High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes.
Adult
Advanced Oxidation Protein Products
/ urine
Albuminuria
/ complications
Case-Control Studies
Chromatography, Liquid
Creatinine
/ blood
Diabetes Mellitus, Type 1
/ complications
Diabetic Nephropathies
/ etiology
Female
Glomerular Filtration Rate
Glycation End Products, Advanced
/ urine
Humans
Male
Middle Aged
Prospective Studies
Tandem Mass Spectrometry
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 07 2020
29 07 2020
Historique:
received:
10
02
2020
accepted:
10
06
2020
entrez:
31
7
2020
pubmed:
31
7
2020
medline:
18
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32728119
doi: 10.1038/s41598-020-69350-y
pii: 10.1038/s41598-020-69350-y
pmc: PMC7391737
doi:
Substances chimiques
Advanced Oxidation Protein Products
0
Glycation End Products, Advanced
0
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12709Références
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