title: Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 Å or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state.
  
  
  METHODS
  Excretion of IgG, ceruloplasmin, transferrin, albumin, α2-macroglobulin with a large molecular radius of 88 Å and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio < 15 mg/g) with hypertension and nondiabetes mellitus (group hypertension, n = 32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n = 52) and type 2 diabetes mellitus and hypertension (group Both, n =45), and in age-matched controls (n = 72).
  
  
  RESULTS
  Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary α2-macroglobulin did not differ among the four groups.
  
  
  CONCLUSIONS
  These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in intraglomerular hydraulic pressure.
authors.affiliation: aDepartment of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata bDepartment of Clinical Laboratory Medicine, Juntendo University School of Medicine, Tokyo cDepartment of Endocrinology and Metabolism, Sanjo General Hospital, Niigata, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Ohara
authors.forename: Osamu
authors.initials: O
authors.lastname: Hanyu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Seiki
authors.initials: S
authors.lastname: Ito
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000737:chemistry / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology / Q000652:urine*; D007074:Immunoglobulin G / Q000737:chemistry / Q000652:urine*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000503:physiopathology; D007684:Kidney Tubules / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011312:Pressure; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D014168:Transferrin / Q000737:chemistry / Q000652:urine*
chemical_list: D000118:Acetylglucosaminidase; D002570:Ceruloplasmin; D006442:Glycated Hemoglobin; D007074:Immunoglobulin G; D014168:Transferrin; C517652:hemoglobin A1c protein, human