Perkins, BA;
Rabbani, N;
Weston, A;
Adaikalakoteswari, A;
Lee, JA;
Lovblom, LE;
Cardinez, N;
(2020)
High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes.
Scientific Reports
, 10
, Article 12709. 10.1038/s41598-020-69350-y.
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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 withT1DM with and without early decline inGFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline inGFR.We recruited patients withT1DM and normoalbuminuria (NA) (n= 30) or new onset MA with and without earlyGFR 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 inGFR, compared to patients with stableGFR (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 inGFR, compared to those with stableGFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with earlyGFR decline is likely involved.We conclude that higher fractional excretions of glycation adducts are potential biomarkers for earlyGFR decline inT1DM 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.
| Type: | Article |
|---|---|
| Title: | High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-020-69350-y |
| Publisher version: | https://doi.org/10.1038/s41598-020-69350-y |
| Language: | English |
| Additional information: | 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/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10107767 |
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