title: Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
abstract: OBJECTIVE
  To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed "early GFR decline") in patients with type 1 diabetes.
  
  
  METHODS
  From the 1(st) Joslin Kidney Study, we selected 30 patients with longstanding normoalbuminuria and 55 patients with new onset microalbuminuria. Patients with microalbuminuria had 8-12 years follow-up during which 33 had stable GFR and 22 early GFR decline. Mean baseline GFR(CYSTATIN C) was similar between the three groups. Glycation, oxidation and nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometry using the most reliable methods currently available.
  
  
  RESULTS
  Though none were significantly different between patients with microalbuminuria with stable or early GFR decline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared to normoalbuminuria controls. Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increased in microalbuminuria. The most profound differences were of N-formylkynurenine (NFK) protein adduct residue and N(ω)-carboxymethylarginine (CMA) free adduct in which levels were markedly lower in microalbuminuria (P<0.001 for both).
  
  
  CONCLUSIONS
  Complex processes influence levels of plasma protein damage and related proteolysis product free adducts in type 1 diabetes and microalbuminuria. The effects observed point to the possibility that patients who have efficient mechanisms of disposal of damaged proteins might be at an increased risk of developing microalbuminuria but not early renal function decline. The findings support the concept that the mechanisms responsible for microalbuminuria may differ from the mechanisms involved in the initiation of early renal function decline.
authors.affiliation: Division of Endocrinology, University of Toronto, Toronto, Canada. bruce.perkins@uhn.on.ca
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Perkins
authors.forename: Naila
authors.initials: N
authors.lastname: Rabbani
authors.forename: Andrew
authors.initials: A
authors.lastname: Weston
authors.forename: Linda H
authors.initials: LH
authors.lastname: Ficociello
authors.forename: Antonysunil
authors.initials: A
authors.lastname: Adaikalakoteswari
authors.forename: Monika
authors.initials: M
authors.lastname: Niewczas
authors.forename: James
authors.initials: J
authors.lastname: Warram
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
authors.forename: Paul
authors.initials: P
authors.lastname: Thornalley
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002853:Chromatography, Liquid; D055316:Cystatin C / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D055316:Cystatin C; D017127:Glycation End Products, Advanced; C408696:N(omega)-carboxymethylarginine; C007772:N'-formylkynurenine; D007737:Kynurenine; D001120:Arginine