Serum levels of the advanced glycation end products Nepsilon-carboxymethyllysine and pentosidine are not influenced by treatment with the angiotensin receptor II type 1 blocker irbesartan in patients with type 2 diabetic nephropathy and hypertension

Nephron Clin Pract. 2008;108(4):c291-7. doi: 10.1159/000127838. Epub 2008 Apr 24.

Abstract

Background/aims: The aim of this post-hoc analysis of a prospective study in patients with type 2 diabetic nephropathy was to investigate whether treatment with the angiotensin II type 1 receptor blocker irbesartan leads to a reduction in the serum levels of the advanced glycation end products (AGEs) pentosidine and N(epsilon)-carboxymethyllysine (CML).

Methods: One hundred and ninety-six patients of the Irbesartan in Diabetic Nephropathy Trial cohort (mean age 61 +/- 6.5 years, 62 female, 134 male) with a mean estimated glomerular filtration rate of 47.7 ml/min were treated with irbesartan (n = 65), the calcium channel blocker amlodipine (n = 61) or by placebo (n = 70). Serum levels of pentosidine and CML were measured at baseline and after follow-up (23.4 months).

Results: Estimated glomerular filtration rate decreased in all groups by a mean of 8.6 ml/min. Serum levels of AGEs increased significantly (p < 0.001) during follow-up. After controlling for renal function and total protein concentration, changes were 53, 55, 50% for pentosidine and 29, 24, 23% for CML (irbesartan, amlodipine and placebo group, respectively). The increase was not significantly different between the treatment groups.

Conclusion: Irbesartan did not alter the increase in pentosidine and CML in serum of type 2 diabetic patients with progressive nephropathy. This finding suggests that angiotensin receptor blockade alone is insufficient to reduce serum levels of AGEs in diabetic nephropathy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amlodipine / therapeutic use
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Antihypertensive Agents / therapeutic use
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biphenyl Compounds / therapeutic use*
  • Calcium Channel Blockers / therapeutic use
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Glycation End Products, Advanced / blood*
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Irbesartan
  • Linear Models
  • Lysine / analogs & derivatives*
  • Lysine / blood
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • Tetrazoles / therapeutic use*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Calcium Channel Blockers
  • Glycation End Products, Advanced
  • Tetrazoles
  • Amlodipine
  • N(6)-carboxymethyllysine
  • Arginine
  • pentosidine
  • Irbesartan
  • Lysine