Present study shows that there is a positive correlation between IMA and PTH (p = 0,01, r = 0,436), IMA and CRP (p = 0,007, r = 0,452) and ALP and IMA (p < 0,05, r = 0.268). Multiple regression analysis was run to predict IMA levels from PTH, CRP and creatinine the model statistically significantly predicted relation p < 0,05, R = 0,506, out of four two variables added statistically significant to the prediction, PTH (p = 0,006), CRP (p = 0,029). In this study, we showed for the first time that parathormone is associated with IMA independently of creatinine level.
Current research on non-traditional risk factors has revealed that oxidative stress is an important cardiovascular risk factor in uremic patients (11). Hemodialysis patients are characterized with imbalance between pro-oxidative products and anti-oxidative defense mechanisms which resulting increase at oxidative stress and deficient anti-oxidative defense. Anti-oxidant defense mechanisms such as superoxide dismutase, catalase, glutathione peroxidase is found impaired at the setting of CKD and HD. Increased ROS production and activation of enzymatic systems including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, lipoxygenase, uncoupled nitric oxide synthase (NOS) are the causes of exacerbated oxidative stress. Activation of transcription factors by OS causes expression of genes regulating proinflammatory cytokines and chemokines. There is a tight link between OS and inflammation which is associated with disease progression, poor outcomes, increase at risk of complications such as cardiovascular disease (2, 12, 13).
Oxidative stress and inflammation process are influenced by PTH. Dietary induced hyperparathyroidism causes inflammatory cytokine production increase at rats (5). Cheng et al. reported association between PTH and inflammatory markers including CRP at general population (4). Hyperparathyroidism has also been shown to play an important role in increasing oxidative stress in hemodialysis patients (14). Recently, IMA has been demonstrated as a novel oxidative stress biomarker in uremic patients (8, 15, 16).
Human serum albumin is a plasma protein which is affected by oxidative stress in HD patients. N terminus of the albumin which its first three amino acids consisting aspartate-alanine-histidine is the binding site for transitional metals including cobalt, nickel and copper. Free radicals, ischemia, hypoxia, inflammation, increased oxidative stress can cause degradation of this site decreasing its ability to bind metals thus resulting formation of IMA. (15, 17). Although IMA is first suggested as rapid and sensitive test for diagnosis of acute myocardial ischemia, recent studies show that its potential role as biomarker is not only limited to cardiac ischemia. (17, 18). In the setting of excessive oxidative stress and inflammation IMA is found increased at plethora of clinical conditions especially including ESRD (8, 19–23). HD and peritoneal dialysis patients have been shown to have higher serum IMA levels compared to renal transplantation patients and healthy subjects (16).
IMA is found increased at HD patients compared to control groups at previous studies (8, 24). Cichota et al. reported that CKD patients with anemia has higher IMA levels compared to healthy controls (p < 0,05) (15). Sharma et al. reported that IMA level can predict mortality in patients at transplantation candidate ESRD patients (16). We have shown for the first time that IMA level is associated with PTH levels independently of creatinine levels in ESRD patients. This may imply an important role in the pathophysiology of hyperparathyroidism-induced increased oxidative stress in HD patients. At our study ALP and IMA are found positively correlated (p < 0,05, r = 0,268), ALP may rise in hemodialysis patients due to hyperparathyroidism. In our study, the relationship between ALP elevation and IMA may be result of hyperparathyroidism effect.
In multiregression analysis, IMA was found to be associated with PTH and CRP independent of creatinine value. Previous studies investigating relation between high sensitive CRP (hs-CRP) and IMA at ESRD patients reported positive correlation between IMA and hs-CRP (25). At our study, there was a very strong correlation between CRP and IMA (p = 0,007, r = 0,452) and our study is the first study in the literature showing independent correlation between CRP and IMA at HD patients