title: Biomarkers of cardiovascular stress and incident chronic kidney disease.
abstract: BACKGROUND
  Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community.
  
  
  METHODS
  Plasma GDF-15, sST2, and hsTnI concentrations were measured in 2614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995-1998). Associations of biomarkers with incident chronic kidney disease [CKD, eGFR <60 mL · min(-1) · (1.73 m(2)) (-1), n = 276], microalbuminuria (urinary albumin to creatinine ratio ≥25 mg/g in women and 17 mg/g in men, n = 191), and rapid decline in renal function [decline in eGFR ≥3 mL · min(-1) · (1.73 m(2)) (-1) per year, n = 237], were evaluated using multivariable logistic regression; P < 0.006 was considered statistically significant in primary analyses.
  
  
  RESULTS
  Participants were followed over a mean of 9.5 years. Higher plasma GDF-15 was associated with incident CKD [multivariable-adjusted odds ratio (OR) 1.9 per 1-U increase in log-GDF-15, 95% CI 1.6-2.3, P < 0.0001] and rapid decline in renal function (OR, 1.6; 95% CI, 1.3-1.8; P < 0.0001). GDF-15, sST2, and hsTnI had suggestive associations with incident microalbuminuria but did not meet the prespecified P-value threshold after multivariable adjustment. Adding plasma GDF-15 to clinical covariates improved risk prediction of incident CKD: the c-statistic increased from 0.826 to 0.845 (P = 0.0007), and categorical net reclassification was 6.3% (95% CI, 2.7-9.9%).
  
  
  CONCLUSIONS
  Higher circulating GDF-15 is associated with incident renal outcomes and improves risk prediction of incident CKD. These findings may provide insights into the mechanisms of renal injury.
authors.affiliation: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA;
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ho
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D015994:Incidence; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007677:Kidney Function Tests; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface; D019210:Troponin I