Advanced glycation urinary protein-bound biomarkers and severity of diabetic nephropathy in man

Melinda T. Coughlan, Sheila K. Patel, George Jerums, Sally A. Penfold, Tuong Vi Nguyen, Karly C. Sourris, Sianna Panagiotopoulos, Piyush M. Srivastava, Mark E. Cooper, Louise M. Burrell, Richard J. MacIsaac, Josephine M. Forbes

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30 Citations (Scopus)

Abstract

Background/Aims: The formation of advanced glycation end products (AGEs) is accelerated in patients with diabetic nephropathy. The aim of this study was to ascertain if the urinary excretion of proteins modified by advanced glycation can be used as biomarkers for albuminuria in individuals with type 1 or type 2 diabetes. Methods: Community-based patients with type 1 (n = 68) or type 2 diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital were classified as having normoalbuminuria (Normo, albumin excretion rate (AER) <20 μg/min), microalbuminuria (Micro, AER 20-200 μg/min) or macroalbuminuria (Macro, AER ≥200 μg/min). Serum and urine AGE-modified proteins were measured. Results: In patients with both type 1 diabetes and type 2 diabetes, there was a clear association between the degree of albuminuria and urinary AGE-modified proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary excretion of the AGE carboxymethyllysine correlated with AER, whereas patients with type 2 diabetes and macroalbuminuria had an increase in urinary methylglyoxal, an AGE intermediate. These changes were independent of isotopic glomerular filtration rate levels. Serum concentrations of AGEs or soluble receptor for AGEs were not consistently associated with albuminuria in either type 1 or type 2 diabetes. Conclusions: Urinary excretion of proteins modified by AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type 2 diabetes, warranting prospective investigation in larger diabetic cohorts. 

Original languageEnglish
Pages (from-to)347-355
Number of pages9
JournalAmerican Journal of Nephrology
Volume34
Issue number4
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Advanced glycation end products
  • Albuminuria
  • Carboxymethyllysine
  • Diabetic nephropathy
  • Methylglyoxal
  • Urinary biomarkers

Cite this

Coughlan, M. T., Patel, S. K., Jerums, G., Penfold, S. A., Nguyen, T. V., Sourris, K. C., Panagiotopoulos, S., Srivastava, P. M., Cooper, M. E., Burrell, L. M., MacIsaac, R. J., & Forbes, J. M. (2011). Advanced glycation urinary protein-bound biomarkers and severity of diabetic nephropathy in man. American Journal of Nephrology, 34(4), 347-355. https://doi.org/10.1159/000331064