Chronic kidney disease (CKD) is a newly recognized high-risk population for cardiovascular disease (CVD). The relative risk of death from myocardial infarction is 10–30 times higher in hemodialysis patients (CKD stage 5D) as compared to the general population. Atherosclerotic vascular changes are present in patients with CKD not yet treated with hemodialysis[3–5] as well as in hemodialysis patients. The risk for CVD increases in a stepwise manner as glomerular filtration rate (GFR) declines. The increased risk of CVD in reduced GFR may be explained at least partly by impairment of classical risk factors including hypertension, dyslipidemia, and glucose intolerance/insulin resistance. In addition, inflammation and increased oxidative stress[11,12] presumably contribute to the CKD-related excess risk for CVD.
Oxidative stress is determined by the balance between the production and elimination of reactive oxygen species (ROS). Since superoxide anion and other ROS are difficult to be evaluated reliably in clinical conditions due to their very short half-lives, more stable markers have been measured in biological specimens. For example, oxidative modifications of lipids, proteins, and nucleic acids can be evaluated by thiobarbituric acids-reactive substances (TBARS),[14,15] advanced oxidation protein products (AOPP), and 8-hydroxydeoxyguanodine (8-OHdG), respectively. In addition, proteins that are secreted into the circulation in response to oxidative stress may serve as the biomarkers for oxidative stress. Thioredoxin (TRX) is among such proteins. TRX is a 12 kD protein, secreted by most cell types, with a redox-active dithiol/disulfide in the active site consensus sequence: -Cys-Gly-Pro-Cys-, showing anti-oxidative properties. Plasma TRX levels are increased in response to oxidative stress as shown in experimental and human studies.[19–21] Also, serum TRX is known to be elevated in patients with increased oxidative stress, such as pancreatic cancer, hepatitis C virus infection, severe burn injury, acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, heart failure, steato hepatitis, and interstitial lung disease.
Uremia is considered as pro-oxidant state.[11,30] Previous studies demonstrated the elevated levels of biomarkers for oxidative modification of lipids and proteins in dialysis patients, and in advanced stages of CKD prior to renal replacement therapy. So far, however, information is limited regarding possible changes in inflammation and oxidative stress among subjects with mild reduction of renal function.[33–35]
In the present study, we measured C-reactive protein (CRP) and TRX as biomarkers for inflammation and oxidative stress, and compared them between subjects with normal and mildly reduced glomerular filtration rate (GFR).
BMC Nephrology. 2010;11:7 © 2010 Tsuchikura et al.; licensee BioMed Central, Ltd.
Cite this: Serum C-reactive Protein and Thioredoxin Levels in Subjects with Mildly Reduced Glomerular Filtration Rate - Medscape - Apr 27, 2010.