title: Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: a cross sectional study.
abstract: BACKGROUND
  Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.
  
  
  RESULTS
  Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005).
  
  
  CONCLUSIONS
  These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.
authors.affiliation: Division of Nephrology, Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States of America. bun.jim@nbhn.net
authors.forename: Belinda
authors.initials: B
authors.lastname: Jim
authors.forename: Mythili
authors.initials: M
authors.lastname: Ghanta
authors.forename: Andi
authors.initials: A
authors.lastname: Qipo
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.forename: Hillel W
authors.initials: HW
authors.lastname: Cohen
authors.forename: Maria
authors.initials: M
authors.lastname: Abadi
authors.forename: David B
authors.initials: DB
authors.lastname: Thomas
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C113267:nephrin