title: Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD.
abstract: OBJECTIVE
  eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR).
  
  
  METHODS
  GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromsø Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR.
  
  
  RESULTS
  sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m(2); 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m(2); 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m(2); 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (-1.4 ml/min per 1.73 m(2); 95% CI, -2.1 to -0.6 per SD increase in sTNFR2, and -0.76 ml/min per 1.73 m(2); 95% CI, -1.4 to -0.1 per SD increase in log CRP).
  
  
  CONCLUSIONS
  eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR-related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies.
authors.affiliation: Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and jorgen.schei@unn.no.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Schei
authors.affiliation: Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and.
authors.forename: Vidar T N
authors.initials: VT
authors.lastname: Stefansson
authors.affiliation: Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and.
authors.forename: Ulla Dorte
authors.initials: UD
authors.lastname: Mathisen
authors.affiliation: Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and.
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Eriksen
authors.affiliation: Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and.
authors.forename: Marit D
authors.initials: MD
authors.lastname: Solbu
authors.affiliation: Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and Department of Nephrology, Oslo University Hospital, Oslo, Norway.
authors.forename: Trond G
authors.initials: TG
authors.lastname: Jenssen
authors.affiliation: Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and.
authors.forename: Toralf
authors.initials: T
authors.lastname: Melsom
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003287:Contrast Media / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005919:Glomerular Filtration Rate; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007472:Iohexol / Q000008:administration & dosage; D007668:Kidney / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D009664:Norway; D011237:Predictive Value of Tests; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D003287:Contrast Media; D055316:Cystatin C; D018836:Inflammation Mediators; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D007472:Iohexol; D005340:Fibrinogen; D002097:C-Reactive Protein; D003404:Creatinine
keywords: C-reactive protein; cardiovascular disease; chronic kidney disease; cystatin C; fibrinogen; glomerular filtration rate; humans; kidney function tests; tumor necrosis factor