Body Fluid Status Research Articles

The Relationship between Body Compositions and Serum Vitamin D Levels in Obese Adolescents

Purpose: Obesity and vitamin D deficiency is a significant public health problem with increasing frequency in childhood. Although numerous studies explored the correlation between obesity and vitamin D, the study is aimed to investigate such relationship in consideration of few/no studies on vitamin D and body compositions in obese people. Methods: A total of 62 adolescents aged 12 to 18 were included in the study, comprising 33 obese adolescents and 29 with normal weight. Blood samples were analyzed for 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (ALP), parathyroid hormone (PTH), insulin, C-reactive protein (CRP), total cholesterol, LDL cholesterol (LDL), triglycerides (TG), and HDL cholesterol (HDL). Body fluid status and composition were assessed using bioimpedance spectroscopy (BIS) for both the obese and control groups. Results: Total body water (TBW), extracellular water (ECW), intracellular water (ICW), ECW/ICW (E/I) ratio, lean tissue index (LTI), adipose tissue index (FTI), lean tissue mass (LTM), adipose tissue mass (ATM), body cell mass (BCM) values were significantly higher in the obese group in comparison with the control group (p ˂ 0.05). There was no significant difference in 25(OH)D levels in the obese and control groups (p ˃ 0.05). The distribution of 25(OH)D values below and above 20 did not differ significantly in the obese and control groups (p ˃ 0.05). Cholesterol, insulin and HOMA-IR values were detected significantly higher in the obese group than in the control group (p ˂ 0.05). HDL and Ca values were significantly lower in the obese group than in the control group (p ˂ 0.05). A significant positive correlation was discovered between BMI value and TBW, ECW, ICW, E/I, LTI, FTI, LTM, ATM, BCM values (p ˂ 0.05). A significant positive correlation was discovered between HOMA IR value and TBW, ECW, ICW, E/I, FTI, FAT, ATM values (p< 0.05). No significant correlation was encountered between ....

Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.

We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.

#1157 Body mass and fluid balance in dialysis: global profiles in Apollo Dial DB

Abstract Background and Aims Fluid management is a fundamental component of dialysis care. Achieving euvolemia and avoiding fluid overload can be challenging in dialysis. Apollo Dial DB, an anonymised dialysis database from a global kidney care network, was used to gain deeper insights in patterns of patient body mass and fluid balance during dialysis treatments worldwide. Method Apollo Dial DB, a global anonymised dialysis database, contains real-world data from patients in 40 countries beginning January 2018 throughout March 2021. Parameters include demographics, diagnoses, laboratories, medications, treatments, quality of life, and outcomes. This analysis assessed body mass and fluid status parameters on patients in Asia-Pacific (AP), Europe, Middle East, and Africa (EMEA), Latin America (LA), Northern America (NA). In addition, bioimpedance for body compositions of patients was assessed as it was available in AP, EMEA, and LA. Results The first version of the Apollo Dial DB includes data on 543, 169 patients, with 4.6% from AP, 13.9% from EMEA, 7.0% from LA, and 74.5% from NA countries. EMEA and NA have a higher proportion of patients in the bigger height categories versus the AP and LA regions (Table 1). There is a difference in mean body weight post dialysis of more than 10 kg between regions; the highest weights were observed in EMEA and NA in contrast to the AP and LA regions. Average albumin levels were consistent in all global regions. Intradialytic weight gain is lowest in EMEA at 1.8 kg and highest in NA at 2.2 kg between treatments. While ultrafiltration volume ranged from 2.0 L to 2.4 L, being the highest in AP and NA. Bioimpedance measures defining body compositions were available for the majority of patients in AP (59.3%), EMEA (86.9%), and LA (90.7%). Patient averages in EMEA are slightly higher for ATM, FTM, LTM, TBW than for LA and AP; this is somewhat explained by the differences in body weight between the cohorts (Fig. 1). Conclusion A descriptive analysis of the body mass and fluid status across minor and major regions bring to light key profiles and differences in the characteristics of dialysis patients across the world and fluid management practices in dialysis care. Differences in intradialytic weight gain may deserve further analysis considering the impact of dialysis modality on fluid balance, such as potential influences of convective therapies. These findings act as benchmarks for the nephrology community. Apollo Dial DB offers opportunities for investigators to conduct global analytics and advance kidney disease research.

Use of Bioelectrical Impedance Analysis to Explore the Effectiveness of Stellate Ganglion Block in Patients with Post-Stroke Complex Regional Pain Syndrome: A Retrospective Pilot Study.

Post-stroke complex regional pain syndrome (CRPS) poses challenges in pain assessment for survivors. Stellate ganglion block (SGB) is a treatment, but evaluating its effectiveness is difficult for patients with communication limitations. Edema, a prominent symptom, can serve as an evaluation marker. Bioelectrical impedance analysis (BIA), assessing body composition and fluid status, is used independently of patient cooperation. This retrospective, observational pilot study aims to explore BIA's utility as an assessment tool post-SGB, revealing the effects and time courses of a single SGB on the bodily composition of post-stroke CRPS patients. Seven patients received ultrasound-guided SGB with a 5 mL solution containing 4 mL of 0.25% bupivacaine hydrochloride and 40 mg of triamcinolone into the prevertebral muscle space. BIA compared measures between affected and unaffected arms. The affected arm had higher segmental body water (SBW) and extracellular water ratios before SGB (p = 0.028 and p = 0.018, respectively). The SBW of the affected side, the SBW ratio, and the 1 and 5 kHz SFBIA ratios improved over time (p = 0.025, 0.008, 0.001, and 0.005, respectively). Rapid improvement occurred around 3 days post-injection, with maximum effects within approximately 1 week, persisting up to 3 weeks. SGB successfully reduced edema in post-stroke CRPS patients, with BIA serving as a useful tool for follow-up, facilitating the development of efficient treatment plans.

SGLT2 Inhibitors Decrease Overhydration and Proteasuria in Patients with Chronic Kidney Disease: A Longitudinal Observational Study

Introduction: SGLT2 inhibitors are used to reduce the risk of progression of chronic kidney disease (CKD). In patients with type 2 diabetes, they have been found to reduce extracellular volume. Given the high prevalence of extracellular volume expansion and overhydration (OH) in CKD, we investigated whether SGLT2 inhibitors might correct these disturbances in CKD patients. Methods: CKD patients who started treatment with an SGLT2 inhibitor were investigated in this prospective observational study for 6 months. Body composition and fluid status were measured by bioimpedance spectroscopy. In addition, spot urine samples were analyzed for albuminuria, glucosuria, and urinary aprotinin-sensitive serine protease activity. Results: Forty-two patients (29% with diabetic/hypertensive CKD, 31% with IgA nephropathy; 88% dapagliflozin 10 mg, 10% dapagliflozin 5 mg, 2% empagliflozin 20 mg; median eGFR 46 mL/min/1.73 m2 and albuminuria 1,911 mg/g creatinine) participated in the study. Median glucosuria increased to 14 (10–19) g/g creatinine. At baseline, patients displayed OH with +0.4 (−0.2 to 2.2) L/1.73 m2, which decreased by 0.5 (0.1–1.2) L/1.73 m2 after 6 months. Decrease of OH correlated with higher OH at BL, decrease of albuminuria, glucosuria, and urinary aprotinin-sensitive protease activity. Adipose tissue mass was not significantly reduced after 6 months. Conclusion: SGLT2 inhibitors reduce OH in patients with CKD, which is pronounced in the presence of high albuminuria, glucosuria, and urinary aprotinin-sensitive protease activity.

An observational study on salivary conductivity for fluid status assessment and clinical relevance in acute ischemic stroke during intravenous fluid hydration

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31–22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke.

Fluid homeostatic action of dapagliflozin in patients with chronic kidney disease: the DAPA-BODY Trial.

Sodium glucose cotransporter 2 (SGLT2) inhibitors have both glucose-lowering and diuretic effects. We recently reported that the SGLT2 inhibitor dapagliflozin exerts short-term fluid homeostatic action in patients with chronic kidney disease (CKD). However, the long-term effects of SGLT2 inhibitors on body fluid status in patients with CKD remain unclear. This was a prospective, non-randomized, open-label study that included a dapagliflozin treatment group (n = 73) and a control group (n = 24) who were followed for 6 months. Body fluid volume was measured using a bioimpedance analysis device. The extracellular water-to-total body water ratio (ECW/TBW), a predictor of renal outcomes, was used as a parameter for body fluid status (fluid retention, 0.400 ≤ ECW/TBW). Six-month treatment with dapagliflozin significantly decreased ECW/TBW compared with the control group (-0.65% ± 2.03% vs. 0.97% ± 2.49%, p = 0.0018). Furthermore, dapagliflozin decreased the ECW/TBW in patients with baseline fluid retention, but not in patients without baseline fluid retention (-1.47% ± 1.93% vs. -0.01% ± 1.88%, p = 0.0017). Vasopressin surrogate marker copeptin levels were similar between the control and dapagliflozin groups at 6 months (32.3 ± 33.4 vs. 30.6 ± 30.1 pmol/L, p = 0.8227). However, dapagliflozin significantly increased the change in copeptin levels at 1 week (39.0% ± 41.6%, p = 0.0010), suggesting a compensatory increase in vasopressin secretion to prevent hypovolemia. Renin and aldosterone levels were similar between the control and dapagliflozin groups at 6 months, while epinephrine and norepinephrine (markers of sympathetic nervous system activity) were significantly lower in the dapagliflozin group than in the control group. In conclusion, the SGLT2 inhibitor dapagliflozin ameliorated fluid retention and maintained euvolemic fluid status in patients with CKD, suggesting that SGLT2 inhibitors exert sustained fluid homeostatic actions in patients with various fluid backgrounds. Clinical trial registration: https://www.umin.ac.jp/ctr/, identifier [UMIN000048568].

Role of Vena Cava Inferior Ultrasound in Volume Assesment

Regulation of body fluid volume is a key concern for physicians in intensive care units. In intensive care, it is most important to determine the intracellular fluid status because it directly affects the volume status of the patient. Ultrasonography appears to be a useful tool for the assessment of body fluid status. The gold standard for measuring central venous pressure (CVP) is a central venous catheter. Vena cava inferior ultrasound (US-VCI) has been proposed as the non-invasive technique of choice for CVP assessment due to its wide availability, low costs, and ease of use. While a depleted IVC is often observed in hypovolemic patients, typically the IVC is dilated in a hypervolemic condition with a less pronounced or null respiratory collapse in the appropriate clinical context. respiratory variability in VCI diameteris known as the caval index (collapsibility index=VCImaxVCImin /VCImax) and is considered to reflect the intravascular volume state. According to the current updated American and European guidelines, an IVC diameter ≤2.1 cm and collapsibility >50% during inspiration suggest a RAP between 0–5 mm Hg while a diameter >2.1 cm with <50% inspiratory collapse indicates a high RAP of 10–20 mmHg. Primarily because of complicated pathophysiological mechanisms, ultrasound measurement of VCI should not be used as the only parameter in the assessment of volemic status.

RENAL10: Urinary Vitamin D Binding Protein and Kidney Injury Molecule-1 May Predict the Risk of Acute Kidney Injury in Heart Failure Patients Undergoing CF-LVAD Implantation

Background: Renal dysfunction in advanced heart failure (HF) and durable mechanical circulatory support (MCS) is common and harmful, yet current tests are inaccurate and confounded by body composition, fluid status, and other factors. Newer biomarkers more directly reflecting specific aspects of renal health/function have been tested in other fields but have yet to be tested in this complex setting. Urine vitamin-D-binding protein (uVDBP) and urine kidney injury molecule-1 (uKIM-1) have been shown to identify and stage severity of parenchymal kidney injury in several settings. The purpose of our study is to explore the potential role of uVDBP and uKIM-1 as biomarkers of acute renal damage among HF patients receiving CF-LVAD support. Methods: Our cohort included 29 HF patients undergoing CF-LVAD implantation. Early morning voided urine was collected immediately pre-implantation. Measurements of uVDBP and uKIM-1 were performed with ELISA kits and data were normalized to urine creatinine (ng/mg Cr.). Relationships of uVDBP and uKIM-1 and important baseline clinical characteristics (presence of kidney dysfunction, defined as eGFR<60 ml/min/1.73m2, and hemodynamic instability, defined as INTERMACS 1/2) were assessed using the Wilcoxon test. Relationships of baseline uVDBP and uKIM-1 (log2 transformed) with risk of acute kidney Injury (AKI) developing within 90 days after CF-LVAD implant were assessed, using logistic regression with adjustment for baseline kidney function and for baseline hemodynamic stability. AKI was assessed using RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Results: The cohort (n=29), had mean (SD) age 58 (14) years, 17.2% were female, and destination therapy goal for 96.6%. Baseline kidney dysfunction and hemodynamic instability were present in 37.9% and 44.8% of patients respectively, and 44.8% had AKI within 90 days. Baseline uVDBP [median (IQR)] was 0.88 (0.20-2.3) ng/mg Cr., and baseline uKIM-1 [median (IQR)] was 0.013 (0.0032-0.042) ng/mg Cr. Baseline uVDBP was found to be significantly associated with baseline kidney risk category (p <0.001), with higher uVDBP associated with worse baseline kidney health/function risk (assessed by combination of baseline low kidney function and hemodynamic instability, Fig.1A). Baseline uKIM-1 was significantly associated with baseline kidney function but not with baseline kidney risk category (Fig.1B). Two-fold higher baseline uKIM-1 was associated with nearly two-fold increased odds of 90-day AKI (Table.1). Similar results were obtained for baseline uVDBP. Conclusions: We have demonstrated that both uVDBP and uKIM-1 may provide additional information about baseline kidney health beyond that provided by serum creatinine-based and hemodynamic instability-based measures, assessed by risk for adverse 90-day kidney outcomes. Further study in larger cohorts is needed. Table 1. - Association of baseline urine markers with post-implant AKI Odds ratios (95% confidence intervals) Unadjusted Model 1 Model 2 uKIM-1 Per two-fold greater uKIM-1 1.98 (1.28-3.71) 4.39 (1.79-22.2) 8.76 (2.03-311) uVDBP Per two-fold greater uVDBP 1.99 (1.27-3.68) 2.25 (1.23-4.90) 7.74 (2.07-296) Model 1 was adjusted for baseline kidney dysfunction;Model 2 was adjusted for baseline kidney dysfunction and baseline hemodynamic instability

The Role of Nitric Oxide in the Micro- and Macrovascular Response to a 7-Day High-Salt Diet in Healthy Individuals.

This study aimed to investigate the specific role of nitric oxide (NO) in micro- and macrovascular response to a 7-day high-salt (HS) diet, specifically by measuring skin microvascular local thermal hyperemia and the flow-mediated dilation of the brachial artery, as well as serum NO and three NO synthase enzyme (NOS) isoform concentrations in healthy individuals. It also aimed to examine the concept of non-osmotic sodium storage in the skin following the HS diet by measuring body fluid status and systemic hemodynamic responses, as well as serum vascular endothelial growth factor C (VEGF-C) concentration. Forty-six young, healthy individuals completed a 7-day low-salt diet, followed by a 7-day HS diet protocol. The 7-day HS diet resulted in impaired NO-mediated endothelial vasodilation in peripheral microcirculation and conduit arteries, in increased eNOS, decreased nNOS, and unchanged iNOS concentration and NO serum level. The HS diet did not change the volume of interstitial fluid, the systemic vascular resistance or the VEGF-C serum level. These results indicate that the 7-day HS-diet induces systemic impairment of NO-mediated endothelial vasodilation, while dissociation in the eNOS and nNOS response indicates complex adaptation of main NO-generating enzyme isoforms to HS intake in healthy individuals. Our results failed to support the concept of non-osmotic sodium storage.

Posterior reversible encephalopathy syndrome: A conundrum of nephrotic syndrome complication

Nephrotic syndrome is a kidney disease with proteinuria, hypoalbuminemia, and edema. One rare, potentially life-threatening complication of nephrotic syndrome is posterior reversible encephalopathy syndrome (PRES). Sudden episodes of neurological symptoms such as headache, confusion, seizures, or focal neurological deficits with radiological findings of white matter abnormalities in the parietal and occipital lobes characterize it. Multiple factors predispose an individual with nephrotic syndrome to PRES, such as uncontrolled hypertension, reduced serum albumin levels, administration of drugs (cyclosporine, tacrolimus), anasarca, disturbed body fluid status and renal insufficiency. Here, we report a case of PRES in a seven-year-old girl with nephrotic syndrome who presented with high blood pressure while admitted to the ward. Her neurological symptom rapidly recovered after the control of hypertension. Recurrence of acute severe hypertension, nephrotic state (edema/ hypoalbuminemia), and renal insufficiency may lead to recurrent PRES. Thus, early treatment of trigger factors, especially of hypertension, is vital to reduce the episodes of PRES.

Importance of Bio-electrical Impedance for Measurement of Body Fluid Status in Chronic Kidney Disease Patients on Maintenance Haemodialysis: A Narrative Review

Assessing the precise body water status in patients with renal disorders is crucial for their health. It has been reported that chronic fluid overload is present even in the early stages of renal insufficiency. If volume overload in a patient with chronic renal failure is not controlled, serious problems such as pulmonary oedema, cardiac remodelling, and diastolic heart failure can develop. Bioelectrical Impedance Analysis (BIA) has emerged as one of the most useful tools, although randomised clinical studies are lacking to support its universal use. Early management of hydration may improve clinical outcomes, as it allows for personalised dialysis prescriptions and nutritional support. BIA practice is utilised as non invasive health monitoring for Body Composition (BC). BIA is a practical and inexpensive method. Moreover, BIA parameters estimated for disease prognosis analysis have been found to be reasonably predictable for both patient status and healthcare. Additionally, BIA is a simple, accurate, portable, quick, easy, and low-cost method. In patients with End-stage Renal Disease (ESRD) undergoing maintenance Haemodialysis (HD) treatment, excessive fluid volume is considered a risk factor for death. Furthermore, fluid elimination to achieve Dry Weight (DW) is a crucial component of HD treatment for ESRD patients. DW is an important concept related to patients undergoing HD. Conventional methods seem to be time-consuming and operator-dependent. BIA is a new and simple method that has been reported to accurately estimate DW. Estimating the dry weight of HD patients is a challenging task. Many tools are available, but not every HD centre has access to them. Several strategies have been used to develop a more standardised method of assessing dry weight in HD patients. The Bio-impedance Spectroscopy (BIS) device has been validated against gold standard methods of volume assessment. Body composition monitoring appears to be a helpful diagnostic tool that reasonably complements existing clinical methods in assessing the DW of HD patients. BIS identifies Fluid Overload (FO) as a virtual "Over Hydration (OH)" compartment, which is calculated from the difference between the measured extracellular volume and the predicted values based on a fixed hydration of lean and adipose tissue mass.

Body fluid status in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Abstract Introduction Body fluid status can be determined by plasma volume status and extracellular water to total body water (ECW/TBW) ratio and is a well-known parameter associated with survival in patients with chronic heart failure (1–3). However, its prognostic impact in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Methods 409 patients with PAH and CTEPH who entered the Giessen PH registry were included in this study (4). Plasma volume status was estimated using Duarte formula (ePVS = (1 − hematocrit) / hemoglobin × 100). ECW was calculated via Peters formula ((−2.47 × 0.842 + 8.76 × body surface area) for men and (−1.96 × 0.572 + 8.05 × body surface area) for women) and TBW via Watson formula ((2.447 − [0.09516 × age] + [0.1073 × height] + [0.3362 × body weight]) for men and (−2.097 + [0.1069 × height] + [0.2466 × body weight]) for women). Statistical analyzes were performed with R (The R Foundation). Results Median age of the included patients was 65 [53, 74] years. Median ePVS and ECW/TBW ratio were 4.5 [3.9, 5.5] and 0.39 [0.37, 0.40]. Correlation analyses revealed that ePVS correlates with pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), cardiac index, and mixed venous oxygen saturation (SvO2), whereas ECW/TBW ratio did not correlate with pulmonary hemodynamics. Accordingly, univariate Cox regression revealed that ePVS but not ECW/TBW ratio was associated with mortality (HR: 1.18 [1.02, 1.37]). ePVS remained as an independent prognostic parameter in multivariate Cox regression analysis. Patients with high ePVS showed significantly decreased survival rates (log-rank p&amp;lt;0.001). Conclusion ePVS but not ECW/TBW ratio is associated with prognostic parameters such as PVR, cardiac index and SvO2. Thus, ePVS may be an independent prognostic parameter in patients with PAH and CTEPH. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

SGLT2 inhibitor and loop diuretic induce different vasopressin and fluid homeostatic responses in nondiabetic rats.

Loop diuretics are commonly used diuretics in the treatment of fluid retention but induce hypovolemia-related renal dysfunction. Na+-glucose cotransporter 2 (SGLT2) inhibitors induce osmotic diuresis, but body fluid volume is maintained by stimulating vasopressin-induced fluid intake and collecting duct water reabsorption as previously reported in diabetic rats. We aimed to test the hypothesis that unlike SGLT2 inhibitors, loop diuretics lack activation of similar fluid homeostatic mechanisms. Nondiabetic male Sprague-Dawley rats were treated daily by oral gavage with vehicle, the SGLT2 inhibitor ipragliflozin (5 mg/kg), or the loop diuretic furosemide (50 mg/kg) and monitored in metabolic cages for 2 or 7 days. Ipragliflozin and furosemide similarly increased urine volume on day 2. This was associated with increased serum Na+ concentration, urine vasopressin excretion, fluid intake, and solute-free water reabsorption in response to ipragliflozin but not to furosemide. Ipragliflozin maintained fluid balance (fluid intake - urine volume) on day 2 and total body water measured by bioimpedance spectroscopy and serum creatinine on day 7. In comparison, furosemide decreased fluid balance on day 2 and decreased total body water and increased serum creatinine on day 7. Furosemide, but not ipragliflozin, increased plasma renin activity, and systolic blood pressure was similar among the groups. In conclusion, the osmotic diuresis of the SGLT2 inhibitor increased serum Na+ concentration and the vasopressin-related stimulation of fluid intake and renal water retention maintained fluid balance, whereas the loop diuretic did not engage the compensatory vasopressin system. The data suggest differences in vasopressin and fluid homeostatic responses between SGLT2 inhibitors and loop diuretics.NEW & NOTEWORTHY In nondiabetic rats, the Na+-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin increased vasopressin-related stimulation of fluid intake and free water reabsorption and maintained fluid balance and serum creatinine, whereas the loop diuretic furosemide reduced vasopressin and induced a negative fluid balance followed by a subsequent increase in serum creatinine. This study suggests that differences in vasopressin secretion in response to a SGLT2 inhibitor or loop diuretic may contribute to differences in body fluid status and subsequent renal function.

Plasma and serum prorenin concentrations in diabetes, hypertension, and renal disease.

Although the renin-angiotensin-aldosterone system plays a crucial role in fluid homeostasis and cardiovascular disease pathophysiology, measurements of plasma prorenin levels are still unavailable in clinical practice. We previously found that prorenin molecules in human blood underwent significant posttranslational modifications and were undetectable using immunological assays that utilized antibodies specifically recognizing unmodified recombinant prorenin. Using a sandwich enzyme-linked immunosorbent assay that captures posttranslationally modified prorenins with their prosegment antibodies, we measured plasma and serum prorenin concentrations in 219 patients with diabetes mellitus, hypertension and/or renal disease and compared them with those of 40 healthy controls. The measured values were not significantly different from those of the healthy controls and were 1,000- to 100,000-fold higher than previously reported levels determined using conventional assay kits. Multiple regression analyses showed that body weight, serum albumin levels, and serum creatinine levels negatively correlated with plasma prorenin levels, while the use of loop diuretics was associated with elevated plasma prorenin levels. Blood pressure, HbA1c, and plasma renin activity were not independent variables affecting plasma prorenin levels. In contrast, serum prorenin levels were unaffected by any of the above clinical parameters. The association of the plasma prorenin concentration with indices reflecting body fluid status suggests the need to scrutinize its role as a biomarker, while serum prorenins are less likely to have immediate diagnostic value.

Urine Di-(2-ethylhexyl) Phthalate Metabolites Are Independently Related to Body Fluid Status in Adults: Results from a U.S. Nationally Representative Survey

Purpose: Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many daily products for decades. Previous studies have reported that DEHP exposure could induce renin–angiotensin–aldosterone system activation and increase epithelial sodium channel (ENaC) activity, which contributes to extracellular fluid (ECF) volume expansion. However, there is also no previous study to evaluate the association between DEHP exposure and body fluid status. Methods: We selected 1678 subjects (aged ≥18 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003–2004 to determine the relationship between urine DEHP metabolites and body composition (body measures, bioelectrical impedance analysis (BIA)). Results: After weighing the sampling strategy in multiple linear regression analysis, we report that higher levels of DEHP metabolites are correlated with increases in body measures (body weight, body mass index (BMI), waist circumference), BIA parameters (estimated fat mass, percent body fat, ECF, and ECF/intracellular fluid (ICF) ratio) in multiple linear regression analysis. The relationship between DEHP metabolites and the ECF/ICF ratio was more evident in subjects of younger age (20–39 years old), women, non-Hispanic white ethnicity, and subjects who were not active smokers. Conclusion: In addition to being positively correlated with body measures and body fat, we found that urine DEHP metabolites were positively correlated with ECF and the ECF/ICF ratio in the US general adult population. The finding implies that DEHP exposures might increase ECF volume and the ECF/ICF ratio, which may have adverse health outcomes on the cardiovascular system. Further research is needed to clarify the causal relationship.

7-DAYS HIGH-SALT DIET AFFECTS NO-MEDIATED MICROVASCULAR ENDOTHELIAL VASODILATION IN YOUNG HEALTHY INDIVIDUALS

Objective: We have previously reported that short-term (7-days) high-salt (HS) loading impairs microvascular endothelial function in young healthy individuals, independently of blood pressure (BP) or body composition and fluid status changes. This study aimed to functionally assess specifically nitric-oxide (NO) mediated endothelial vasodilation of skin microcirculation in response to 7-day HS diet in healthy salt-resistant individuals. Design and method: 20 young healthy individuals (10 women and 10 men), age ranged between 19–24 years, participated in the present study. All subjects adhered to a 7-day low-salt (LS) diet (3.5 g salt/day) followed by a 7-day high-salt (HS) diet (∼14.7 g salt/day) protocol. To confirm that subjects conformed to the diet protocol, daily salt intake based on 24-h urinary sodium excretion was calculated using appropriate formula before and after HS diet protocol. Blood pressure (BP) was measured before and after respective diet protocols and salt resistance was defined as a &lt; 5 mmHg change in mean arterial pressure (MAP) determined on LS versus HS diet. NO-mediated microvascular endothelial vasodilation in response to local heating (42°C) was functionally assessed using laser Doppler Flowmetry (LDF) (moorVMS-LDF, Moor Instruments, UK) and skin heater controller (moorVMS-HEAT, Moor Instruments, UK). Results: 24-hour sodium excretion significantly increased following HS diet compared to LS conditions (salt/g LS 6.6 ± 2.6 vs. HS 14.3 ± 2.5, P &lt; 0.001). Salt resistance was confirmed in all subjects undergoing study (MAP/mmHg LS 87 ± 7 vs. HS 86 ± 9, P = 0.829). 7-day HS diet significantly reduced skin microvascular flow increase in response to local heating compared to LS conditions (LDF HEAT LS 14.16 ± 6.01 vs. HS 10.67 ± 3.27, P = 0.006). Conclusions: Results of the present study have functionally demonstrated that 7-days HS diet alters specifically NO-mediated endothelium-dependent of skin microcirculation in salt-resistant young healthy individuals.

MO753: Marinobufagenin Predicts Intradialytic Hypotension Episodes in Prevalent Haemodialysis Patients

Abstract BACKGROUND AND AIMS Intradialytic hypotension (IDH) is a sudden and often dangerous complication of chronic haemodialysis (HD) treatment that may occur in ∼20%–30% of HD sessions. The pathogenesis of IDH is acknowledged to be multifactorial, as it might depend from an impaired vascular refilling capacity, excessive absolute fluid removal, an impaired sympathetic nerve response to volume loss or inadequate peripheral arterial vasoconstriction. This makes the prediction of IDH extremely challenging in the majority of cases. METHOD In this pilot, prospective study, we aimed at evaluating the clinical predictors of IDH in a small cohort of prevalent HD patients, with a particular focus on marinobufagenin (MBG), an endogenous cardiotonic steroid whose blood levels have previously been found notably altered in various cardiovascular disorders and body fluid status alterations. RESULTS MBG levels in HD patients were significantly higher than in controls (0.75 ± 0.29 versus 0.59 ± 0.19 nnmol/L; P = 0.03), remained unchanged throughout a single HD session and were not correlated with the absolute or partial fluid loss achieved. During a 30-day follow-up, 19 patients (65.5%) experienced at least one IDH (73 total episodes). An inverse correlation was found between baseline MBG and the number of IDH (R = –0.55; P = 0.001). HD patients experiencing IDH presented remarkably lower baseline MBG as compared with others (0.65 ± 0.28 versus 0.94 ± 0.21 nmol/L; P = 0.008) In these individuals, there was an apparent increase in MBG levels after the first hour of dialysis [0.72 (0.56–1.00) versus 0.65 ± 0.28 nmol/L; P = 0.04], while such levels progressively decreased throughout the rest of the session, being even more reduced at HD end as compared with baseline [0.45 (0.24–0.95) versus 0.65 ± 0.28 nmol/L; P = 0.04]. At Kaplan–Meier analyses, HD patients with lower MBG manifested a 4-fold to6-fold increased risk of IDH during follow-up (crude HR ranging from 4.37 to 6.68), depending on the time-point measurement of MBG. At Cox regression analyses, MBG measured at different time points resulted the strongest time-dependent predictor of IDH among all the variables considered (HR ranging from 0.068 to 0.155; P=0.002 to &amp;lt;0.0001). CONCLUSION Findings obtained suggest that altered MBG in prevalent HD patients may reflect a diverse vascular and haemodynamic tolerance to HD stress, eventually leading to recurrent IDH episodes. Further studies are needed to confirm the prognostic capacity of MBG for identifying HD patients at high risk of IDH, particularly those with apparently optimal fluid status.

Clinical Relevance of Body Fluid Volume Status in Diabetic Patients With Macular Edema.

ObjectiveTo investigate body fluid status in diabetic macular edema (DME) patients and the extent to which it is affected by renal function.MethodsOne hundred and thirty-two eyes from 132 patients with diabetes mellitus (DM) were prospectively collected in this cross-sectional, observational study. Thirty-five were DM patients without diabetic retinopathy (DR), 31 were DR patients without DME, and 66 were DME patients. The fluid status of each participant was quantified with extracellular water-to-total body water ratio (ECW/TBW) using a body composition monitor. Central subfield thickness (CST) and macular volume (MV) were obtained using optical coherence tomography (OCT). Urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and albumin was obtained using serum and urine laboratory data.ResultsECW/TBW was significantly increased in DME patients (39.2 ± 0.9, %) compared to DM (38.1 ± 0.7, %, P = 0.003) and DR patients without DME (38.7 ± 0.9, %, P < 0.001). In multilinear regression, fluid overload was positively related to DME and UACR (DME vs. DM: β = 2.418, P < 0.001; DME vs. DR: β = 1.641, P = 0.001; UACR, per 102, β = 1.017, P = 0.01). In the binary logistic regression for DME risk, the area under the receiver operating characteristic curve (AUROC) increased significantly by adding ECW/TBW along with UACR and age (AUC: 0.826 vs. 0.768).ConclusionDME patients had elevated body fluid volume independent of kidney functions. The assessment of extracellular fluid status may help in the management of DME.

Measurement of Caval Aorta Diameter Index by Transthoracic Echocardiogram in Normal Indian Population

Background: Bedside ultrasonography is a promising noninvasive and rapid technique to assess body fluid status. Early detection of hypovolemia and hypervolemia is crucial to guide management in critically ill patients. There is a considerable demographic variability in the normal range of inferior vena cava dimensions as seen in numerous studies and a steadfast formula to calculate caval diameter based on demographic parameters and body growth is not available till date. Caval aorta diameter index had a positive correlation with invasively measured central venous pressure as established by previous studies done in intensive care units. The simplicity of examination technique makes this index useful in every situation where body fluid status has therapeutic and prognostic implications. This study aims to identify standard normal measurement of caval aorta index by easily available two-dimensional echocardiography in subcostal view and by right coronal approach/transhepatic view in different age groups in Indian patients. Materials and Methods: One hundred and two patients referred for routine cardiac status evaluation who were asymptomatic and clinically normal without any major medical illness with normal echocardiogram were prospectively analyzed and caval aorta index assessed in both subxiphoid and transhepatic right coronal view. Results: Normal caval aorta index measured in subcostal view was 1.108 ± 0.076 and measured in transhepatic view was 1.101 ± 0.082 (mean ± 2 standard deviation). The difference of caval aorta index measured in both views was not significant statistically (P = 0.207). Conclusion: In this study, we provide a normal reference level for sonographic caval aorta index in Indian population measured in subxiphoid and transhepatic views. We also conclude that transhepatic right coronal view measurements for this index are comparable to subcostal view, so both views can be used alternatively when one window is suboptimal.