HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Temporal increases in urinary carboxymethyllysine correlate with albuminuria development in diabetes.

AbstractBACKGROUND/AIMS:
Advanced glycation end products (AGEs) mediate progressive tissue damage in diabetic nephropathy; however, their utility as a noninvasive reliable biomarker of progressive diabetic nephropathy remains to be determined. In this study, we investigated the temporal accumulation of the AGE carboxymethyllysine (CML) at various sites in a model of experimental diabetic nephropathy.
METHODS:
Diabetic rats were followed for 1, 4, 8, 16 and 32 weeks. Glomerular filtration rate and urinary albumin excretion were measured. CML was determined in the plasma, urine, renal cortical mitochondria and cytosol by an in-house ELISA. Gene expression of AGE receptors were quantified by real-time PCR and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by EIA.
RESULTS:
Four weeks after diabetes induction, urinary CML excretion was increased, which preceded the excretion of urinary albumin and continued to rise progressively until 32 weeks. Circulating, mitochondrial and cytosolic CML content and urinary excretion of 8-OHdG were increased 4 weeks after diabetes induction, but did not increase further with diabetes duration. Renal gene expression of AGE receptors was transiently upregulated at 1 week of diabetes, but this was not a sustained phenomenon.
CONCLUSIONS:
The most informative marker of progressive renal damage linked to the AGE pathway in experimental diabetic nephropathy is urinary excretion of CML, which now warrants clinical investigation as a potential noninvasive sensitive marker of progressive diabetic nephropathy.
AuthorsMelinda T Coughlan, Josephine M Forbes
JournalAmerican journal of nephrology (Am J Nephrol) Vol. 34 Issue 1 Pg. 9-17 ( 2011) ISSN: 1421-9670 [Electronic] Switzerland
PMID21654162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 S. Karger AG, Basel.
Chemical References
  • Biomarkers
  • Glycation End Products, Advanced
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Streptozocin
  • N(6)-carboxymethyllysine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Lysine
Topics
  • 8-Hydroxy-2'-Deoxyguanosine
  • Albuminuria (urine)
  • Animals
  • Biomarkers (blood, urine)
  • Cytosol (metabolism)
  • Deoxyguanosine (analogs & derivatives, urine)
  • Diabetes Mellitus, Experimental (metabolism)
  • Diabetes Mellitus, Type 1 (chemically induced, metabolism)
  • Diabetic Nephropathies (genetics, metabolism, urine)
  • Gene Expression
  • Glomerular Filtration Rate
  • Glycation End Products, Advanced (metabolism, urine)
  • Kidney Cortex (metabolism)
  • Lysine (analogs & derivatives, metabolism, urine)
  • Male
  • Mitochondria (metabolism)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic (genetics, metabolism)
  • Streptozocin
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: