title: Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review.
abstract: Fibrosis is the unifying pathway leading to chronic kidney disease. Identifying biomarkers of fibrosis may help predict disease progression.
  
  
  
  We performed a systematic review to evaluate the reliability of blood and urine biomarkers in identifying fibrosis on biopsy as well as predicting renal outcomes. Using MEDLINE and EMBASE, a two-stage search strategy was implemented. Stage I identified a library of biomarkers correlating with fibrosis on biopsy. Stage II evaluated the association between biomarkers identified in stage I, and renal outcomes. Only biomarkers with moderate positive correlation with fibrosis (r > 0.40) or acceptable area under the curve (AUC >0.65) advanced to stage II.
  
  
  
  Stage I identified 17 studies and 14 biomarkers. Five biomarkers met criteria to advance to stage II, but only three were independently associated with renal outcomes. Transforming growth factor β (TGF-β) correlated with fibrosis (r = 0.60), and was associated with 1.7-3.9 times the risk of worsening renal function in 426 patients. Monocyte chemoattractant protein-1 (MCP-1) diagnosed fibrosis with AUC of 0.66 and was associated with 2.3-11.0 times the risk of worsening renal function in 596 patients. Matrix metalloproteinase-2 (MMP-2) correlated with fibrosis (r = 0.41), and was associated with 2.5 times the risk of worsening renal function.
  
  
  
  Given the heterogeneity of the data due to diverse patient populations along with differing renal outcomes, a meta-analysis could not be conducted. Nonetheless we can conclude from the published data that TGF-β, MCP-1 and MMP-2 may identify patients at risk for renal fibrosis and hence worse renal outcomes.
authors.affiliation: Program of Applied Translational Research, Department of Medicine, Yale University, School of Medicine, New Haven, CT, USA.|Section of Nephrology, Yale University School of Medicine, 60 Temple Street, Suite 6C, New Haven, CT, 06510, USA.
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Mansour
authors.affiliation: Program of Applied Translational Research, Department of Medicine, Yale University, School of Medicine, New Haven, CT, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Puthumana
authors.affiliation: Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
authors.affiliation: Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gentry
authors.affiliation: Program of Applied Translational Research, Department of Medicine, Yale University, School of Medicine, New Haven, CT, USA. chirag.parikh@yale.edu.|Section of Nephrology, Yale University School of Medicine, 60 Temple Street, Suite 6C, New Haven, CT, 06510, USA. chirag.parikh@yale.edu.|Veterans Affairs Connecticut Healthcare System, New Haven, CT, USA. chirag.parikh@yale.edu.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism*; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011379:Prognosis; D015203:Reproducibility of Results; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016212:Transforming Growth Factor beta; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Biomarkers; Chronic kidney disease; Fibrosis; Outcomes; Renal biopsy; Renal disease progression