High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes

<div><p>Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type...

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التفاصيل البيبلوغرافية
المؤلف الرئيسي: Bruce A. Perkins (8630269) (author)
مؤلفون آخرون: Naila Rabbani (291722) (author), Andrew Weston (63123) (author), Antonysunil Adaikalakoteswari (325054) (author), Justin A. Lee (18595231) (author), Leif E. Lovblom (18595234) (author), Nancy Cardinez (5154764) (author), Paul J. Thornalley (291723) (author)
منشور في: 2020
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author Bruce A. Perkins (8630269)
author2 Naila Rabbani (291722)
Andrew Weston (63123)
Antonysunil Adaikalakoteswari (325054)
Justin A. Lee (18595231)
Leif E. Lovblom (18595234)
Nancy Cardinez (5154764)
Paul J. Thornalley (291723)
author2_role author
author
author
author
author
author
author
author_facet Bruce A. Perkins (8630269)
Naila Rabbani (291722)
Andrew Weston (63123)
Antonysunil Adaikalakoteswari (325054)
Justin A. Lee (18595231)
Leif E. Lovblom (18595234)
Nancy Cardinez (5154764)
Paul J. Thornalley (291723)
author_role author
dc.creator.none.fl_str_mv Bruce A. Perkins (8630269)
Naila Rabbani (291722)
Andrew Weston (63123)
Antonysunil Adaikalakoteswari (325054)
Justin A. Lee (18595231)
Leif E. Lovblom (18595234)
Nancy Cardinez (5154764)
Paul J. Thornalley (291723)
dc.date.none.fl_str_mv 2020-07-29T09:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-020-69350-y
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/High_fractional_excretion_of_glycation_adducts_is_associated_with_subsequent_early_decline_in_renal_function_in_type_1_diabetes/25879570
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Medical biochemistry and metabolomics
Whiskey distillery waste streams
Pot ale liquid residue
Anaerobic digestion (AD)
Response surface methodology (RSM)
Protein glycation
Diabetic nephropathy
Type 1 diabetes (T1DM)
dc.title.none.fl_str_mv High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case–control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC–MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-020-69350-y" target="_blank">https://dx.doi.org/10.1038/s41598-020-69350-y</a></p>
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identifier_str_mv 10.1038/s41598-020-69350-y
network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/25879570
publishDate 2020
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spelling High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetesBruce A. Perkins (8630269)Naila Rabbani (291722)Andrew Weston (63123)Antonysunil Adaikalakoteswari (325054)Justin A. Lee (18595231)Leif E. Lovblom (18595234)Nancy Cardinez (5154764)Paul J. Thornalley (291723)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsWhiskey distillery waste streamsPot ale liquid residueAnaerobic digestion (AD)Response surface methodology (RSM)Protein glycationDiabetic nephropathyType 1 diabetes (T1DM)<div><p>Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case–control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC–MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-020-69350-y" target="_blank">https://dx.doi.org/10.1038/s41598-020-69350-y</a></p>2020-07-29T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-020-69350-yhttps://figshare.com/articles/journal_contribution/High_fractional_excretion_of_glycation_adducts_is_associated_with_subsequent_early_decline_in_renal_function_in_type_1_diabetes/25879570CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258795702020-07-29T09:00:00Z
spellingShingle High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
Bruce A. Perkins (8630269)
Biomedical and clinical sciences
Clinical sciences
Medical biochemistry and metabolomics
Whiskey distillery waste streams
Pot ale liquid residue
Anaerobic digestion (AD)
Response surface methodology (RSM)
Protein glycation
Diabetic nephropathy
Type 1 diabetes (T1DM)
status_str publishedVersion
title High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
title_full High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
title_fullStr High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
title_full_unstemmed High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
title_short High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
title_sort High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
topic Biomedical and clinical sciences
Clinical sciences
Medical biochemistry and metabolomics
Whiskey distillery waste streams
Pot ale liquid residue
Anaerobic digestion (AD)
Response surface methodology (RSM)
Protein glycation
Diabetic nephropathy
Type 1 diabetes (T1DM)