Solmaz Assa

Hemodialysis-Induced Regional Left Ventricular Systolic Dysfunction: Prevalence, Patient and Dialysis Treatment-Related Factors, and Prognostic Significance

BACKGROUND AND OBJECTIVES The hemodialysis procedure may acutely induce regional left ventricular systolic dysfunction. This study evaluated the prevalence, time course, and associated patient- and dialysis-related factors of this entity and its association with outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Hemodialysis patients (105) on a three times per week dialysis schedule were studied between March of 2009 and March of 2010. Echocardiography was performed before dialysis, at 60 and 180 minutes intradialysis, and at 30 minutes postdialysis. Hemodialysis-induced regional left ventricular systolic dysfunction was defined as an increase in wall motion score in more than or equal to two segments. RESULTS Hemodialysis-induced regional left ventricular systolic dysfunction occurred in 29 (27%) patients; 17 patients developed regional left ventricular systolic dysfunction 60 minutes after onset of dialysis. Patients with hemodialysis-induced left ventricular systolic dysfunction were more often male, had higher left ventricular mass index, and had worse predialysis left ventricular systolic function (left ventricular ejection fraction). The course of blood volume, BP, heart rate, electrolytes, and acid-base parameters during dialysis did not differ significantly between the two groups. Patients with hemodialysis-induced regional left ventricular systolic dysfunction had a significantly higher mortality after correction for age, sex, dialysis vintage, diabetes, cardiovascular history, ultrafiltration volume, left ventricular mass index, and predialysis wall motion score index. CONCLUSIONS Hemodialysis induces regional wall motion abnormalities in a significant proportion of patients, and these changes are independently associated with increased mortality. Hemodialysis-induced regional left ventricular systolic dysfunction occurs early during hemodialysis and is not related to changes in blood volume, electrolytes, and acid-base parameters.

Renal handling of galectin-3 in the general population, chronic heart failure, and hemodialysis.

Background Galectin‐3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin‐3 levels. We aimed to describe galectin‐3 renal handling in HF. Methods and Results In Sprague–Dawley rats, we infused galectin‐3 and studied distribution and renal clearance. Furthermore, galectin‐3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin‐3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin‐3. Plasma galectin‐3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P<0.001), while urinary galectin‐3 in HF patients was comparable (28.1 ng/mL versus 35.1 ng/mL, P=0.830). The calculated galectin‐3 excretion rate was lower in HF patient (2.3 mL/min [1.5 to 3.4] versus 3.9 mL/min [2.3 to 6.4] in control subjects; P=0.005). This corresponded with a significantly lower fractional excretion of galectin‐3 in HF patients (2.4% [1.7 to 3.7] versus 3.0% [1.9 to 5.5]; P=0.018). These differences, however, were no longer significant after correction for age, gender, diabetes, and smoking. HF patients who received diuretics (49%) showed significantly higher aldosterone and galectin‐3 levels. Hemodialysis patients (n=105; mean age 63 years; 65% male), without urinary galectin‐3 excretion, had strongly increased median plasma galectin‐3 levels (70.6 ng/mL). Conclusions In this small cross‐sectional study, we report that urine levels of galectin‐3 are not increased in HF patients, despite substantially increased plasma galectin‐3 levels. The impaired renal handling of galectin‐3 in patients with HF may explain the described relation between renal function and galectin‐3 and may account for the elevated plasma galectin‐3 in HF.

Strong predictive value of mannose-binding lectin levels for cardiovascular risk of hemodialysis patients

Background Hemodialysis patients have higher rates of cardiovascular morbidity and mortality compared to the general population. Mannose-binding lectin (MBL) plays an important role in the development of cardiovascular disease. In addition, hemodialysis alters MBL concentration and functional activity. The present study determines the predictive value of MBL levels for future cardiac events (C-event), cardiovascular events (CV-event) and all-cause mortality in HD patients. Methods We conducted a prospective study of 107 patients on maintenance hemodialysis. Plasma MBL, properdin, C3d and sC5b-9 was measured before and after one dialysis session. The association with future C-events, CV-events, and all-cause mortality was evaluated using Cox regression models. Results During median follow-up of 27 months, 36 participants developed 21 C-events and 36 CV-events, whereas 37 patients died. The incidence of C-events and CV-events was significantly higher in patients with low MBL levels (<319 ng/mL, lower quartile). In fully adjusted models, low MBL level was independently associated with increased CV-events (hazard ratio 3.98; 95 % CI 1.88–8.24; P < 0.001) and C-events (hazard ratio 3.96; 95 % CI 1.49–10.54; P = 0.006). No association was found between low MBL levels and all-cause mortality. Furthermore, MBL substantially improved risk prediction for CV-events beyond currently used clinical markers. Conclusions Low MBL levels are associated with a higher risk for future C-events and CV-events. Therefore, MBL levels may help to identify hemodialysis patients who are at risk to develop cardiovascular disease. Electronic supplementary material The online version of this article (doi:10.1186/s12967-016-0995-5) contains supplementary material, which is available to authorized users.

Changes in Plasma Copeptin Levels during Hemodialysis: Are the Physiological Stimuli Active in Hemodialysis Patients?

Objectives Plasma levels of copeptin, a surrogate marker for the vasoconstrictor hormone arginine vasopressin (AVP), are increased in hemodialysis patients. Presently, it is unknown what drives copeptin levels in hemodialysis patients. We investigated whether the established physiological stimuli for copeptin release, i.e. plasma osmolality, blood volume and mean arterial pressure (MAP), are operational in hemodialysis patients. Methods One hundred and eight prevalent, stable hemodialysis patients on a thrice-weekly dialysis schedule were studied during hemodialysis with constant ultrafiltration rate and dialysate conductivity in this observational study. Plasma levels of copeptin, sodium, MAP, and blood volume were measured before, during and after hemodialysis. Multivariate analysis was used to determine the association between copeptin (dependent variable) and the physiological stimuli plasma sodium, MAP, excess weight as well as NT-pro-BNP immediately prior to dialysis and between copeptin and changes of plasma sodium, MAP and blood volume with correction for age, sex and diabetes during dialysis treatment. Results Patients were 63±15.6 years old and 65% were male. Median dialysis vintage was 1.6 years (IQR 0.7–4.0). Twenty-three percent of the patients had diabetes and 82% had hypertension. Median predialysis copeptin levels were 141.5 pmol/L (IQR 91.0–244.8 pmol/L). Neither predialysis plasma sodium levels, nor NT-proBNP levels, nor MAP were associated with predialysis copeptin levels. During hemodialysis, copeptin levels rose significantly (p<0.01) to 163.0 pmol/L (96.0–296.0 pmol/L). Decreases in blood volume and MAP were associated with increases in copeptin levels during dialysis, whereas there was no significant association between the change in plasma sodium levels and the change in copeptin levels. Conclusions Plasma copeptin levels are elevated predialysis and increase further during hemodialysis. Volume stimuli, i.e. decreases in MAP and blood volume, rather than osmotic stimuli, are associated with change in copeptin levels during hemodialysis.

Comparison of Cardiac Positron Emission Tomography Perfusion Defects During Stress Induced by Hemodialysis Versus Adenosine

The cardiac stress imposed by hemodialysis may differ from that induced by pharmacologic agents used for myocardial perfusion imaging-based stress testing. With repetitive intradialytic [(13)N]ammonia positron emission tomography, we showed that standard hemodialysis had an acute adverse effect on cardiac perfusion and left ventricular function that was not detected by standard diagnostic adenosine stress testing.

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients

Background: Hemodialysis (HD) is a life-saving treatment for patients with end stage renal disease. However, HD patients have markedly increased rates of cardiovascular morbidity and mortality. Previously, a link between the complement system and cardiovascular events (CV-events) has been reported. In HD, systemic complement activation occurs due to blood-to-membrane interaction. We hypothesize that HD-induced complement activation together with inflammation and thrombosis are involved in the development of CV-events in these patients. Methods: HD patients were followed for the occurrence of CV-events during a maximum follow-up of 45 months. Plasma samples were collected from 55 patients at different time points during one HD session prior to follow-up. Plasma levels of mannose-binding lectin, properdin and C3d/C3 ratios were assessed by ELISA. In addition, levels of von Willebrand factor, TNF-α and IL-6/IL-10 ratios were determined. An ex-vivo model of HD was used to assess the effect of complement inhibition. Results: During median follow-up of 32 months, 17 participants developed CV-events. In the CV-event group, the C3d/C3-ratio sharply increased 30 min after the start of the HD session, while in the event-free group the ratio did not increase. In accordance, HD patients that developed a CV-event also had a sustained higher IL-6/IL-10-ratio during the first 60 min of the HD session, followed by a greater rise in TNF-α levels and von Willebrand factor at the end of the session. In the ex-vivo HD model, we found that complement activation contributed to the induction of TNF-α levels, IL-6/IL-10-ratio and levels of von Willebrand factor. Conclusions: In conclusion, these findings suggest that early intradialytic complement activation predominantly occurred in HD patients who develop a CV-event during follow-up. In addition, in these patients complement activation was accompanied by a pro-inflammatory and pro-thrombotic response. Experimental complement inhibition revealed that this reaction is secondary to complement activation. Therefore, our data suggests that HD-induced complement, inflammation and coagulation are involved in the increased CV risk of HD patients.

Effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and left ventricular function assessed with 13N-NH3 PET and echocardiography.

Hemodialysis is associated with a fall in myocardial perfusion and may induce regional left ventricular (LV) systolic dysfunction. The pathophysiology of this entity is incompletely understood, and the contribution of ultrafiltration and diffusive dialysis has not been studied. We investigated the effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and LV function. Eight patients (7 male, aged 55 ± 18 yr) underwent 60 min of isolated ultrafiltration and 60 min of isovolemic dialysis in randomized order. Myocardial perfusion was assessed by 13N-NH3 positron emission tomography before and at the end of treatment. LV systolic function was assessed by echocardiography. Regional LV systolic dysfunction was defined as an increase in wall motion score in ≥2 segments. Isolated ultrafiltration (ultrafiltration rate 13.6 ± 3.9 ml·kg-1·h-1) induced hypovolemia, whereas isovolemic dialysis did not (blood volume change -6.4 ± 2.2 vs. +1.3 ± 3.6%). Courses of blood pressure, heart rate, and tympanic temperature were comparable for both treatments. Global and regional myocardial perfusion did not change significantly during either isolated ultrafiltration or isovolemic dialysis and did not differ between treatments. LV ejection fraction and the wall motion score index did not change significantly during either treatment. Regional LV systolic dysfunction developed in one patient during isolated ultrafiltration and in three patients during isovolemic dialysis. In conclusion, global and regional myocardial perfusion was not compromised by 60 min of isolated ultrafiltration or isovolemic dialysis. Regional LV systolic dysfunction developed during isolated ultrafiltration and isovolemic dialysis, suggesting that, besides hypovolemia, dialysis-associated factors may be involved in the pathogenesis of hemodialysis-induced regional LV dysfunction.

AGES IN HEMODIALYSIS: TISSUE- AND PLASMA- AUTOFLUORESCENCE

Evaluation of air contamination incidences and in vitro settings and experiences of micro bubblesThe use of citrate-containing dialysate for anticoagulation in hemodialysis (hd). report of clinical experienceK1 (EI0154) AGES IN HEMODIALYSIS: TISSUEAND PLASMAAUTOFLUORESCENCE R. Graaff1, S. Arsov1, L. Trajceska4, P. Dzekova4, G.E. Engels1, M. Koetsier1, W. van Oeveren1, L Lundberg5, S. Assa2, C.F.M. Franssen2, A.J. Smit3, G. Rakhorst1, A. Sikole2, B. Stegmayr5 1Dept. of Biomedical Engineering, 2Internal Medicine, Div. Nephrology and 3Div. Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands; 4Department of Nephrology, University Clinic of Nephrology, Skopje, R. Macedonia; 5Department of Internal Medicine, University Hospital, Umea, SwedenObjectives: During HD previous studies have shown that especially micro bubbles of air may pass the air detector. These studies focused to analyse in vitro if the air trap of various producers may ...Artificial Kidney – Uremic Toxins – SYMPOSIUM, 606 Smart and Responsive Biomaterials – SYMPOSIUM, 607 Cardiovascular General 1: Devices – GENERAL SESSION, 608 Ambulatory Blood Processing – SYMPOSIUM, 610 Animal Models for Tissue Engineering – SYMPOSIUM, 610 Cardiovascular General 2: Devices Interaction – GENERAL SESSION, 612 Artificial Muscle for Internal Organ – SYMPOSIUM, 613 Functionalized Biomaterials – SYMPOSIUM, 614 Cardiovascular General 3: Physiology and Pump Control – GENERAL SESSION, 615 Vascular Access in Hemodialysis – SYMPOSIUM, 617 Polymeric Membranes/Blood Interfaces – SYMPOSIUM, 618 Nano and Micro Technology: Driving the Future of Organ Recovery & Development – SYMPOSIUM, 619 Roadbumps for Tissue-Engineering Artificial Organs – SYMPOSIUM, 621 Artificial Liver GENERAL SESSION, 621 Tissue Engineering Approaches – SYMPOSIUM, 622 Cardiovascular General 4: Cardiopulmonary – GENERAL SESSION, 624 Artificial Kidney Dialysis – SYMPOSIUM, 625 Tissue Engineering of Skin: Creating a New Bio-Artificial Organ for Clinical Application – SYMPOSIUM, 627 Cardiovascular General 5: Device & Biology – GENERAL SESSION, 628 Citrate Anticoagulation A Future Option for Extracorporeal Blood Purification – SYMPOSIUM, 629 Latest Advances in Preventive and Regenerative Medicine Technologies – SYMPOSIUM, 630 Intra-Aortic Balloon Pump as a Cardiac Assist Device – SYMPOSIUM, 631 Artificial Organ Transplantation – SYMPOSIUM, 632 New Biomaterials and Scaffolds – SYMPOSIUM, 633 Modelling of Cardiovascular and Pulmonary Function in Regard to Clinical Applications – SYMPOSIUM, 634 Artificial Kidney Dialysis Techniques – SYMPOSIUM, 635 Natural Based Polymeric Biomaterials and Composites for Regenerative Medicine – SYMPOSIUM, 637 Partial Cardiac Support in Shortand Long-Term Application – SYMPOSIUM, 638 Artificial Organs – Practical Applications – GENERAL SESSION, 639 Non-Destructive Techniques to Monitor 3D In Vitro Tissue Engineering Constructs – SYMPOSIUM, 640 Stent and Vascular Prosthesis – GENERAL SESSION, 641 Dialysis Techniques Access – GENERAL SESSION, 643 Scaffolds for TE Via Electrospinning-Structures and Biomaterials – SYMPOSIUM, 644 Drug Delivery Systems – GENERAL SESSION, 646 “Approval Procedures for Medical Devices: Facts, Figures and Basic Rules Seen from Different Continental Perspectives – Artificial Organs and Society: Recent Trends in Japan”, 647K1 (EI0154) AGES IN HEMODIALYSIS: TISSUEAND PLASMAAUTOFLUORESCENCE R. Graaff1, S. Arsov1, L. Trajceska4, P. Dzekova4, G.E. Engels1, M. Koetsier1, W. van Oeveren1, L Lundberg5, S. Assa2, C.F.M. Franssen2, A.J. Smit3, G. Rakhorst1, A. Sikole2, B. Stegmayr5 1Dept. of Biomedical Engineering, 2Internal Medicine, Div. Nephrology and 3Div. Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands; 4Department of Nephrology, University Clinic of Nephrology, Skopje, R. Macedonia; 5Department of Internal Medicine, University Hospital, Umeå, SwedenDoes the advanced glycation end-products (ages) food intake influence mortality in dialysis patients?