title: Serum Inflammatory and Immune Mediators Are Elevated in Early Stage Diabetic Nephropathy.
abstract: BACKGROUND
  Diabetes is the leading cause of end stage renal disease (ESRD) in the United States, representing 44% of incident cases [1]. In this study, serum and peripheral blood collected from diabetic patients in five stages of chronic kidney disease (CKD), as defined by glomerular filtration rate (GFR), were compared to healthy (non-CKD) subjects.
  
  
  METHODS
  Serum samples were analyzed for 39 inflammatory or immune mediator protein levels and peripheral blood samples were analyzed for expression of 35 gene transcripts.
  
  
  RESULTS
  In serum, MCP-1, FGF-2, VEGF, and EGF levels were elevated above controls at all stages of DN. Five mediator levels, GM-CSF, IL-1α, IL-1RA, IL-6, and MIP1β increased with disease progression until stage 4-5, at which point a decrease was observed paralleling a loss of functional renal mass that occurs in late stage CKD. Five mediator levels: GRO, IFNγ, MDC, Eotaxin, and G-CSF significantly differed from controls at one or more stages without apparent correlation with disease stage. Only a single mediator, sIL2RA, exhibited a linear increase with disease severity consistent with declining GFR. In peripheral blood, the transcript level of seven mediators, ICAM1, TNF-α, TGF-β, IL-8, IL17RA, IFNγ, and MYD88 were significantly elevated at all disease stages as compared to control.
  
  
  CONCLUSIONS
  Statistically significant differences in protein and transcripts levels between diseased and control can be detected in serum and peripheral blood utilizing high content profiling. These changes occur as early as stage 1-2 before a significant decline in renal function.
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perlman
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Chevalier
authors.affiliation: Janssen Research and Development, Spring House, PA, USA pwilkins@its.jnj.com.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wilkinson
authors.affiliation: Janssen Research and Development, Spring House, PA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Parker
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Levine
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: Betty Jo
authors.initials: BJ
authors.lastname: Sloan
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Gong
authors.affiliation: The Rogosin Institute, New York, NY, USA Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell, New York, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Sherman
authors.affiliation: Janssen Research and Development, Spring House, PA, USA.
authors.forename: Francis X
authors.initials: FX
authors.lastname: Farrell
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003710:Demography; D003928:Diabetic Nephropathies / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000235:genetics; D012720:Severity of Illness Index; D012995:Solubility
chemical_list: C507763:IL1RN protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger