SP349DOES NITRIC OXIDE PREVENT THE DEVELOPMENT OF ATHEROSCLEROSIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE? - THE IMPACT OF ATHEROSCLEROTIC CHANGES IN THE COMMON CAROTID ARTERY

Abstract

Introduction and Aims: The aim of the study was to evaluate the association between markers of oxidative stress, endothelial dysfunction, inflammation, bone turnover and the carotid artery intima-media thickness (CCA-IMT) measured by ultrasound in chronic kidney disease (CKD) patients. Methods: The study included 62 patients (27 women and 35 men, mean age 63+/-16) with stage 5 CKD, including 42 hemodialyzed and 20 pre-dialysis. The examined parameters included CCA-IMT, and plasma/serum concentrations of nitric oxide (NO), free reduced glutathione (GSH), hydrogen sulfide (H2S), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, thrombomodulin (TM), calcium (Ca), phosphate (Pi), iPTH, fibroblast growth factor 23 (FGF 23), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC), C-reactive protein (CRP), tumor necrosis factor receptor II (TNFR II), and transforming growth factor-β1 (TGFβ1). Framingham risk score was calculated. Results: Median NO concentrations were 5.40 (IQR: 4.52-6.99) μmol/l and did not differ between hemodialyzed and pre-dialysis patients (p=0.8). In simple analysis, NO concentrations were positively correlated with serum creatinine, iPTH, Pi and Ca x Pi, FGF 23, TNFR II, and TM. NO (log-transformed) significantly predicted CCA-IMT in simple analysis (R=0.39; p=0.014) and in multiple analysis (beta=0.34+/-0.16; p=0.036) independently of log(Framingham score), log(CRP), log(serum creatinine) and log (iPTH). Moreover, patients with atherosclerotic plaques detected in CCA had higher NO concentrations: 5.84 (5.05-7.16) versus 4.88 (4.35-5.67) μmol/l (p=0.021). Conclusions: Higher nitric oxide levels were found in patients with more advanced kidney disease, with more severe mineral-bone disorders, and more advanced endothelial dysfunction. NO concentrations were associated with atherosclerotic changes in CCA in CKD patients independently of classical cardiovascular risk factors, inflammation and secondary hyperparathyroidism. Our study suggests that the increased production of nitric oxide may be an early compensatory mechanism in the damaged vessel wall in uremic patients against the development of atherosclerosis.