Perkins, Bruce A., Rabbani, Naila, Weston, Andrew J., Ficociello, Linda H., Antonysunil, Adaikalakoteswari, Niewczas, Monika, Warram, James, Krolewski, Andrzej S. and Thornalley, Paul J. (2012) Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes. PLoS One, Vol.7 (No.4). e35655. doi:10.1371/journal.pone.0035655 ISSN 1932-6203.

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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 1st 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 GFRCYSTATIN 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 Nω-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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Diabetes, Blood proteins, Glycosylation, Oxidation, Nitration
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	2012
Dates:	Date Event 2012 Published
Volume:	Vol.7
Number:	No.4
Page Range:	e35655
DOI:	10.1371/journal.pone.0035655
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	1 August 2016
Date of first compliant Open Access:	1 August 2016
Funder:	National Institutes of Health (U.S.) (NIH), Joslin Diabetes Center, Canadian Diabetes Association (CDA), Banting and Best Diabetes Centre
Grant number:	DK041526 (NIH), DK067638 (NIH)

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