Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial.

BACKGROUND: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD. METHODS: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90. RESULTS: Of 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29-0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0-7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9-8.1). CONCLUSIONS: In patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy. TRIAL REGISTRATION: NCT03434028 (2018-02-09), BioLINCC 14149.

Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6.

Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive.

Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4.

Hypervolemia is associated with inflammation in hemodialysis (HD) patients. How hypervolemia triggers inflammation is not entirely known. We initiated a cross-sectional study enrolling 40 hemodialysis patients who were categorized into normovolemic (N; 23) and hypervolemic (H; 17) groups by bioimpedance measurement. A caspase activity assay in combination with a specific caspase-4 inhibitor was used to detect caspase-4 activity in isolated peripheral blood mononuclear cells (PBMCs). Transcription factors RelA (pS529) and RelB (pS552) were analyzed by phospho-flow cytometry. Serum endotoxins were detected by an amebocyte lysate-based assay, and IL-6 (interleukin-6) and TNF-α (Tumor necrosis factor-α) gene expression were detected using the ELISA technique. Hypervolemic patients were older, more frequently had diabetes and showed increased CRP and IL-6 levels. Caspase-4 activity, which is linked to intracellular endotoxin detection, was significantly elevated in H patients. While the frequency of RelA-expressing immune cells and the expression density in these cells did not differ, the monocytic frequency of cells positively stained for RelB (pS552) was significantly decreased in H patients. Increased caspase-4 activity in H patients may indicate a cause of inflammation in H patients. The post-translational modification of RelB (pS552) is linked to downregulation of NF-kB activity and may indicate the resolution of inflammation, which is more distinct in N patients compared to H patients. Therefore, both higher inflammatory loads and lower inflammatory resolution capacities are characteristics of H patients.

The Nephrology Nurse Practitioner's Diagnostic Guide to Hyponatremia.

Hyponatremia affects patients in various settings. Nurse practitioners often face challenges in the evaluation and treatment of hyponatremia, due to the existence in the literature of different clinical guidelines and various schematic models. This article describes a systematic approach to diagnosing hyponatremia.

Impact of Bioelectrical Impedance-Guided Fluid Management and Vitamin D Supplementation on Left Ventricular Mass in Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Hypervolemia and vitamin D deficiency occur frequently in patients receiving peritoneal dialysis and may contribute to left ventricular (LV) hypertrophy. The effect of bioelectrical impedance analysis (BIA)-guided volume management or vitamin D supplementation on LV mass among those receiving peritoneal dialysis is uncertain. STUDY DESIGN: Two-by-two factorial randomized controlled trial. SETTING & PARTICIPANTS: Sixty-five patients receiving maintenance peritoneal dialysis. INTERVENTION: BIA-guided volume management versus usual care and oral cholecalciferol 50,000 U weekly for 8 weeks followed by 10,000 U weekly for 44 weeks or matching placebo. OUTCOME: Change in LV mass at 1 year measured by cardiac magnetic resonance imaging. RESULTS: Total body water decreased by 0.9 + 2.4 (SD) L in the BIA group compared with a 1.5 ± 3.4 L increase in the usual care group (adjusted between-group difference: -2.4 [95% CI, -4.1 to -0.68] L, P = 0.01). LV mass increased by 1.3 ± 14.3 g in the BIA group and decreased by 2.4 ± 37.7 g in the usual care group (between-group difference: +2.2 [95% CI, -13.9 to 18.3] g, P = 0.8). Serum 25-hydroxyvitamin D concentration increased by a mean of 17.2 ± 30.8 nmol/L in the cholecalciferol group and declined by 8.2 ± 24.3 nmol/L in the placebo group (between-group difference: 28.3 [95% CI, 17.2-39.4] nmol/L, P < 0.001). LV mass decreased by 3.0 ± 28.1 g in the cholecalciferol group and increased by 2.0 ± 31.2 g in the placebo group (between-group difference: -4.5 [95% CI, -20.4 to 11.5] g, P = 0.6). LIMITATIONS: Relatively small sample size with larger than expected variation in change in LV mass. CONCLUSIONS: BIA-guided volume management had a modest impact on volume status with no effect on the change in LV mass. Vitamin D supplementation increased serum vitamin D concentration but had no effect on LV mass. FUNDING: Unrestricted Baxter International extramural grant and the Kidney Foundation of Canada. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01045980.

Assessment of Fluid Status by Bioimpedance Analysis and Central Venous Pressure Measurement and Their Association with the Outcomes of Severe Acute Kidney Injury.

Background and Objectives: Fluid disbalance is associated with adverse outcomes in critically ill patients with acute kidney injury (AKI). In this study, we intended to assess fluid status using bioimpedance analysis (BIA) and central venous pressure (CVP) measurement and to evaluate the association between hyperhydration and hypervolemia with the outcomes of severe AKI. Materials and Methods: A prospective study was conducted in the Hospital of the Lithuanian University of Health Sciences Kauno Klinikos. Forty-seven patients treated at the Intensive Care Unit (ICU) with severe AKI and a need for renal replacement therapy (RRT) were examined. The hydration level was evaluated according to the ratio of extracellular water to total body water (ECW/TBW) of bioimpedance analysis and volemia was measured according to CVP. All of the patients were tested before the first hemodialysis (HD) procedure. Hyperhydration was defined as ECW/TBW > 0.39 and hypervolemia as CVP > 12 cm H2O. Results: According to bioimpedance analysis, 72.3% (n = 34) of patients were hyperhydrated. According to CVP, only 51.1% (n = 24) of the patients were hypervolemic. Interestingly, 69.6% of hypovolemic/normovolemic patients were also hyperhydrated. Of all study patients, 57.4% (n = 27) died, in 29.8% (n = 14) the kidney function improved, and in 12.8% (n = 6) the demand for RRT remained after in-patient treatment. A tendency of higher mortality in hyperhydrated patients was observed, but no association between hypervolemia and outcomes of severe AKI was established. Conclusions: Three-fourths of the patients with severe AKI were hyperhydrated based on bioimpedance analysis. However, according to CVP, only half of these patients were hypervolemic. A tendency of higher mortality in hyperhydrated patients was observed.

NSAIDs in CKD: Are They Safe?

The management of pain in patients with chronic kidney disease (CKD) is challenging for many reasons. These patients have increased susceptibility to adverse drug effects due to altered drug metabolism and excretion, and there are limited safety data for use in this population despite a high pain burden. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been regarded as dangerous for use in patients with CKD because of their risk for nephrotoxicity and thus alternative classes of analgesics, including opioids, have become more commonly used for pain control in this population. Given the well-established risks that opioids and other analgesics pose, further characterization of the risk posed by NSAIDs in patients with CKD is warranted. NSAID use has been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension. The risk for these nephrotoxicity syndromes is modified by many comorbid conditions, risk factors, and characteristics of use, and in patients with CKD, the risk differs between levels of glomerular filtration rate. In this review, we offer recommendations for the cautious use of NSAIDs in the CKD population after careful consideration of these risk factors on an individualized basis.

Diagnosis and Management of Disorders of Body Tonicity-Hyponatremia and Hypernatremia: Core Curriculum 2020.

Overall body fluid concentration is regulated within a narrow range by the concerted action of the hypothalamic-pituitary axis to influence water intake through thirst and water excretion via the effect of vasopressin, or antidiuretic hormone, on renal collecting duct water permeability. Sodium is the principal extracellular cation; abnormalities in overall effective body fluid concentration, or tonicity, manifest as disturbances in serum sodium concentration. Depending on its severity and chronicity, hyponatremia can lead to significant symptoms, primarily related to central nervous system function. Failure to correct hyponatremia can lead to permanent neurologic damage, as can over rapid correction. It is thus essential to stay within specific limits for correction, particularly for chronic hyponatremia. Hypernatremia also leads to central nervous system dysfunction, although goals for its correction rate are less well established. This Core Curriculum article discusses the normal regulation of tonicity and serum sodium concentration and the diagnosis and management of hypo- and hypernatremia.

High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output-Guided Fluid Restriction.

BACKGROUND: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). METHODS: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). RESULTS: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P = .012), while preload parameters and consciousness remained stable. CONCLUSION: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT.

The improvement of QRS-T angle as a manifestation of reverse electrical remodeling following renal transplantation in end-stage kidney disease patients on haemodialysis.

BACKGROUND: Successful renal transplantation (RT) reverses some of the cardiac changes and reduces cardiac mortality in hemodialysis (HD) patients. Widened QRS-T angle reflects both ventricular repolarization and depolarization. It is considered a sensitive and strong predictor of heart ventricular remodeling as well as a powerful and independent risk stratifier suitable in predicting cardiac events in various clinical settings. The study aimed to assess the influence of the RT on QRS-T angle and to evaluate factors influencing QRS-T changes in renal transplanted recipients (RTRs). METHODS: Fifty-four selected HD patients who have undergone RT were included. Blood chemistry, echocardiography, and QRS-T angle were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT. RESULTS: An improvement of echocardiographic parameters was observed. The dynamics of changes in individual parameters were, however, variable. QRS-T angle correlated with echocardiographic parameters. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the third month of follow-up. The second decrease of QRS-T angle was observed after 1 year of follow-up. The QRS-T angle was higher in RTRs compared with controls during each evaluation. Multivariable analysis demonstrated that the decrease of left ventricle enddiastolic volume was an independent predictor of early QRS-T angle improvement. The increase of left ventricle ejection fraction was found to be the independent predictor of the late QRS-T angle improvement. CONCLUSIONS: RT induces biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.

Effect of ingesting carbohydrate only or carbohydrate plus casein protein hydrolysate during a multiday cycling race on left ventricular function, plasma volume expansion and cardiac biomarkers.

PURPOSE: Multiday racing causes mild left ventricular (LV) dysfunction from day 1 that persists on successive days. We evaluated ingesting casein protein hydrolysate-carbohydrate (PRO) compared with carbohydrate-only (CHO) during a 3-day mountain bike race. METHODS: Eighteen male cyclists were randomly assigned to ingest 6.7% carbohydrate without (CHO) or with 1.3% casein hydrolysate (PRO) during racing (~ 4-5 h/day; 68/71/71 km). Conventional LV echocardiography, plasma albumin content, plasma volume (PV) and blood biomarkers were measured before day 1 and post race on day 3. RESULTS: Fourteen cyclists (n = 7 per group) completed the race. PV increased in CHO (mean increase (95% CI), 10.2% (0.1 to 20.2)%, p = 0.045) but not in PRO (0.4% (- 6.1 to 6.9)%). Early diastolic transmitral blood flow (E) was unchanged but deceleration time from peak E increased post race (CHO: 46.7 (11.8 to 81.6) ms, p = 0.019; PRO: 24.2 (- 0.5 to 48.9) ms, p = 0.054), suggesting impaired LV relaxation. Tissue Doppler mitral annular velocity was unchanged in CHO, but in PRO septal early-to-late diastolic ratio decreased (p = 0.016) and was compensated by increased lateral early (p = 0.034) and late (p = 0.012) velocities. Systolic function was preserved in both groups; with increased systolic lateral wall velocity in PRO (p = 0.002). Effect size increase in serum creatine kinase (CK) activity, CK-MB and C-reactive protein concentrations was less in PRO than CHO (Cohen's d mean ± SD, PRO: 2.91 ± 2.07; CHO: 7.56 ± 4.81, p = 0.046). CONCLUSION: Ingesting casein hydrolysate with carbohydrate during a 3-day race prevented secondary hypervolemia and failed to curb impaired LV relaxation despite reducing tissue damage and inflammatory biomarkers. Without PV expansion, systolic function was preserved by lateral wall compensating for septal wall dysfunction.

Chronic venous insufficiency: a new concept to understand pathophysiology at the microvascular level - a pilot study.

OBJECTIVES: The real mechanism for the development of the later stages of chronic venous insufficiency still remains unclear. Venous hypervolemia and microvascular ischemia have been reported to be the consequences of venous insufficiency. The aim of this study was to investigate the effects of induced venous hypovolemia by dorsiflexion exercise in patients with venous leg ulcers. METHODS: Thirty-six participants, all of whom had an ankle brachial pressure index between 0.8 and 1.2 mmHg, were chosen for this study. The participants were divided into two groups: Group A, a non-exercise group and Group B which performed regular exercise in the form of dorsiflexion. The basic assessment, including the history and examination, ankle-brachial pressure index (ABPI), Duplex scan and tcPO2 measurements, was performed on two occasions at the beginning of the trial and after three months. RESULTS: The tcPO2 level was low in the beginning in all the subjects, but the picture was different at the end of the trial. There was a significant increase in the tcPO2 level (p<0.001) in the patients who performed exercise while there was no difference in the measurements (p>0.05) in the non-exercise group. CONCLUSIONS: Induced venous hypovolemia through regular evacuation of the peripheral venous system improved tissue oxygenation at skin level. Venous hypervolemia may be the main contributing factor for the development of venous hypoxia and microvascular ischemia.

Serum ADMA, endothelial dysfunction, and atherosclerosis in hypervolemic hemodialysis patients

Background/aim: Asymmetric dimethyl arginine (ADMA) is a strong predictor of cardiovascular disease and mortality in patients under hemodialysis treatment. We aimed to investigate the relationship among volume status, endothelial dysfunction, and ADMA in hemodialysis patients. Materials and methods: A total of 120 patients with a history of hemodialysis treatment were included. ADMA and CRP were measured. Echocardiographic evaluation and carotid artery intima-media thickness (CIMT) measurements were performed. Patients were divided into two groups according to clinical evaluation, ultrafiltration rate, vena cava inferior diameter (VCI), and cardiothoracic index (CTI); the two groups were hypervolemic and normovolemic. Results: The hypervolemic group included 61 patients while the normovolemic group included 59 patients. CIMT was higher in the hypervolemic group, but this result was not statistically significant (0.95 mm versus 0.85 mm, P = 0.232). There was a statistically significant difference between the hypervolemic and normovolemic groups in terms of ADMA (P < 0.001) (0.69 ± 0.57 µmol/L and 0.41 ± 0.04 µmol/L, respectively). Positive correlations were observed between serum ADMA, VCI, CTI, CRP, CIMT, and cardiac mass (P < 0.001, P = 0.016, P < 0.001, P = 0.006, P = 0.022, respectively), and negative correlations were observed between ADMA and ejection fraction and albumin (P = 0.024, P = 0.024, respectively). In multiple linear regression analysis, ADMA was independently associated with age, systolic blood pressure, CTI, and volume status. Conclusion: ADMA may be a potential determinant of hypervolemia as well as atherosclerosis in patients under hemodialysis treatment.

Fluid management of the neurological patient: a concise review.

Maintenance fluids in critically ill brain-injured patients are part of routine critical care. Both the amounts of fluid volumes infused and the type and tonicity of maintenance fluids are relevant in understanding the impact of fluids on the pathophysiology of secondary brain injuries in these patients. In this narrative review, current evidence on routine fluid management of critically ill brain-injured patients and use of haemodynamic monitoring is summarized. Pertinent guidelines and consensus statements on fluid management for brain-injured patients are highlighted. In general, existing guidelines indicate that fluid management in these neurocritical care patients should be targeted at euvolemia using isotonic fluids. A critical appraisal is made of the available literature regarding the appropriate amount of fluids, haemodynamic monitoring and which types of fluids should be administered or avoided and a practical approach to fluid management is elaborated. Although hypovolemia is bound to contribute to secondary brain injury, some more recent data have emerged indicating the potential risks of fluid overload. However, it is acknowledged that many factors govern the relationship between fluid management and cerebral blood flow and oxygenation and more research seems warranted to optimise fluid management and improve outcomes.

CT perfusion cerebral blood volume does not always predict infarct core in acute ischemic stroke.

We investigated the practical clinical utility of the CT perfusion (CTP) cerebral blood volume (CBV) parameter for differentiating salvageable from non-salvageable tissue in acute ischemic stroke (AIS). Fifty-five patients with AIS were imaged within 6 h from onset using CTP. Admission CBV defect (CBVD) volume was outlined using previously established gray and white matter CBV thresholds for infarct core. Admission cerebral blood flow (CBF) hypoperfusion and CBF/CBV mismatch were visually evaluated. Truncation of the ischemic time-density curve (ITDC) and hypervolemia status at admission, recanalization at 24-h CT angiography, hemorrhagic transformation (HT) at 24 h and/or 7-day non-contrast CT (NCCT), final infarct volume as indicated by 3-month NCCT defect (NCCTD) and 3-month modified Rankin Score were determined. Patients with recanalization and no truncation had the highest correlation (R = 0.81) and regression slope (0.80) between CBVD and NCCTD. Regression slopes were close to zero for patients with admission hypervolemia with/without recanalization. Hypervolemia underestimated (p = 0.02), while recanalization and ITDC truncation overestimated (p = 0.03) the NCCTD. Among patients with confirmed recanalization at 24 h, 38 % patients had an admission CBF/CBV mismatch within normal appearing areas on respective NCCT. 83 % of these patients developed infarction in admission hypervolemic CBF/CBV mismatch tissue. A reduction in CBV is a valuable predictor of infarct core when the acquisition of ITDC data is complete and hypervolemia is absent within the tissue destined to infarct. Raised or normal CBV is not always indicative of salvageable tissue, contrary to the current definition of penumbra.

Bioimpedance spectroscopy for the differential diagnosis of hyponatremia.

BACKGROUND: Hyponatremia is classified according to volume status with the help of physical examination, biochemical measures, urine and serum osmolalities, and echocardiography. Bioimpedance spectroscopy (BIS) has been getting popularity for revealing tissue compositions of various patient groups. The aim of this observational study was to investigate the role of BIS for the differential diagnosis of hyponatremia (ClinicalTrials.gov Identifier: NCT01838759). PATIENTS AND METHODS: Personal characteristics of age, sex, weight, height, and blood pressure were recorded. Body composition monitor (BCM) was used for hydration status for each individual. Primary outcome was investigated by the accuracy of volume status measured by BIS. STATISTICS: Kappa statistic (K) is a measure of agreement between two sources, which is measured on a binary scale (i.e., condition present/absent). K statistic can take values between 0 and 1: poor agreement: K < 0.20, fair agreement: 0.2.0-0.3.9, moderate agreement: 0.40-0.59, substantial: 0.60-0.79, very good agreement: 0.80-1.00. RESULTS: Fifty-eight hyponatremia-diagnosed patients, 32 (55.2%) of male with the mean age of 65.2 ± 11 (40-89) years were included. Kappa statistic (K) were very good (K = 0.925) for male (p < 0.00), substantial agreement (K = 0.601) for female (p < 0.002) with the use of BIS for the differential diagnosis of either hypo or hypervolemia in hyponatremic patients compared with gold standard tests which were the combination of echocardiography, serum, and urine osmolality biochemical tests, and physical examination. CONCLUSION: Bioimpedance spectroscopy is a practical and an inexpensive method. This is the first study in the literature showing the role of BIS for the determination of the volume status and differential diagnosis of hyponatremia when compared with echocardiography.

Inflammation is associated to volume status in peritoneal dialysis patients.

AIM: The aim of this study is to investigate whether there is a relationship between inflammation and volume status in patients underwent peritoneal dialysis (PD). PATIENTS AND METHOD: This cross-sectional study included 159 PD patients. The median duration of PD was 17 (range, 1-151) months. All patients were examined using bioelectrical impedance analysis to estimate the ratio of extracellular water to total body water (ECW/TBW), which was used to assess their volume status. The patients were categorized as having one of the following three volume statuses: hypervolemic (above +2 SD from the mean, which was obtained from healthy controls), normovolemic (between +2 SD and -2 SD), or hypovolemic (below -2 SD from the mean). Five patients with hypovolemia were excluded from the study. Fifty-six patients were hypervolemic whereas 98 patients were euvolemic. High-sensitive C-reactive protein (hs-CRP) levels were measured to evaluate inflammation in all patients. RESULTS: hs-CRP value levels were significantly higher in hypervolemic patients compared with euvolemic patients [7.1 (3.1-44.0) mg/L vs. 4.3 (3.1-39.6), p: 0.015, respectively]. Left ventricular hypertrophy was more frequent in hypervolemic patients compared with euvolemic patients (53.6% vs. 30.6%, p: 0.004, respectively). ECW/TBW ratio positively correlated with hs-CRP (r: 0.166, p: 0.039). Gender, hs-CRP, and residual Kt/V urea were found to be independent risk factors for hypervolemia in multivariate analysis. CONCLUSION: Inflammation is associated with hypervolemia in PD patients. Residual renal functions play an important role to maintain euvolemia in PD patients.

Higher NT-proBNP levels and the risk of intradialytic hypotension at hemodialysis initiation.

INTRODUCTION: Elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) is a potent predictor of adverse outcomes in hemodialysis initiation. These patients often experience intradialytic hypotension, which may partially reflect cardiac dysfunction, but the association of NT-proBNP with intradialytic hypotension is not clear. METHODS: We performed a post hoc analysis of a randomized trial that tested mannitol versus placebo in 52 patients initiating hemodialysis (NCT01520207). NT-proBNP was measured prior to the first and third sessions (n = 87). Mixed-effects models (adjusting for randomized treatment, sex, race, age, diabetes, heart failure, catheter use, pre-dialysis systolic blood pressure, pre-dialysis weight, ultrafiltration volume, serum sodium, bicarbonate, urea nitrogen, phosphate, albumin, hemoglobin, and session length) were fit to examine the association of NT-proBNP with systolic blood pressure decline (pre-dialysis minus nadir systolic blood pressure). Additionally, mixed-effects Poisson models were fit to examine the association with intradialytic hypotension (≥20 mmHg decline in systolic blood pressure). FINDINGS: Mean age was 55 ± 16 years; 33% had baseline heart failure. The median NT-proBNP was 5498 [25th-75th percentile 2011, 14,790] pg/mL; 26 sessions (30%) were complicated by intradialytic hypotension. In adjusted models, each unit higher log-NT-proBNP was associated with 6.0 mmHg less decline in systolic blood pressure (95%CI -9.2 to -2.8). Higher pre-dialysis NT-proBNP, per log-unit, was associated with a 52% lower risk of intradialytic hypotension (IRR 0.48, 95%CI 0.23-0.97), without evidence for effect modification by randomized treatment (P-interaction = 0.17). DISCUSSION: In patients initiating hemodialysis, higher NT-proBNP is associated with less decline in intradialytic systolic blood pressure and lower risk of intradialytic hypotension. Future studies should investigate if higher pre-dialysis NT-proBNP levels may identify patients who might tolerate more aggressive ultrafiltration.

[Effectiveness of urea administration for the treatment of hyponatremia in heart failure]. / Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca.

OBJECTIVES: To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). METHODS AND RESULTS: This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. CONCLUSIONS: Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia.

An Association Between Prophylactic Hypervolemia-Augmented Blood Pressure and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage Who Underwent Delayed Clipping.

BACKGROUND: The prior trials investigating triple-H therapy for preventing delayed cerebral ischemia (DCI) enrolled patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent early aneurysm therapy within 3 days. However, surgical clipping might be performed during 4-7 days that high incidence cerebral vasospasm is likely. We examined effects of hypervolemia-augmented blood pressure (HV-ABP) protocol on DCI prevention when clipping was delayed. METHODS: The study enrolled aSAH patients hospitalized during 2013-2019 who underwent clipping 4-7 days after rupture in a university hospital in Thailand. DCI and secondary outcomes were compared among patients who achieved the HV-ABP protocol (3-5 L/day fluid intake and 140-180 mmHg systolic blood pressure maintained for 72 hours postoperatively) and those who did not. The intervention-outcome associations were estimated using logistic regression for the whole group and a patient subgroup with similar propensity scores (PS) for protocol achievement. RESULTS: One hundred seventy-seven aSAH patients were clipped 4-7 days after rupture; 97 patients (54.8%) achieved the HV-ABP protocol, while 80 patients (45.2%) did not. One hundred twenty-two patients with one-to-one PS matching reduced the originally unequal patient characteristics. The observed DCI was lower in patients with protocol-achieved (8.3%) than in their nonachieved counterparts (22.5%). This resulted in an association with the HV-ABP intervention with adjusted odds ratios of 0.201 (95% confidence interval, 0.066-0.613) in the whole sample and 0.228 (0.065-0.794) in the PS-matched subsample. No statistically significant differences in the secondary outcomes were found. CONCLUSIONS: Achieving the targets recommended in the HV-ABP protocol was associated with reducing the DCI incidence in patients with aSAH who underwent delayed clipping.