Increased phagocytic nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production in patients with early chronic kidney disease.
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.


CONCLUSIONS
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.
Fortuño
Ana
A
Division of Cardiovascular Sciences, Centre for Applied Medical Research, and Department of Internal Medicine, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain.
Beloqui
Oscar
O
San José
Gorka
G
Moreno
María U
MU
Zalba
Guillermo
G
Díez
Javier
J
D000098:Acetophenones / Q000494:pharmacology; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D002908:Chronic Disease; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D010586:Phagocytes / Q000201:enzymology* / Q000502:physiology; D012306:Risk; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014463:Ultrasonography
D000098:Acetophenones; D004791:Enzyme Inhibitors; D007328:Insulin; D013481:Superoxides; C056165:acetovanillone; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate