title: Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2 Concentrations Are Related to Renal Function in Two Population-Based Cohorts.
abstract: BACKGROUND
  An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population.
  
  
  METHODS
  Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated.
  
  
  RESULTS
  In both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed.
  
  
  CONCLUSIONS
  Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Hennings
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Hannemann
authors.affiliation: Institute of Physiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rettig
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dörr
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany.|Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.|DZD (German Centre for Diabetes Research), partner site Greifswald, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Department of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
authors.affiliation: Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany.|Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000032:analysis; D042702:Angiopoietin-2 / Q000097:blood*; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D042787:Receptor, TIE-2 / Q000097:blood*
chemical_list: D000418:Albumins; D042702:Angiopoietin-2; D055316:Cystatin C; D003404:Creatinine; D042787:Receptor, TIE-2