Hemostatic factors, APOL1 risk variants, and the risk of ESRD in the atherosclerosis risk in communities study

Adrienne Tin, Morgan E. Grams, Nisa M. Maruthur, Brad C. Astor, David Couper, Thomas H. Mosley, Myriam Fornage, Rulan S. Parekh, Josef Coresh, Wen Hong Linda Kao

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background and objectives Hemostatic factors have been associated with kidney function decline, and evidence suggests stronger effects among African Americans. The presence of APOL1 renal risk variants, common in African Americans, might partly underlie this risk difference. Design, setting, participants, & measurements A total of 13,337 participants in the Atherosclerosis Risk in Communities study were followed from 1987–1989 until 2010. Participants were categorized into three groups by ancestry and APOL1 risk status: European Americans (n=10,206), African Americans with zero or one APOL1 risk allele (n=2,733), and African Americans with two APOL1 risk alleles (n=398). ESRD events were ascertained through linkage to the US Renal Data System. Cox regression was used to estimate the risk for ESRD associated with hemostatic factors (factor VIIc, factor VIIIc, fibrinogen, von Willebrand factor, protein C, and antithrombin III). Results Therewere 232 cases of ESRD over 21.5 years (European Americans, 119; African Americanswith zero or one APOL1 risk allele, 94; African Americans with two APOL1 risk alleles, 19). In unadjusted and adjusted analysis of the overall population, higher levels of all hemostatic factors, except antithrombin III, were significantly associated with ESRD (all P<0.05). Factor VIIc had the strongest association (per one interquartile range; adjusted hazard ratio, 1.46; 95% confidence interval, 1.21 to 1.76). With the exception of fibrinogen, the risk associatedwith each hemostatic factorwas stronger in African Americanswith two APOL1 risk alleles compared with the other two groups. Statistically significant interactions were seen for factor VIIIc and protein C (interaction between those with two APOL1 risk allele and the other two groups: P<0.02 for factor VIIIc and<0.04 for protein C). Conclusions Higher levels of factor VIIc, VIIIc, fibrinogen, vonWillebrand factor, and protein C were associated with ESRD risk, with a significantly stronger association of factor VIIIc and protein C in African Americans with two APOL1 risk alleles.

Original languageEnglish (US)
Pages (from-to)784-790
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number5
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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