title: Change in Multiple Filtration Markers and Subsequent Risk of Cardiovascular Disease and Mortality.
abstract: OBJECTIVE
  Kidney disease progression, assessed by change in eGFR on the basis of creatinine, is an independent risk factor for cardiovascular disease and death. This study aimed to evaluate whether changes in multiple filtration markers, individually and combined, were associated with cardiovascular disease and death.
  
  
  METHODS
  Creatinine, cystatin C, and β2-microglobulin were measured among 9716 Atherosclerosis Risk in Communities Study participants in 1990-1992 and 1996-1998. Percentage change in three filtration markers (eGFR on the basis of creatinine, eGFR on the basis of cystatin C, and 1/β2-microglobulin) individually and the average of percentage change across all three filtration markers were calculated. Cardiovascular events and deaths were ascertained from 1996 to 2011. Cox regression models were adjusted for established risk factors for cardiovascular disease and mortality and first measurement of eGFR on the basis of creatinine.
  
  
  RESULTS
  During a median follow-up of 14 years, there were 1922 cardiovascular events and 2285 deaths from any cause. Decline of >30% in each filtration marker was significantly associated with higher risk of mortality compared with stable kidney function (-9.9% to +9.9% change in the filtration marker) with hazard ratios (95% confidence intervals) of 1.91 (1.67 to 2.18) for eGFR on the basis of creatinine, 2.29 (1.99 to 2.63) for eGFR on the basis of cystatin C, and 2.48 (2.15 to 2.86) for 1/β2-microglobulin, with similar associations for cardiovascular disease. An average decline of >30% across the three markers was strongly associated with higher risk of all-cause mortality (hazard ratio, 2.82; 95% confidence interval, 2.42 to 3.29).
  
  
  CONCLUSIONS
  Kidney disease progression was assessed using >30% decline in eGFR on the basis of creatinine, eGFR on the basis of cystatin C, and 1/β2-microglobulin and average decline of >30% across the three filtration markers is strongly associated with risk of cardiovascular disease and death.
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; crebhol1@jhu.edu.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rebholz
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Divisions of Nephrology and.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Grams
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Inker
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Foster
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; and.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; and.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D001613:beta 2-Microglobulin; D003404:Creatinine
keywords: cardiovascular disease; creatinine; mortality
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