neurotoxicity and mechanisms of induced hyperexcitability

INTRODUCTIONCardiovascular diseases present a leading cause ofdeath in patients treated with haemodialysis [1, 2]. Therate of cardiovascular mortality in this population is approximately9% on an annual basis, with left ventricularhypertrophy, ischemic heart diseases and heart failure havingthe highest rates of mortality [1, 2].METHODSFor this study, the Medline database was used. The followingkey words were used for searching: risk factors, leftventricular hypertrophy, echocardiography, and haemodialysis.About 40.000 references were found dealing withthese types of problems. Systematic review articles andwell-controlled clinical studies were singled out. Editor’sletters and uncontrolled clinical studies were not used.Systematic review articles were used and analysed by theNational Kidney Foundation Kidney Disease OutcomeQuality Initiative (NKF KDOQI), which confirmed the validityand quality of the selected references.RE SULTSAetiopathogenesis of left ventricle hypertrophyThe most important risk factors of left ventricle hypertrophyin haemodialysis patients are hypertension, arteriosclerosis,adult aortic stenosis, anaemia, increased blood flowthrough the vascular access for haemodialysis and increasedvolume of extracellular fluid [3, 4]. Pressure overloads of theleft ventricle due to hypertension, aortic stenosis and arteriosclerosisof blood vessels can cause thickening of theleft ventricle wall without the enlargement of the ventriclediameter (concentric left ventricle hypertrophy) [5, 6]. Volumeoverloads of the left ventricle due to increased sodiumand water intake, anaemia and increased blood flow throughthe vascular access for haemodialysis (Q AV≥ 1000 ml/min)cause the ventricle wall to become thickened and cause anenlargement of ventricle diameter (eccentric left ventriclehypertrophy) [5, 6]. The development of left ventricle hypertrophyand fibrosis of the myocardial interstitium can alsobe affected by factors that do not depend on the afterloadand preload, such as microinflammation, oxidative stress,the activation of the intracardial renin-angiotensin system-RAS, the vitamin D deficiency and uncontrolled secondaryhyperparathyroidism, scheme 1 [7-10]. Left ventricle hypertrophygoes through two phases. Adaptive hypertrophy isactually the response to increased tension stress to the leftventricle wall and has a protective function. When volumeand pressure overload the left ventricle to the point of cardiacmuscle failure, adaptive hypertrophy becomes maladaptiveleft ventricle hypertrophy, with myocyte loss, heartfailure and, eventually, death [11].Diagnostics of left ventricular hypertrophyMorphological and functional disorders of the leftventricle in haemodialysis patients include systolic disorder,concentric hypertrophy, eccentric hypertrophy, leftventricle dilation and diastolic dysfunction. The systolicfunction of the left ventricle is disturbed when echocardiographyreveals that the fractional shortening of the leftventricle (FSLV) is ≤ 25% and that the ejection fractionof the left ventricle (EFLV) is ≤ 50% [12-14]. Concentrichypertrophy of the left ventricle is defined by a left ventriclemass index– (LVMi) > 131 g/m 2 in males and >100g/m 2 in females and a relative wall thickness of the leftventricle (RWT) > 45% [12-14]. Eccentric hypertrophy ofthe left ventricle is characterised by an increased left ventriclemass index (LVMi > 131 g/m 2 in males and >100 g/m 2 in females) and an RWT ≤ 45% [12-14]. An echochardiographicestimation of the left ventricle function in diastoleis based upon the measurement of the velocity ofearly (E) and late (A) components of blood flow throughthe mitral valve and their relative ratio E/A. There arethree types of left ventricle diastolic dysfunction: relaxationdisorder [VmaxE/VmaxA < 1,0; E wave decelerationtime (DT E) > 250 ms; and isovolumetric relaxation of theleft ventricle (IVRT) > 100 ms]; pseudonormalisation andrestriction disturbance [VmaxE/VmaxA > 1,6; DT E< 150ms; and IVRT < 60 ms] [15]. Cardiac Magnetic ResonanceImaging (CMRI) is the golden standard for remodellingof the left ventricle and for the estimation of myocardialinterstitium fibrosis in haemodialysis patients [16].Clinical importance of left ventricular hypertrophyLeft ventricle hypertrophy is accompanied by disordereddiastolic function (50-60% of haemodialysis patients), byventricle arrhythmias (dispersion interval (QTd) > 50 ms),by de novo ischemic heart disease (in patients with LVMi >160 g/m 2 ) and by unfavourable outcomes in haemodialysispatients [17-19]. A high left ventricle mass index (LVMi >120 g/m 2 ) and an LV mass/volume ratio (LVMi/iEDV) > 2,2g/ml are predictors of a poor outcome in dialysis patientswith a normal LV volume (iEDV ≤ 90 ml/m 2 ) and a normalsystolic function (FS > 25%, EF > 50%) [20, 21].Therapy of left ventricular hypertrophyWell-timed risk factor detection and adequate therapyhelp regression of left ventricle hypertrophy in haemodialysispatients [22-25]. Results of large, well-controlled clinicaltrials stress that the management of anaemia and bloodpressure control, the correction of metabolic disorders ofcalcium, phosphate, vitamin D and parathormone (parathyroidhormone), as well as the individualisation of treatmentof haemodialysis as the most important factors in the successfulmanagement of left ventricle hypertrophy [22-25].Anaemia is an important cause of left ventricle hypertrophy,and a decrease in haemoglobin of 10 g/l is38