natural selection </li></ul></ul></ul>
  42. 47. Apolipoprotein L1 <ul><li>Located on Chromosome 22q12 </li></ul><ul><li>Protein component in HDL </li></ul>
  43. 48. Apolipoprotein L1 <ul><li>Innate Immunity </li></ul><ul><ul><li>Trypanosomas brucei brucei </li></ul></ul><ul><ul><ul><li>Trypanosoma brucei rhodesiense Resistant </li></ul></ul></ul><ul><ul><ul><li>Trypanosoma brucei gambiense Resistant </li></ul></ul></ul><ul><ul><li>HDL particles taken up by the parasite </li></ul></ul><ul><ul><li>Generates ionic pores in the lysosomal membrane </li></ul></ul>
  44. 49. The trypanolytic factor of human serum Etienne Pays, Benoit Vanhollebeke, Luc Vanhamme, Françoise Paturiaux-Hanocq, Derek P. Nolan and David Pérez-Morga Nature, 2006 Human Sera Recombinant ApoL1
  45. 50. <ul><li>Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans </li></ul><ul><li>Giulio Genovese et al. </li></ul><ul><li>Originally published in Science Express on 15 July 2010 Science 13 August 2010: Vol. 329. no. 5993, pp. 841 - 845 </li></ul>
  46. 51. 205 AA “idiopathic” FSGS 180 AA Controls Strongest genetic association found was APOL1 Two Locus allele “G1” FSGS 52% Controls 18%
  47. 52. 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
  48. 53. L. Lecordier et al. PLoS Pathogens 2009 C-terminal mutants of apolipoprotein L-I efficiently kill both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense
  49. 54. Trypanosoma brucei rhodesiense African Sleeping Sickness. Serum Resistance Associated Protein C Terminal Helix of APOL1 Resistant to ApoL1 destruction G1 and G2 located there!!
  50. 55. Nephron Power, 2010 <ul><li>IN THE NEWS- </li></ul><ul><li>&quot; Its not me, its the guy next to me,&quot; </li></ul><ul><li>says MYH9 </li></ul>

×