Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.

<h4>Objective</h4>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.<h4>Methods</h4...

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Autores principales:	Bruce A Perkins, Naila Rabbani, Andrew Weston, Linda H Ficociello, Antonysunil Adaikalakoteswari, Monika Niewczas, James Warram, Andrzej S Krolewski, Paul Thornalley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4c707316da3741ce90e5ab3eb0f0d13f
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spelling	oai:doaj.org-article:4c707316da3741ce90e5ab3eb0f0d13f2021-11-18T07:20:57ZSerum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.1932-620310.1371/journal.pone.0035655https://doaj.org/article/4c707316da3741ce90e5ab3eb0f0d13f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558190/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.Bruce A PerkinsNaila RabbaniAndrew WestonLinda H FicocielloAntonysunil AdaikalakoteswariMonika NiewczasJames WarramAndrzej S KrolewskiPaul ThornalleyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35655 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bruce A Perkins Naila Rabbani Andrew Weston Linda H Ficociello Antonysunil Adaikalakoteswari Monika Niewczas James Warram Andrzej S Krolewski Paul Thornalley Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
description	<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
format	article
author	Bruce A Perkins Naila Rabbani Andrew Weston Linda H Ficociello Antonysunil Adaikalakoteswari Monika Niewczas James Warram Andrzej S Krolewski Paul Thornalley
author_facet	Bruce A Perkins Naila Rabbani Andrew Weston Linda H Ficociello Antonysunil Adaikalakoteswari Monika Niewczas James Warram Andrzej S Krolewski Paul Thornalley
author_sort	Bruce A Perkins
title	Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
title_short	Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
title_full	Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
title_fullStr	Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
title_full_unstemmed	Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
title_sort	serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4c707316da3741ce90e5ab3eb0f0d13f
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Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.

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