BACKGROUND: Oxidative stress has been implicated in the pathogenesis of atherosclerosis that develops in patients with advanced chronic kidney disease (CKD). This study was designed to investigate whether a relationship exists between phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide anion (*O2-) production and subclinical atherosclerosis in patients with early CKD. METHODS: Superoxide production was assayed by chemiluminescence under baseline and stimulated conditions on mononuclear cells obtained from asymptomatic patients with stage 1 to 2 CKD (N=22) and healthy controls (N=21). Ultrasonographic determination of carotid intima-media thickness (IMT) was used to assess the presence of atherosclerosis. RESULTS: Although there were no differences in baseline *O2- production between controls and patients, the *O2- production in phorbol myristate acetate-stimulated mononuclear cells was increased (P<0.05) in patients compared with controls. The phorbol myristate acetate-induced *O2- production was completely abolished by apocynin, a specific inhibitor of NADPH oxidase. A direct correlation (r=0.441, P<0.05) was found between plasma insulin levels and NADPH oxidase-mediated *O2- production in patients. Carotid IMT was higher (P<0.005) in patients than in controls. Carotid IMT values above the upper normal limit in controls were found in 70% and 40% of patients with increased or normal NADPH oxidase-mediated *O2- production, respectively. CONCLUSION: Generation of *O2- that is mainly dependent on NADPH oxidase is abnormally enhanced in patients with early CKD. It is suggested that this alteration could be related to the development of subclinical atherosclerosis in these patients.
BACKGROUND: Oxidative stress has been implicated in the pathogenesis of atherosclerosis that develops in patients with advanced chronic kidney disease (CKD). This study was designed to investigate whether a relationship exists between phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide anion (*O2-) production and subclinical atherosclerosis in patients with early CKD. METHODS:Superoxide production was assayed by chemiluminescence under baseline and stimulated conditions on mononuclear cells obtained from asymptomatic patients with stage 1 to 2 CKD (N=22) and healthy controls (N=21). Ultrasonographic determination of carotid intima-media thickness (IMT) was used to assess the presence of atherosclerosis. RESULTS: Although there were no differences in baseline *O2- production between controls and patients, the *O2- production in phorbol myristate acetate-stimulated mononuclear cells was increased (P<0.05) in patients compared with controls. The phorbol myristate acetate-induced *O2- production was completely abolished by apocynin, a specific inhibitor of NADPH oxidase. A direct correlation (r=0.441, P<0.05) was found between plasma insulin levels and NADPH oxidase-mediated *O2- production in patients. Carotid IMT was higher (P<0.005) in patients than in controls. Carotid IMT values above the upper normal limit in controls were found in 70% and 40% of patients with increased or normal NADPH oxidase-mediated *O2- production, respectively. CONCLUSION: Generation of *O2- that is mainly dependent on NADPH oxidase is abnormally enhanced in patients with early CKD. It is suggested that this alteration could be related to the development of subclinical atherosclerosis in these patients.
Authors: Mahmood Rasool; Muhammad Abdul Basit Ashraf; Arif Malik; Sulayman Waquar; Shahida Aziz Khan; Mahmood Husain Qazi; Waseem Ahmad; Muhammad Asif; Sami Ullah Khan; Ahmad Zaheer; Muther Mansoor Qaisrani; Abdul Rehman Khan; Aamir Iqbal; Amir Raza; Saima Iram; Kashif Kamran; Asim Iqbal; Mohammad Zahid Mustafa; Hani Choudhry; Mazin A Zamzami; Wesam H Abdulaal; Mohammad Sarwar Jamal Journal: PLoS One Date: 2017-02-08 Impact factor: 3.240