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Aims Patients on chronic haemodialysis have a wide range of changes in cardiac function and structure, including left ventricular hypertrophy, dilation and diastolic dysfunction or pulmonary hypertension. All these changes were linked to increased mortality in previous studies. High-flow arteriovenous fistulas (AVF) are supposed to be a factor contributing to their development. This study investigated the early effect of surgical AVF blood flow (Qa) reduction on these changes in patients with or without heart failure changes. Methods and results Forty-two patients in chronic haemodialysis programme with high-flow AVF (Qa over 1500 mL/min), indicated for surgery for ≥1 of the following indications: 1.manifest heart failure; 2.hand ischemia; 3.advanced structural heart changes detected by echocardiography. The patients underwent echocardiography on selection visit, before blood flow reducing surgery and six weeks thereafter. The Qa reduction led to decrease of left ventricular mass (p = 0.02), end-diastolic volume (p = 0.008), end-diastolic diameter (p = 0.003) and left atrial volume (p = 0.0006). Diastolic function improved. Similarly, right ventricular diameter and right atrial volume decreased (p = 0.000001 and 0.00009, respectively) together with the decrease of estimated pulmonary artery systolic pressure. 81% of patients suffered from pulmonary hypertension prior to surgery, only 36% thereafter. Conclusion The surgical restriction of the hyperkinetic circulation leads to several improvements of heart structure and function, which was linked to higher mortality in other studies. The beneficial effect of Qa reduction is present even in patients without symptoms of heart failure. The contribution of AVF must be considered with structural or functional heart changes.

Background: Decreased cerebral perfusion and oxygenation are common in hemodialysis patients. Magnitude of the arteriovenous fistula involvement in this phenomenon is not known. The aim of this study was to investigate the effect that a short-term arteriovenous fistula flow interruption has on cerebral oxygenation and to review and suggest possible explanations. Methods: In 19 patients, basic laboratory and clinical data were obtained and arteriovenous fistula flow volume was measured by ultrasonography. Baseline regional cerebral oxygen saturation (rSO2) was measured by near-infrared spectroscopy. Manual pressure was then applied on the fistula, resulting in total blood flow interruption. After 1 min of manual compression, rSO2 and blood pressure values were noted again. The compression-related change in rSO2 was assessed, as well as its association with arteriovenous fistula flow volume, blood pressure, and other parameters. Results: Mean cerebral rSO2 increased after arteriovenous fistula compression (from 53.6% ± 11.4% to 55.6% ± 10.8%; p = 0.000001; 95% confidence interval = 1.39–2.56). The rSO2 increase was higher in patients with lower rSO2 at baseline (r = −0.46; p = 0.045). Conclusion: A significant rise in cerebral oxygenation was observed following the manual compression of arteriovenous fistula. Therefore, the arteriovenous fistula could have a role in impaired cerebral oxygenation in hemodialysis patients.

Chronic kidney disease (CKD) leads to profound metabolic and hemodynamic changes, which damage other organs, such as heart and brain. The brain abnormalities and cognitive deficit progress with the severity of the CKD and are mostly expressed among hemodialysis patients. They have great socio-economic impact. In this review, we present the current knowledge of involved mechanisms.

Brain tissue oxygenation (rSO2) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p˂0.001) and higher BNP level (r=-0.45, p=0.01). The rSO2 value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO2 values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO2 in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.

Background/Aims: High rates of cognitive impairment (CI) are an alarming problem in patients undergoing chronic hemodialysis (HD). Its pathophysiology remains unclear and there are indications that brain ischemia might be one of the key causes. Cerebral tissue oxygenation, as measured by near-infrared spectroscopy, is known to be decreased in HD patients. However, it is unknown whether CI is associated or not associated with lower cerebral oxygenation in these patients. The primary aim of our study was to probe this possible association. Our secondary aim was to assess other factors possibly related to cerebral ischemia and CI. Methods: Thirty-nine patients treated by chronic HD were included in this cross-sectional study. All measurements were performed before the initiation of an HD session. The Montreal Cognitive Assessment (MoCA) was administered according to published recommendations. Regional saturation of oxygen (rSO2) of the left frontal lobe was measured using the INVOS 5100C device. Basic medical history and laboratory data were recorded, and handgrip strength was analyzed. We used the unpaired t test to compare the rSO2 and other variables between cognitively normal patients (MoCA score ≥26) and those who displayed CI (MoCA score Results: Cognitively impaired patients had lower brain rSO2 values compared to cognitively normal patients (48 ± 9 vs. 57 ± 10%, p = 0.01). Among other variables, higher red cell distribution width (15.8 ± 1.9 vs. 13.8 ± 1.6%, p = 0.01) and lower hand grip strength (49.2 ± 23.3 vs. 99.3 ± 31.4 lbs, p < 0.001) also displayed a significant association with CI. The relation between rSO2 and MoCA score was significant after adjustment for age and gender (p = 0.007). Conclusion: Decreased brain oxygenation is associated with weaker cognitive performance in patients undergoing chronic HD. Further understanding the causes of cerebral ischemia in HD patients could lead to the prevention of cognitive decline in this population.

Funding Acknowledgements Grant of the Grant Agency of Charles University and grant of the Czech Health Research council Introduction Over 50% of patients treated by chronic haemodialysis programme die of cardiovascular diseases. Changes of heart structure and function can be detected by echocardiography. The most frequent changes are left ventricle hypertrophy (LVH) and its diastolic dysfunction. One of the considered contributing mechanisms is the hyperkinetic circulation. Purpose The aim of this study was to analyse the effect of high flow arteriovenous fistula (AVF) on eft ventricular hypertrophy and diastolic function. Materials and methods We included 30 patients with a high-flow arteriovenous fistula into the study, indicated for AVF blood flow reduction because of heart failure or hand ischemia. All the patients underwent echocardiographic examination and ultrasonographic measurement of AVF blood flow before and 6 weeks after the surgery. Results The AVF banding led to significant reduction of Qa (from 2977 ± 1408 to 1295 ± 610 mL/min; p ˂ 10-6, accompanied by significant decrease of cardiac index (from 4.34 ± 1.09 to 3.56 ± 0.90 L/min.m2). These findings were accompanied by significant reduction of left ventricle mass index (from 125 ± 31 to 116 ± 32 g/m2; p = 0.04) and by improvement of diastolic dysfunction grade (from 1.66 ± 0.67 to 1.14 ± 0.95; p = 0.03). The maximum velocity of tricuspid regurgitation decreased (from 3.1 ± 0.4 to 2.7 ± 0.5), and so did the left atrium volume index (from 47 ± 14 to 42 ± 15 mL/m2; p = 0.01). Conclusions LVH and diastolic dysfunction are frequent in haemodialysis patients; hyperkinetic circulation caused by high-flow arteriovenous fistula is one of the significant contributing mechanisms. Surgical reduction of AVF blood flow improved diastolic function of the left ventricle and reduced the hypertrophy in our patient population. AVF flow volume should be always considered during cardiological examination of haemodialysis patients.

The prevalence of the left ventricular hypertrophy (LVH) is very high in end-stage renal disease treated by hemodialysis. Diastolic dysfunction is a frequent consequence and leads to the development of heart failure with preserved ejection fraction. New American/European echocardiographic guidelines for the assessment of diastolic function simplified the evaluation and were published recently. The aim of this study was to reveal if the new guidelines stratify asymptomatic hemodialysis patients by the levels of brain-natriuretic peptide (BNP). A cohort of 46 patients hemodialyzed in one center with the lack of overt heart failure, systolic dysfunction, arrhythmia or significant valvular disease were examined by echocardiography before and after a single hemodialysis and blood samples for BNP analysis were drawn at both occasions. The LVH was present in 53% of patients, concentric remodeling in another 17%. Higher indexed left ventricular mass was related to higher BNP levels (r = 0.58, p = 0.0001). Before hemodialysis, diastolic dysfunction was present in 61%: grade 1 in 25%, grade 2 in 21% and grade 3 in 8%. The higher grade of diastolic dysfunction was associated with the incremental increase of BNP. The post-dialysis echocardiography did not allow the assessment of diastolic function in as many as 37% of patients. Our study has shown that the application of the current guidelines for the assessment of diastolic function based on simple four criteria differentiate hemodialysis symptomless patients with preserved systolic function according to BNP levels. BNP levels also rose together with the left ventricular mass. The ratio E/eʹ medial seemed to be a better predictor of increased BNP than E/eʹ lateral or E/eʹ averaged.

Background: Creation of vascular access leads to considerable local haemodynamic changes with decreased hand perfusion. Distal limb tissues then represent a model of hand ischaemia effect on muscles. The aim of our study was to investigate how the presence of vascular access influences the hand muscle strength in end-stage renal disease patients. Methods: We included 52 chronically haemodialysed patients with upper limb access without clinical signs of hand ischaemia. Muscle strength was evaluated by dynamometry. Finger pressure was measured on the second and fourth fingers and averaged for further analysis. Thenar tissue oxygenation (rSO2) was analysed using near-infrared spectroscopy. All examinations were performed in both the hands. Basic laboratory analysis was added. Data were processed with unpaired t-test and correlation analysis. Results: Hands with dialysis access had lower values of handgrip strength (54.2 ± 29.1 lbs vs 48.6 ± 23.4 lbs, p = 0.0006), systolic finger pressure (127.1 ± 32.0 mmHg vs 101.4 ± 31.6 mmHg, p < 10−8) and of thenar rSO2 (45.8% ± 12.9% vs 42.5% ± 13.3%, p = 0.002). Muscle strength (handgrip) was directly related to the thenar oxygenation ( r = 0.36; p = 0.014) and to the finger systolic pressure ( r = 0.38; p = 0.007) on the access extremity. On the extremity without dialysis access, handgrip strength was inversely related to patient’s age ( r = −0.41, p = 0.003), dialysis vintage ( r = −0.32, p = 0.02) and red cell distribution width ( r = −0.37, p = 0.01). Conclusion: The presence of dialysis access leads to the decrease of finger pressure, oxygenation, and also muscle strength even in the absence of clinically overt hand ischaemia. All these parameters are interrelated. This study underlines the consequences of inadequate muscle perfusion.

Tumor suppressor protein p53 possesses two DNA-binding sites. One that is located within its core domain is responsible for sequence-specific DNA binding of the protein, non-specific binding to internal segments of single- or double-stranded DNA, and to certain kinds of non-B DNA structures. The other that is contained in the C-terminus of the protein binds to damaged DNA. Binding of active, latent, and in vitro-activated p53 protein to DNA fragments modified by antitumor cisplatin was studied using electrophoretic mobility shift assay in agarose gels and immunoblotting analysis. We found that both latent and active p53 forms bound to random sequences of DNA globally modified by cisplatin with a higher affinity than to unmodified DNA. Interestingly, the latent form exhibited a more pronounced selectivity for platinated DNA than the active p53. Consistently with this observation, the preference of the latent form for platinated DNA decreased as a consequence of the activation of latent p53 by phosphorylation at the protein kinase C site within its C-terminus or by binding of the monoclonal antibody Bp53-10.1. Competition experiments involving a 20-bp consensus sequence of p53 suggested that the p53 core domain was a primary binding site of the active p53 when it bound to DNA fragments lacking consensus sequence, but modified by cisplatin. In addition, the latent protein was found to selectively interact with DNA modified by cisplatin probably via its C-terminus.