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

Perkins, BA, Rabbani, N, Weston, A, Antonysunil, A ORCID: https://orcid.org/0000-0003-2974-3388, Lee, JA, Lovblom, LE, Cardinez, N and Thornalley, PJ, 2020. High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes. Scientific Reports, 10: 12709. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal article
Publication Title:	Scientific Reports
Creators:	Perkins, B.A., Rabbani, N., Weston, A., Antonysunil, A., Lee, J.A., Lovblom, L.E., Cardinez, N. and Thornalley, P.J.
Publisher:	Nature Publishing Group
Date:	29 July 2020
Volume:	10
ISSN:	2045-2322
Identifiers:	Number Type 1332421 Other 10.1038/s41598-020-69350-y DOI
Rights:	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	15 Jun 2020 14:36
Last Modified:	31 May 2021 15:07
URI:	https://irep.ntu.ac.uk/id/eprint/39996

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