2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007040461v1 19/2/388    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yilmaz, M. I. Articles by Axelsson, J. Search for Related Content PubMed PubMed Citation Articles by Yilmaz, M. I. Articles by Axelsson, J. Related Collections Related Article

ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction

Mahmut Ilker Yilmaz^*,, Alper Sonmez, Mutlu Saglam, Abdul R. Qureshi, Juan Jesus Carrero, Kayser Caglar^*, Tayfun Eyileten^*, Erdinc Cakir^||, Yusuf Oguz^*, Abdulgaffar Vural^*, Mujdat Yenicesu^*, Bengt Lindholm, Peter Stenvinkel and Jonas Axelsson

Departments of ^* Nephrology, Internal Medicine, Radiology, and ^|| Biochemistry, Gülhane School of Medicine, Etlik-Ankara, Turkey; and Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

Correspondence: Dr. Mahmut Ilker Yilmaz, Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, K56 Karolinska University Hospital Huddinge, Stockholm, Sweden 141 86. Phone +46-8-58582532; Fax +46-8-58582532; E-mail: mahmutiyilmaz{at}yahoo.com

Received for publication April 16, 2007. Accepted for publication August 3, 2007.

Asymmetric dimethyl-arginine (ADMA), a residue of the proteolysis of arginine-methylated proteins, is a potent inhibitor of nitric oxide synthesis. The increased protein turnover that accompanies proteinuric secondary amyloidosis may increase circulating levels of ADMA, and this may contribute to endothelial dysfunction. We performed a cross-sectional study of 121 nondiabetic proteinuric patients with normal GFR (including 39 patients with nephrotic-range proteinuria and secondary amyloidosis) and 50 age-, sex-, and BMI–matched healthy controls. The proteinuric patients had higher levels of serum ADMA, symmetric dimethyl-arginine (SDMA), high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment index) than controls. Compared with controls, brachial artery flow-mediated dilatation (FMD), serum L-Arginine, and the L-Arginine/ADMA ratio were significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA and SDMA levels and lower L-Arginine/ADMA ratios and FMD measurements (P < 0.001 for all). Finally, even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. We propose that ADMA synthesis may be increased in chronic kidney disease, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2008 19: A12. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673