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.

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.

• Authors: Martin Busch, Sybille Franke, Gunter Wolf, Richard D Rohde, Günter Stein, Collaborative Study Group
• Journal: Nephron. Clinical practice (Nephron Clin Pract) Vol. 108 Issue 4 Pg. c291-7 ( 2008) ISSN: 1660-2110 [Electronic] Switzerland
• PMID: 18434751 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright 2008 S. Karger AG, Basel.

Chemical References

• 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

Topics

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