Blood Volume Research Articles

Tolvaptan therapy for edema in patients with chronic kidney disease.

Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p<0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.

Hardware and software co-design for detecting hypertension from photoplethysmogram

Hypertension is one of the leading causes of cardiovascular disease morbidity in the world. If remains untreated, it may cause severe damage like heart attack or even death. Early detection is required to prevent the development of other cardiac abnormalities. Photoplethysmogram (PPG) is a bio signal that can be obtained optically by a sensor. It is studied to monitor the change of volume of blood and detect heart conditions. Previous studies have already applied PPG to detect hypertension at the software level. In this article, along with software-based detection, we have implemented a digital hardware-based system for detecting hypertension from signals recorded using PPG sensor. Xilinx ZedBoard Zynq-7000 field programmable gate array (FPGA) board is utilized for designing the embedded system. The hypertension detection accuracy is 98.02% at the software level while for the digital system, it is 96.05% consuming 0.374 W power. The study can be analyzed for other cardiac disease detection and medical equipment development.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded. Participants were split into a predisposed HFpEF group, defined as HFpEF with normal natriuretic peptide levels based on an HFA-PEFF (Heart Failure Association Pretest Assessment, Echocardiography and Natriuretic Peptide, Functional Testing, and Final Etiology) score of 4 from the latest European Society of Cardiology guidelines, and an HFpEF group (HFA-PEFF score of ≥ 5). An asymptomatic control group without heart failure was also included. Clinical and cardiac MRI-based characteristics and outcomes were compared between groups. The primary end points were death, heart failure hospitalization, or stroke. Results A total of 213 participants with HFpEF, 151 participants with predisposed HFpEF, and 100 participants in the control group were analyzed. Compared with the control group, participants with predisposed HFpEF had worse left ventricular remodeling and function and higher systemic inflammation. Compared with participants with HFpEF, those with predisposed HFpEF, whether obese or not, were younger and had higher plasma volume, lower prevalence of atrial fibrillation, lower left atrial volume index, and less impaired left ventricular global longitudinal strain (-12.2% ± 2.8 vs -13.9% ± 3.1; P < .001) and early-diastolic global longitudinal strain rate (eGLSR, 0.52/sec ± 0.20 vs 0.57/sec ± 0.15; P = .03) but similar prognosis. Atrial fibrillation occurrence (hazard ratio [HR] = 3.90; P = .009), hemoglobin level (HR = 0.94; P = .001), and eGLSR (per 0.2-per-second increase, HR = 0.28; P = .002) were independently associated with occurrence of primary end points in participants with predisposed HFpEF. Conclusion Participants with predisposed HFpEF showed relatively unique clinical and cardiac MRI features, warranting greater clinical attention. eGLSR should be considered as a prognostic factor in participants with predisposed HFpEF. Keywords: Heart Failure with Preserved Ejection Fraction, Normal Natriuretic Peptide Levels, Cardiovascular Magnetic Resonance, Myocardial Strain, Prognosis Clinical trial registration no. NCT04603404 Supplemental material is available for this article. © RSNA, 2024.

Assessing the clinical efficacy of low-volume therapeutic plasma exchange in achieving recovery from acute liver failure induced by yellow phosphorous poisoning.

Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen-induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV-TPE) efficacy in improving the transplant free survival in YP poisoning. Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV-TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV-TPE details were captured. The study end point was clinical outcome of the patients. Among 36 patients, 19 underwent LV-TPE and 17 opted out of LV-TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV-TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV-TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. A well-timed LV-TPE improves the survival of patients with ALF due to YP poisoning.

Prognostic impact of plasma volume status during hospital admission in patients with acute decompensated heart failure.

Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long-term mortality in patients with ADHF admitted to the CICU. Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9±12.9years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan-Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all-cause mortality during the observation period (1134days). The primary endpoint of this study was all-cause mortality. The Kaplan-Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log-rank test: P=0.016, P=0.005 and P<0.001, respectively). Univariate Cox regression analysis showed that age, body mass index, history of heart failure, use of beta-blockers, albumin level, blood urea nitrogen level, N-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction were significantly different among the PVS groups and thus were not significant prognostic factors for ADHF. Furthermore, the multivariate analysis revealed that PVS at discharge [hazard ratio (HR)=1.06 (1.00-1.12), P=0.048] was an independent poor prognostic factor for ADHF. This study highlights the effect of PVS measured at different timepoints on the prognoses of ADHF patients. Regular assessment of PVS, particularly at discharge, is crucial for optimising patient management and achieving favourable outcomes in cases of ADHF.

L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial

The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation.

Hemodynamic effects of low versus high dialysate bicarbonate concentration in hemodialysis patients.

Hemodialysis treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with hemodynamic instability. The aim of this study was to perform a detailed comparison of high and low dialysate bicarbonate in terms of blood pressure, intradialytic hemodynamic parameters, orthostatic blood pressure, and electrolytes. Fifteen hemodialysis patients were examined in a single-blind, randomized, controlled, crossover study. Participants underwent a 4-h hemodialysis session with dialysate bicarbonate concentration of 30 or 38 mmol/L with 1 week between interventions. Blood pressure was monitored throughout hemodialysis, while cardiac output, total peripheral resistance, stroke volume, and central blood volume were assessed with ultrasound dilution technique (Transonic). Orthostatic blood pressure was measured pre- and post-hemodialysis. With similar ultrafiltration (UF) volume (2.6 L), systolic blood pressure (SBP) tended to decrease more during high dialysate bicarbonate compared to low dialysate bicarbonate; the mean (95% confidence interval) between treatment differences in SBP were: 8 (-4; 20) mmHg (end of hemodialysis) and 7 (0; 15) mmHg (post-hemodialysis). Stroke volume decreased whereas total peripheral resistance increased significantly more during high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment differences: Stroke volume: 12 (1; 23) mL; Total peripheral resistance: -2.9 (-5.3; -0.5) mmHg/(L/min). Cardiac output tended to decrease more with high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment difference 0.7 (0.0; 1.4) L/min. High dialysate bicarbonate caused alkalosis, hypocalcemia, and lower plasma potassium, whereas patients remained normocalcemic with normal pH during low dialysate bicarbonate. Orthostatic blood pressure response after dialysis did not differ significantly. The use of high dialysate bicarbonate compared to low dialysate bicarbonate was associated with hypocalcemia, alkalosis, and a more pronounced hypokalemia. During hemodialysis with UF, a better preservation of blood pressure, stroke volume, and cardiac output may be achieved with low dialysate bicarbonate compared to high dialysate bicarbonate.

The Lebanese percreta group: A retrospective cohort study of both radical and conservative management outcomes of abnormally invasive placenta.

The aim of the present study was to illustrate the outcomes of abnormally invasive placenta (AIP) cases managed in three leading centers in Lebanon. We conducted a retrospective multicenter cohort study. Patients managed conservatively (cesarean delivery with successful placental separation) or radically (cesarean hysterectomy) were included in the study. Data included patient characteristics, surgical outcomes (blood loss, operative time, transfusion, partial bladder resection), maternal outcomes (death, length of stay, ICU admission, postoperative hemoglobin level) and neonatal outcomes (Apgar score, neonatal weight, admission to neonatal intensive care unit, neonatal death). The study included 189 patients. In the radical treatment subgroup (141/189), patients were para 3 and delivered at 34 4/7 weeks in average, bled 1.5 L and were transfused with three packed red blood cells, with operative time averaging 160 min. A total of 36% were admitted to the ICU and patients stayed on average for 1 week despite partial bladder resection in 19% of cases. Unscheduled radical delivery occurred at a lower gestational age, was associated with more blood loss, higher rate and volume of transfusion, and risk of maternal and neonatal death. In addition, patients delivered in an unscheduled fashion experienced higher rates of partial bladder resection and longer interventions. In the conservative treatment subgroup, on average patients were para 2 and delivered at 36 weeks, bled 800 mL on average with low rates of transfusion (35%) and ICU admission (22.9%). With regard to neonatal outcomes, the average neonatal birth weight was 2.4 kg in the radical subgroup and 2.5 kg in the conservative subgroup. Neonatal death occurred in 5.4% of cases requiring radical management while it occurred in 2% of patients treated conservatively. Through their multidisciplinary approach, the three centers demonstrated that management of AIP in Lebanon has led to excellent outcomes with no maternal mortality occurring in scheduled radical treatment. By comparison of the three leading centers, pitfalls in each center were identified and addressed.

Contrast-enhanced ultrasound features as potential biomarker for prediction of breast cancer recurrence.

Purpose To investigate the associations between contrast-enhanced ultrasound imaging features and disease recurrence among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy. Materials and Methods In the study, pre- and post-neoadjuvant chemotherapy contrast-enhanced ultrasound images of 43 patients with breast cancer were retrospectively analysed. Post-acquisition image processing involved the placement of freehand-drawn regions of interest, followed by the generation of blood flow kinetics representing blood volume and velocity for these regions of interest. Qualitative and quantitative contrast-enhanced ultrasound parameters were compared to predict recurrence, and receiver operating characteristic analysis was used to evaluate predictive ability. Results Among the 43 patients, 10 (23%) exhibited disease recurrence (median [range]: 27 [4-68] months). Post-neoadjuvant chemotherapy peak enhancement, wash-in area under the curve, wash-out area under the curve, and wash-in and wash-out area under the curve (p=0.003, p=0.004, p=0.026, and p=0.014, respectively) differed between the no-recurrence and recurrence groups. The area under the receiver operating characteristic curve (0.88; 95% confidence interval: 0.75-1.00) for post-neoadjuvant chemotherapy peak enhancement was the highest among the contrast-enhanced ultrasound parameters, with a cut-off of 13.33 arbitrary units. Conclusion Higher peak enhancement on post-neoadjuvant chemotherapy contrast-enhanced ultrasound images were associated with recurrence in women with locally advanced breast cancer and is a potential biomarker of tumour recurrence.

Primary brain lymphoma and glioblastoma: evaluation of DCE T1 and DSC T2 MRI perfusion findings.

The accurate differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma multiforme (GBM) is clinically crucial due to the different treatment strategies between them. To define magnetic resonance imaging (MRI) perfusion findings in PCNSL to make a safe distinction from GBM with dynamic contrast-enhanced (DCE) T1 and DSC T2 MRI perfusion findings. This retrospective analysis included 19 patients with histopathologically diagnosed PCNSL and 21 individuals with GBM. DCE T1 vascular permeability perfusion values including K-trans, Ve, Kep, IAUGC, and DSC T2 perfusion values including cerebral blood volume (CBV) and cerebral blood flow (CBF) in axial sections from the pathological lesion and contralateral normal brain parenchyma were measured quantitatively using region of interest analysis. The study observed no statistically significant difference between patients with PCNSL (T/B cell) and GBM in the median values of DCE T1 perfusion ratios (P > 0.05). Nevertheless, the DSC T2 perfusion ratios showed a substantial distinction between the two groups. In contrast to patients with PCNSL (1.185 vs. 1.224, respectively), those with GBM had higher median levels of r-CBV and r-CBF (2.898 vs. 2.467, respectively; P 0.01). A cutoff value of ≤1.473 for r-CBV (Lesion/N) and ≤1.6005 for r-CBF (Lesion/N) was found to estimate the positivity of PCNSL. DSC T2 MRI perfusion values showed lower r-CBV and r-CBF values in PCNSL patients compared to GBM patients. According to the findings, r-CBV and r-CBF are the most accurate MRI perfusion parameters for distinguishing between PCSNL and GBM.

E.2 Proof of concept for liquid biopsy: positive correlation between extracellular vesicles shed by high grade gliomas and volume of hypervascular tumour tissue on MRI

Background: High grade gliomas (HGGs) shed extracellular vesicles (EVs) into the bloodstream. EV-derived RNA (EV-RNA) can be detected in plasma, making it a potential biomarker for HGG recurrence after treatment. We sought to establish a baseline relationship between EV-RNA in plasma and hypervascular HGG tissue on MRI. Methods: Eight patients with a new diagnosis of HGG had measurements of plasma EV-RNA and contemporaneous dynamic susceptibility contrast (DSC) MRI. Patient-specific median signal intensity of corpus callosum (mSI-CC) was determined from 10 measurements on the relative cerebral blood volume (rCBV) map. Tumour tissue with signal intensity &gt; mSI-CC and &gt; 2x, &gt; 3x, &gt; 4x and &gt; 5x mSI-CC was segmented on the rCBV map. EV-RNA plasma concentration was correlated with tissue volumes. Results: Pearson correlation showed a significant positive relationship between EV-RNA plasma concentration and tissue volume with signal intensity &gt; mSI-CC (r(6) = 0.899, p = 0.002). No significant relationship could be detected for progressively smaller tissue volumes with signal intensity &gt; 2x, &gt; 3x, &gt; 4x and &gt; 5x mSI-CC. Conclusions: EV-RNA plasma concentration correlates strongly with the total volume of hypervascular HGG tissue on DSC MRI at baseline and merits further evaluation as a biomarker of tumour behaviour in longitudinal imaging studies.

Association between pre-treatment computed tomography findings and post-treatment persistent decrease in lung perfusion blood volume

The purpose of this study was to evaluate pre-treatment CT findings in patients with acute pulmonary embolism (PE) and determine the imaging findings associated with residual hypoperfused segments in post-treatment lung perfused blood volume (LPBV). We evaluated 91 patients with acute PE who underwent dual-energy CT before and after treatment. The location of thrombi (proximal or distal) and patency of the pulmonary artery (occlusive or non-occlusive) were recorded using pre-treatment computed tomography pulmonary angiography (CTPA). Residual hypoperfusion was defined as a perfusion-decreased area seen in both the pre- and post-treatment LPBVs. The association of the location of the thrombus and vascular patency of pre-treatment CTPA with residual hypoperfusion on a segmental and patient basis was examined. In the segment-based analysis, the proportion of residual hypoperfusion in the proximal group was significantly higher than that in the peripheral group (33/125 [26.4%] vs. 9/87 [10.3%], P = 0.004). Patient-based analysis also showed that the proportion of residual hypoperfusion in patients with pre-treatment proximal thrombus was significantly higher than those without (16/42 [38.1%] vs. 3/25 (12.0%); P = 0.022). Pre-treatment vascular patency was not significantly associated with residual hypoperfusion (P > 0.05). Therefore, careful follow-up is necessary, especially in patients with proximal thrombi.

Grading of skull base meningiomas by combined perfusion: arterial spin labeling and T2* dynamic susceptibility perfusion

BackgroundConventional MRI has no distinction between high- and low-grade meningiomas, which has a crucial for choice of therapeutic plan, especially skull base meningiomas which need more meticulous endoscopy-approached surgery. The aim of our study was to evaluate role of perfusion by arterial spin labeling and dynamic susceptibility perfusion in grading of skull base meningiomas.ResultsThe relative arterial spin labeling (ASL), tumor blood flow (TBF), and tumor blood volume (TBV) ratios showed significant differences between low- and high-grade meningiomas.ConclusionsMRI perfusion is a useful in differentiation between low- and high-grade meningiomas. There is significant correlation between ASL and DSC perfusion supporting possibility of using ASL in clinical practice as an alternative technique to DSC perfusion, particularly for patients with renal impairment where no contrast injection needed.

NT-proBNP in severe aortic valve stenosis: necessity for higher cut-off values regarding congestive heart failure detection in atrial fibrillation

Abstract Background NT-proBNP is an established biomarker for the determination of fluid overload. Patients suffering from atrial fibrillation seem to have higher serum levels of NT-proBNP than patients in sinus rhythm, independent from fluid overload. However, there is no established alternative cut-off for patients with atrial fibrillation, especially in patients with severe aortic valve stenosis. Aim The aim of the current study was to evaluate the levels of serum NT-proBNP for patients with atrial fibrillation (AF) and sinus rhythm (SR) for the determination of fluid overload in patients with severe aortic valve stenosis. Methods 167 Patient suffering from severe aortic valve stenosis undergoing evaluation for TAVR at our hospital were included in this study. Upon recruitment blood samples from every patient were collected and an ECG was documented for each patient. Serum NT-proBNP was measured and volume overload was objectivated by calculation of plasma volume status (PVS), an already published method to estimate fluid overload or depletion by using a formula including weight and haematocrit. Results 37 patients (22.2%) suffered from AF upon recruitment. 47 patients (28.1%) showed fluid overload, indicated by increased PVS (PVS &amp;gt; 0, SR n=37, AF n=10). 94 patients (56.3%) were male and mean age was 80 years. Patients with and without AF showed no significant difference in age, sex or prevalence of cardiovascular diseases, except for gradients across the aortic valve (SR 47mmHg vs. AF 38mmHg; p&amp;lt;0.05) and left ventricular ejection fractions (SR 57% vs. AF 55%; p&amp;lt;0.05). Patients suffering from atrial fibrillation showed significantly higher serum levels of NT-proBNP (4843 ng/L vs. 1226 ng/L, p&amp;lt;0.001). ROC-analyses in patients with SR and severe aortic valve stenosis, showed satisfying results for NT-proBNP (AUC 0.72; sensitivity 0.81; specificity 0.58) to detect fluid overload. Comparable results were evident in patients with AF (AUC 0.77; sensitivity 0.70; specificity 0.78), but cut-off-values in patients suffering from atrial fibrillation were more than six times as much as in patients with sinus rhythm (6575 ng/L vs. 1053 ng/L). Conclusion NT-proBNP proved itself as a sufficient marker to determine volume overload in patients with severe aortic valve stenosis. Cut-offs for accurate determination of fluid overload deviate greatly in patients with sinus rhythm and atrial fibrillation, therefore different cut-offs might be required.

#1816 CA 125 as a surrogate marker for plasma volume in patients with cardiorenal syndrome

Abstract Background and Aims Assessing volume status in heart failure (HF) and end-stage chronic kidney disease (CKD) is challenging. Plasma volume expansion is an early step in the pathophysiology of decompensated HF and an independent risk factor for death and HF hospitalization, and should be addressed early. Evaluating plasma volume, especially its variation with diuretic therapy, can be a useful clinical tool for guiding decongestive therapy. There's a growing need for accurate and simple tools to guide clinician decisions on patient volume management. Cancer antigen 125 (CA125), a glycoprotein produced in mesothelial cells in the pericardium, pleura, or peritoneum, is primarily associated with ovarian and gynecological malignancies. Recent studies link CA125 to inflammation and congestion. In acute HF, elevated CA125 is associated with fluid overload indicators like increased central venous and pulmonary wedge pressure. Elevated CA125 in acute HF patients is linked to worse outcomes in death and hospital stay length. Evidence supports CA125-guided therapy in acute HF, but its role in managing chronic volume overload is still uncertain. We aim to assess the relationship between CA125 levels and estimated plasma volume (ePV). Method A retrospective unicentric observational study was conducted between June 2022, and April 17, 2023, at the Renocardiac clinic of a tertiary hospital. Clinical data were extracted from electronic patient records. CKD staging was determined following the Kidney Disease Improving Global Outcomes (KDIGO) classification. ePV was calculated using the Kaplan-Hakim formula. CA125 and ePV were assessed for the same patient in 2 different visits and their variation was calculated. The correlation between CA125 and ePV, as well as CA125 and ePV variation, was evaluated using Spearman's rank correlation coefficient for bivariate analysis, conducted with IBM SPSS®. Results This study comprised 65 patients, totaling 124 hospital visits. The patient demographic was 67.7% male, with a mean age of 76.4 (±12.47) years. In terms of CKD staging, 48.5% were classified as KDIGO 5, 40.6% as KDIGO 4, 9.4% as KDIGO 3, and 1.5% as KDIGO 2. HF etiology distribution included 59% ischemic, 9.8% hypertensive, 6.5% valvular, and 24.5% other causes. The mean ejection fraction was 37.35 (±12.36)% and 19% had preserved ejection fraction; 75% of them were treated with prognostic-modifying medication, including SGLT2 inhibitors. This proportion was lower (19%) in patients with reduced ejection fraction, receiving ACE/angiotensin ± neprilysin inhibitor + mineralocorticoid receptor inhibitor + beta-blocker + SGLT2 inhibitor. During the follow-up period, 13 hospitalizations, 1 major adverse cardiovascular event (MACE), and 5 deaths were recorded. The mean CA125 level was 193.98 (±154.55) U/mL, and patients had a mean ePV of 2.41 (±1.19) L. A significant positive correlation was found between CA125 levels and ePV (r = 0.355, p = 0.000). However, there was no significant correlation between the variation of CA125 and ePV levels between visits (p = 0.535). Conclusion This study focuses on a population with limited implementation of disease-modifying therapy due to advanced CKD, complicating the clinical management of volume status, kidney function, potassium levels, and long-term prognosis in both CKD and HF. CA125 shows potential clinical utility as a marker of congestion, aiding clinicians in assessing volume status by correlating with plasma volume. However, this study found no correlation between CA125 variation and changes in plasma volume. The outpatient nature of the studied population, typically euvolemic, may hinder assessing the relationship between CA125 and ePV changes. Future studies with larger sample sizes are essential to clarify this relationship and potentially identify volume-expanded patients early.

#1328 Haemodynamic effects of low versus high dialysate bicarbonate concentration in haemodialysis patients

Abstract Background and Aims Haemodialysis (HD) treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with haemodynamic instability. We performed a detailed comparison of blood pressure (BP), haemodynamic parameters, electrolytes and orthostatic BP response with low (LDB) versus high dialysate bicarbonate concentration (HDB). Method Fifteen HD patients were examined in a single-blind, randomised, controlled, crossover study. Participants underwent a 4-hour HD session with dialysate bicarbonate concentration of 30 mmol/l (LDB) or 38 mmol/l (HDB) with one week between interventions. During HD, cardiac output (CO), total peripheral resistance (TPR), stroke volume (SV) and central blood volume were measured with ultrasound dilution technique (Transonic). Throughout dialysis, blood samples were obtained from the arterial cannula. Orthostatic BP was measured pre and post HD. Results With similar ultrafiltration volume (2.6 litres), systolic BP tended to decrease more during HDB compared to LDB (Fig. 1 and Table 1); the mean (95% confidence interval) between treatment differences in systolic BP were: 8 (-4;20) mmHg (end of HD) and 7 (0;15) mmHg (post HD). SV decreased (Fig. 2) whereas TPR increased significantly more during HDB compared to LDB with mean between treatment differences: SV: 12 (1;23) ml; TPR: -2.9 (-5.3;-0.5) mmHg/(L/min). CO tended to decrease more with HDB compared to LDB with mean between treatment difference 0.7 (0.0;1.4) L/min. HDB caused alkalosis, hypocalcaemia and lower plasma potassium, whereas patients remained normocalcaemic with normal pH during LDB (Table 1). Orthostatic BP response after dialysis did not differ significantly. Conclusion HDB compared to LDB was associated with hypocalcaemia and alkalosis and a more pronounced hypokalaemia which may impair preservation of BP, SV and CO during HD.

#1806 Cycling is safe – effect of intradialytic cycle ergometry on cerebral oxygenation and cognitive function – a pilot study

Abstract Background and Aims Patients on chronic hemodialysis benefit from intradialytic exercise with improvements in endurance, muscle strength and health-related quality of life. It is not known whether the increased oxygen demand during intradialytic exercise negatively affects cerebral oxygenation and cerebral function. The aim of the study was to assess the risk of cerebral undersupply by measuring cerebral oxygenation, perfusion and cognitive function during and after intradialytic ergometer training. Method Twelve patience on maintenance hemodialysis (HD) trice weekly were included in the study. In an initial ramp test, using bed cycle ergometer, we first determined the maximum physical strength (Pmax) at the level of exhaustion (HD A). Then, one hour after start of a second HD (HD B), patients performed 40%, 50% and 60% of Pmax for 6 min. Pulmonary function tests, blood volume (BVM), cardiac output (by electrical cardiometry), regional cerebral oxygen saturation (rSO2) (by near-infrared spectroscopy) and cerebral blood flow (CBF, by Doppler sonography) were measured. The relative changes in rSO2, CBF and hematocrit were used to calculate cerebral oxygen supply (DO2). Cognitive tests (Stroop, Trail Making and Mini Addenbrookes Cognitive Examination Test) were performed before and after HD sessions with and, as controls, without ergometry (HD-C). Results Median age was 68 (42-85) years, 9/12 were male, complete data set was obtained in 10 patients. During step test exercise (HD B), at the highest exercise level (according to Borg (1-10) 6.75 ± 2.9), rSO2 increased (+6 ± 9%, p=0.034) without a significant change in CBF. In the meantime, relative blood volume decreased during ergometry (-5.8 ± 2.73%; p=0.002), causing a temporary increase of hematocrit. Despite a small decrease in CBF in 3 patients, the mean change of rSO2, CBF and hematocrit always had a positive trend in all patients, as a surrogate of stable cerebral oxygen supply (Table 1). In comparative cognitive tests (B vs. C), we observed no significant changes in cognitive functions. Conclusion In this pilot study, intradialytic bed-cycle ergometry during the first hour of HD for &amp;lt;20 min at 40-60% of patients’ individual maximum intensity had no negative effects on cerebral oxygenation and function. Specific studies testing the safety intradialytic exercise with different conditions, such as increasing intensity or duration, are needed.

#500 Monitoring relative blood volume and calf bioimpedance in hemodialysis patients

Abstract Background and Aims Measurements of relative blood volume (RBV, %) are used to monitor the relative change in blood plasm during hemodialysis (HD). Continuous measurement of calf extracellular volume (cECV) during HD allows the calculation of relative change in cECV (RCE). RCE was defined as the ratio of cECV to its initial value, cECV0 (RCE = 100 × cECV/cECV0, %). The aim of our study was to investigate the relationship between RBV, RCE and the occurrence of intradialytic hypotension (IDH). Method Fifty-five HD patients were studied. We reduced the HD target weight stepwise by 0.1 to 0.2 kg per HD session until clinically defined IDH symptoms occurred. RBV was monitored using the blood volume monitor (BVM, Fresenius Medical Care, Germany). Whole body bioimpedance spectroscopy (wBIS) provided whole body ECV (wECV) and intracellular volume (wICV) pre and post HD. Continuous calf bioimpedance (Hydra 4200, Xitron Technologies, San Diego, CA USA) provided cECV during HD. Pre HD overhydration (OH) was calculated according to whole body composition model (Chamney et al, Am J Clin Nutr 2007; 85:80). Total number of HD sessions in all patients were divided into three groups according to the pre HD OH: 1) normal OH (NOH, OH &amp;lt; 1 L), 2) moderate OH (MOH, 1 ≤ OH &amp;lt; 4 L) and 3) severe OH (SOH, OH ≥ 4 L). Furthermore, patients were stratified by the presence or absence of IDH in each hydration group. Ultrafiltration rate (UFR), pre HD body weight, body mass index (BMI) were measured. Minimal RBV (RBVMin) and minimal RCE (RCEMin) in each HD session were recorded. These measures represent maximum reduction of fluid in the intravascular and interstitial spaces, respectively. Reducing cECV can be considered as refilling fluid from interstitial transferring to intravascular space driving by ultrafiltration. The difference between RCEMin and RBVMin was defined as vascular refilling capacity. Linear mixed-effect logistic regression (LMELR) analysis was applied to explore relationships between IDH with RBVMin, RCEMin, wECV and BMI. Results We studied 621 HD sessions in 55 patients. MOH was present in 57%, SOH in 22% and NOH in 21% of total number of HD sessions respectively. There were significant differences in age, UFR, RBVMin, RCEMin, pre HD wECV, BMI between three groups, while the IDH rate did not differ significantly (Table 1). RBVMin was inversely correlated with UFR (Fig. 1) in all measurements. Pre HD wECV was the only factor associated with IDH in overall measurement. Pre HD wECV was significantly lower in IDH than in non-IDH patients in the NOH group (Fig. 2). In the MOH group, UFR and RCEMin-RBVMin were higher in IDH than in non-IDH patients (Fig. 3a and Fig. 3b). In the SOH group, Pre HD OH is the major factor associated with IDH (Fig. 4). Conclusion This study found that the major factors leading to IDH are 1) lower hydration status; 2) relative higher UFR; and 3) the limited refilling capacity. RBVMin correlated with UFR, but it did not predict IDH. Combined analysis of RBV and calf bioimpedance may provide a means to quantitate the fluid transport between intravascular and interstitial compartments and could add to an early IDH warning system.

Cardiopulmonary deconditioning and plasma volume loss are not sufficient to provoke orthostatic hypertension.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

#373 Risk factors for progressive cardiorenal syndrome in patients with chronic kidney disease: the CRIC study

Abstract Background and Aims Cardiorenal syndrome (CRS) is associated with poor outcomes. However, risk factors for progressive CRS are not well studied in patients with chronic kidney disease (CKD). We studied the incidence and risk factors for progressive CRS in a cohort of CKD patients. Method 3 557 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study were included in this analysis after excluding those with heart failure (HF) at baseline visits. The mean follow-up time was 10.5 years. Progressive CRS was defined as development of both HF and renal failure (RF) (dialysis or transplant) within 12 months of each other. Cox proportional hazards models were used to examine the association of risk factors with progressive CRS. In a sensitivity analysis, risk factors for CRS type 2 (HF preceded RF during entire follow up) and CRS type 4 (RF preceded HF) were analyzed. Results The average baseline age was 59 years for those with progressive CRS and 57 years for those without. The age-adjusted incidence of progressive CRS was 4.5/1000 person-years and was 5.0/1000 person-years in Men and 5.9 in Black. The multivariable-adjusted hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for traditional risk factors are as follow: less than high school education (1.82, 1.2-2.73), history of cardiovascular disease (CVD) (1.48, 1.03-2.12), lower educational attainment (per 1 standard deviation [SD]) in eGFR (1.83, 1.40-2.39), and higher (per 1 SD) albumin-to-creatinine ratio (ACR) (2.26, 1.78-2.86). The multivariable-adjusted HRs with corresponding 95% CIs for a one-standard deviation increase in novel risk factors are as follows: hemoglobin (0.82, 0.68-0.99), hemoglobin A1C (1.31, 1.14-1.52), log alkaline phosphatase (1.18, 1.00-1.38), and log brain natriuretic peptide (1.32, 1.10-1.57), adjusting for age, sex, race, clinic sites, and all significant traditional risk factors (education, CVD, eGFR, and ACR). In sensitivity analysis, the risk factor associated with both CRS type 2 and 4 were kidney dysfunction, albuminuria, and mineral bone disorder (higher alkaline phosphatase and FGF23), inflammation (TNF-α), and fibrotic factor (GDF-15), while diabetes, CVD, systolic blood pressure, waist circumference, anemia, HbA1c, and volume overload were more strongly associated with CRS type 2 compared to CRS type 4. Conclusion This study indicates that education level, history of CVD, kidney dysfunction, albuminuria, mineral bone disorder, diabetes control, anemia, volume overload, inflammation, and fibrotic factors are associated with progressive CRS. Many of these risk factors are modifiable. Further studies are warranted to assess the benefits of specific interventions to improve CRS outcomes.