Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation

Paul J. Beisswenger, Scott K. Howell, Greg Russell, Michael E. Miller, Stephen S. Rich, Michael Mauer

Research output: Contribution to journalArticle

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Abstract

Increased advanced glycation endproducts (AGEs) and oxidation products (OPs) have been proposed as pathogenic for diabetic nephropathy (DN). We investigated the relationship between AGEs and OPs measured in different plasma and urine preparations, and progression of DN in 103 young, normoalbuminuric, normotensive participants with type 1 diabetes in the Natural History of Diabetic Nephropathy Study. The primary endpoint was electron microscopy-measured change in glomerular basement membrane (GBM) width from baseline to 5 years; change in mesangial fractional volume was a secondary endpoint. Fast progressors (FP) were defined as the upper quartile (n = 24) of rate of GBM thickening; slow progressors (SP) were the remainder (n = 79). Four AGEs [3-deoxyglucosone and methylglyoxal hydroimidazolones (DG3H1, MGH1) and carboxymethyl and ethyl lysine (CML, CEL)], and two oxidation products methionine sulfoxide and aminoadipic acid were measured by liquid chromatography, triple quadrupole mass spectrometry. Measurements were done on 10 K plasma filtrates and plasma proteolytic digests (PPD) at year 5, and at four time points over 5 years for urinary 10 K filtrates. Urinary filtrate CEL levels were significantly higher in FP, but not after adjustment for HbA1c, sex, and duration of diabetes. MGHI, CEL, and CML plasma filtrate levels were significantly higher in FP relative to SP (p < 0.05). In PPD, only MGHI showed borderline significantly higher levels in FP relative to SP (p = 0.067), while no other product showed correlation. AGE and OP measurements were not correlated with mesangial expansion. In plasma filtrates, HbA1c at year 5 accounted for 4.7 % of the variation in GBM width. The proportion of variation in GBM width was increased to 11.6 % when MGHI, CEL, and CML were added to the model (6.9 % increase).

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalAmino Acids
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2014

Fingerprint

Diabetic Nephropathies
Glomerular Basement Membrane
Urine
Plasmas
Emitter coupled logic circuits
Oxidation
Medical problems
Pyruvaldehyde
Liquid chromatography
Type 1 Diabetes Mellitus
Liquid Chromatography
Electron microscopy
Mass spectrometry
Mass Spectrometry
Electron Microscopy
Acids
Basement Membrane

Keywords

  • Advanced glycation endproducts
  • Biomarkers
  • Diabetic complications
  • Diabetic nephropathy
  • Glycation
  • Mass spectrometry
  • Oxidation
  • Oxidation end-products

Cite this

Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation. / Beisswenger, Paul J.; Howell, Scott K.; Russell, Greg; Miller, Michael E.; Rich, Stephen S.; Mauer, Michael.

In: Amino Acids, Vol. 46, No. 2, 01.02.2014, p. 311-319.

Research output: Contribution to journalArticle

Beisswenger, Paul J. ; Howell, Scott K. ; Russell, Greg ; Miller, Michael E. ; Rich, Stephen S. ; Mauer, Michael. / Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation. In: Amino Acids. 2014 ; Vol. 46, No. 2. pp. 311-319.
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