End stage renal disease (ESRD) patients have 10 times higher risk for developing cardiovascular disease (CVD) compared to control groups (1). It has been suggested that oxidative stress and inflammation are important contributors at pathophysiological process of development of CVD at HD patients recent years (1, 2, 3, 4).
Chronic Kidney Disease (CKD) is characterized with increased oxidative stress (OS), chronic inflammation and endothelial dysfunction which entails progression of kidney injury and systemic complications of CKD including especially CVD (4). Oxidative stress is more severe at ESRD patients receiving maintenance HD in particular (5). OS is also found increased in early stages of CKD (6). OS increase at CKD occurs by disruption of the balance between oxidative products and antioxidant defense mechanisms which includes upregulation and activation of enzymatic pathways such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, lipoxygenase, uncoupled nitric oxide synthase (NOS) and the mitochondrial respiratory chain resulting production of oxidative molecules reactive oxygen species (ROS) and nitrogen species, such as nitric oxide (NO)(1, 4, 5, 7). Antioxidant enzymes mainly composed of superoxide dismutase (SOD), catalase, selenium-containing glutathione peroxidase become insufficient against oxidative stress burden (4). OS begets activation of inflammatory mediators and triggers oxidation and modification of nucleic acids, proteins, lipids, carbohydrates hence leading to lipid peroxidation and the accumulation of advanced glycation end products (AGEs) which cause tissue damage in CKD. Also, hemodialysis itself is defined with increased oxidative stress, resulting from antioxidant depletion during dialysis procedure and accumulation of oxidative molecules (4, 5, 7).
Enhanced OS and inflammation which causing accumulation of oxidative products such are ROS and NO are triggered by hemodialysis are major contributors for development of endothelial dysfunction, vascular calcification, progression of atherosclerosis and resulting CVD. Systolic and diastolic function is worsened by ROS mediated cellular signaling and gene expression. Cardiac remodeling which features myocardial apoptosis, intramyocardial fibrosis, impaired diastolic filling, contractile dysfunction and chamber dilation are linked with oxidative stress which its processes mediated by the activation of several promitogenic kinases, transcription factors, matrix metalloproteinases and fibroblast proliferation (1).
Paraoxonases (PON) including PON1, PON2, and PON3 are potent antioxidant and anti-inflammatory enzymes (8). PON1 is an esterase/lactonase glycoprotein synthesized in the liver and found mainly in high-density lipoproteins (HDLs) at circulation which derives its name from its ability to hydrolyze paraoxon, a pesticide component (8, 9). PON-2 and PON-3 have lactonase activity but no paraoxonase or arylesterase activity. PON1 has wide range of abilities encompassing to hydrolyze arylesterases such as, phenyl acetates and hydrolyze lactones such as homocysteine thiolactone which is a component of atherosclerosis pathogenesis (1, 9). PON1 plays an important role at anti oxidative activity of HDL (10). HDL contains PON1 in addition to its protein and lipid components (11). Degradation of hydrogen peroxide and lipid peroxides, prevention of lipoprotein oxidation, reverse cholesterol transport which includes efflux of cholesterol from macrophages, prevention of foam cell formation is some of the effects which PON1 linked with HDL (1, 5). Decrease of PON1 activity is related with atherosclerosis which can be the possible cause of CVD at HD patients (11).
Pulmonary hypertension (PH) and pulmonary fibrosis (PF) are clinically important complications of HD patients.PH and pulmonary fibrosis are reported to have high prevalence at HD patients and pathogenesis of the both have direct links to oxidative stress and inflammation (12, 13, 14).PH and PF are related with worse outcomes and independently associated with increased CVD risk at HD patients (15). Importance of early and correct diagnosis of PH and PF is essential because of its tendency to asymptomatic course until end stage and HD patients commonly have edema and dyspnea related to volume overload which makes PH diagnosis difficult (14). Accumulation of OS products, ROS activation, endothelial dysfunction, NO decrease, increase at the levels of fibrin storages and endothelin, hemodynamic effects of the arteriovenous fistula and grafts, neutrophil activation related to dialysis membrane, pulmonary vascular calcification and extensive growth of endothelial cells are among the causes for PH. Increase of growth factors such as TGF beta, PDGF, FGF, pulmonary angiotensin converting enzyme activation, cytokine activation together with pulmonary circulation impairment and chronic volume overload helps to smooth muscle cell proliferation and pulmonary fibrosis at hemodialysis patients (12, 13, 16). Gold standard for PH diagnosis is right heart catheterization which is poorly accessible and invasive procedure (17). Pulmonary pulse transit time (pPTT) is a noninvasive method which is a valuable parameter for determining PH and PF (18).
At this study we aimed to determine relationship between PON1 activity and echocardiography parameters early diastolic mitral annular velocity (E′), pulmonary artery pressure (PAP), tricuspid annular peak systolic excursion (TAPSE), myocardial performance index (MPI), ratio of peak velocity blood flow from left ventricular relaxation in early diastole (the E wave) to peak velocity flow in late diastole caused by atrial contraction (the A wave) (E/A ratio), posterior wall thickness (PWT), interventricular septum thickness (IVS), left atrium diameter (LA), ejection fraction (EF) and pulmonary pulse transit time before and after HD session at ESRD patients. We investigated relation between PON1 and echocardiography parameters for pulmonary fibrosis parameters.