title: ADMA levels correlate with proteinuria, secondary amyloidosis, and endothelial dysfunction.
abstract: 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.
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.forename: Alper
authors.initials: A
authors.lastname: Sonmez
authors.forename: Mutlu
authors.initials: M
authors.lastname: Saglam
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Juan Jesus
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Kayser
authors.initials: K
authors.lastname: Caglar
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.forename: Erdinc
authors.initials: E
authors.lastname: Cakir
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Oguz
authors.forename: Abdulgaffar
authors.initials: A
authors.lastname: Vural
authors.forename: Mujdat
authors.initials: M
authors.lastname: Yenicesu
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Jonas
authors.initials: J
authors.lastname: Axelsson
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002908:Chronic Disease; D004727:Endothelium / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000453:epidemiology / Q000378:metabolism; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism*; D012307:Risk Factors
chemical_list: C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine