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.
OBJECTIVE
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.


CONCLUSIONS
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.
Busch
Martin
M
Department of Internal Medicine III, University of Jena, Jena, Germany. martin.busch@med.uni-jena.de
Franke
Sybille
S
Wolf
Gunter
G
Rohde
Richard D
RD
Stein
Günter
G
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D000077405:Irbesartan; D016014:Linear Models; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013777:Tetrazoles / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D017127:Glycation End Products, Advanced; D013777:Tetrazoles; D017311:Amlodipine; C048496:N(6)-carboxymethyllysine; D001120:Arginine; C062187:pentosidine; D000077405:Irbesartan; D008239:Lysine