Cargando…

Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes

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 sele...

Descripción completa

Detalles Bibliográficos
Autores principales: Perkins, Bruce A., Rabbani, Naila, Weston, Andrew, Ficociello, Linda H., Adaikalakoteswari, Antonysunil, Niewczas, Monika, Warram, James, Krolewski, Andrzej S., Thornalley, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338454/
https://www.ncbi.nlm.nih.gov/pubmed/22558190
http://dx.doi.org/10.1371/journal.pone.0035655
_version_ 1782231193520963584
author Perkins, Bruce A.
Rabbani, Naila
Weston, Andrew
Ficociello, Linda H.
Adaikalakoteswari, Antonysunil
Niewczas, Monika
Warram, James
Krolewski, Andrzej S.
Thornalley, Paul
author_facet Perkins, Bruce A.
Rabbani, Naila
Weston, Andrew
Ficociello, Linda H.
Adaikalakoteswari, Antonysunil
Niewczas, Monika
Warram, James
Krolewski, Andrzej S.
Thornalley, Paul
author_sort Perkins, Bruce A.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3338454
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-33384542012-05-03 Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes Perkins, Bruce A. Rabbani, Naila Weston, Andrew Ficociello, Linda H. Adaikalakoteswari, Antonysunil Niewczas, Monika Warram, James Krolewski, Andrzej S. Thornalley, Paul PLoS One Research Article 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. Public Library of Science 2012-04-25 /pmc/articles/PMC3338454/ /pubmed/22558190 http://dx.doi.org/10.1371/journal.pone.0035655 Text en Perkins et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Perkins, Bruce A.
Rabbani, Naila
Weston, Andrew
Ficociello, Linda H.
Adaikalakoteswari, Antonysunil
Niewczas, Monika
Warram, James
Krolewski, Andrzej S.
Thornalley, Paul
Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338454/
https://www.ncbi.nlm.nih.gov/pubmed/22558190
http://dx.doi.org/10.1371/journal.pone.0035655
work_keys_str_mv AT perkinsbrucea serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT rabbaninaila serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT westonandrew serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT ficociellolindah serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT adaikalakoteswariantonysunil serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT niewczasmonika serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT warramjames serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT krolewskiandrzejs serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes
AT thornalleypaul serumlevelsofadvancedglycationendproductsandothermarkersofproteindamageinearlydiabeticnephropathyintype1diabetes