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Sodium/glucose cotransporter 2 and renoprotection: From the perspective of energy regulation and water conservation.
Kitada, K, Kidoguchi, S, Nakano, D, Nishiyama, A
Journal of pharmacological sciences. 2021;(3):245-250
Abstract
Sodium/glucose cotransporter 2 (SGLT2) is a renal low-affinity high-capacity sodium/glucose cotransporter expressed in the apical membrane of the early segment of proximal tubules. SGLT2 reabsorbs filtered glucose in the kidney, and its inhibitors represent a new class of oral medications used for type 2 diabetes mellitus, which act by increasing glucose and sodium excretion in urine, thereby reducing blood glucose levels. However, clinical trials showed marked improvement of renal outcomes, even in nondiabetic kidney diseases, although the underlying mechanism of this renoprotective effect is unclear. We showed that long-term excretion of salt by the kidneys, which predisposes to osmotic diuresis and water loss, induces a systemic body response for water conservation. The energy-intensive nature of water conservation leads to a reprioritization of systemic body energy metabolism. According to current data, use of SGLT2 inhibitors may result in similar reprioritization of energy metabolism to prevent dehydration. In this review article, we discuss the beneficial effects of SGLT2 inhibition from the perspective of energy metabolism and water conservation.
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Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet.
Gueneau de Mussy, P, Sidharta, PN, Wuerzner, G, Maillard, MP, Guérard, N, Iglarz, M, Flamion, B, Dingemanse, J, Burnier, M
Clinical pharmacology and therapeutics. 2021;(3):746-753
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Abstract
Aprocitentan is a novel, oral, dual endothelin receptor antagonist (ERA) in development in difficult-to-control hypertension. As fluid retention and edema are concerns with ERAs, we investigated whether aprocitentan causes weight gain in healthy subjects on a high sodium diet and explored potential mechanisms if occurring. This double-blind, randomized, placebo-controlled, crossover study enrolled 28 subjects. Three doses of aprocitentan (10, 25, or 50 mg/day for 9 days) were compared with placebo. Increases in body weight were observed with aprocitentan (placebo-corrected mean weight gains [90% confidence interval]) of 0.43 [0.05-0.80], 0.77 [0.03-1.51], and 0.83 [0.33-1.32] kg at 10 mg, 25 mg, and 50 mg, respectively. Decreases in hemoglobin and uric acid were observed. Plasma volume increased at most by 5.5% without dose-response relationship. Urinary sodium excretion decreased at 10 mg and 25 mg but not at 50 mg. Therefore, aprocitentan produced moderate weight increases in healthy subjects on high sodium diet, without obvious sodium retention.
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Total body water in full-term and preterm newborns: systematic review and meta-analysis.
Young, A, Brown, LK, Ennis, S, Beattie, RM, Johnson, MJ
Archives of disease in childhood. Fetal and neonatal edition. 2021;(5):542-548
Abstract
BACKGROUND Total body water (TBW) is one component of fat-free mass and changes in TBW are influenced by fluid shifts (especially during transition to postnatal life), electrolyte balance and nutritional status. Normal values for term-born neonates and preterm infants at birth have not been defined in large cohorts, limiting investigation into its monitoring and use in clinical practice. OBJECTIVE To systematically review the evidence base for percentage of TBW in term-born infants, quantify the effect of prematurity on TBW at birth, and describe normal progression of TBW over time in preterm infants. METHODS Systematic review of Medline, Web of Science Core Collection and EBSCO-CINAHL (January 1946 to January 2020). Included articles used dilutional methods to assess TBW. RESULTS Searches identified 2349 articles of which 22 included data suitable for analysis. Mean TBW in term-born newborns was 73.8% (95% CI 72.47% to 75.06%, 15 studies, 433 infants). Meta-regression showed that TBW was higher in preterm infants (up to 90% at 26 weeks gestation, dropping to 75% at 36 weeks corrected gestation) and was negatively correlated with gestation at birth, falling 1.44% per week (95% CI 0.63% to 2.24%, 9 studies, 179 infants). Analysis of TBW over time during the ex utero growth of preterm infants was not possible due to paucity of data. CONCLUSION This review defines the normal TBW percentage in term-born infants and confirms and quantifies previous findings that preterm infants have a higher TBW percentage.
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Extracellular water/total body water ratio as predictor of mortality in hemodialysis patients.
Pérez-Morales, R, Donate-Correa, J, Martín-Núñez, E, Pérez-Delgado, N, Ferri, C, López-Montes, A, Jiménez-Sosa, A, Navarro-González, JF
Renal failure. 2021;(1):821-829
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Abstract
BACKGROUND Overhydration is a predictor of mortality in hemodialysis (HD) patients. Bioimpedance spectroscopy (BIS) is used to determine the body composition. Extracellular Water/Total Body Water (ECW/TBW) ratio has been proposed to predict mortality. METHODS Multicenter, prospective, observational, proof-of-concept study to estimate the impact of ECW/TBW in global and cardiovascular mortality and the relationship with cardiovascular biomarkers. The study included 60 patients (mean age, 71.8 ± 11.4 years; mean time on HD, 52.3 ± 30.8 months) with a median follow-up of 30.5 months (IQ range, 17.2-34 months). RESULTS Post-dialysis ECW/TBW was directly associated with NT-proBNP and cTnT. During the study 28 patients died, most of them (43%) due to cardiovascular events. Compared to the survivors, these subjects had a higher post-dialysis ECW/TBW ratio (p = 0.006), while for cardiovascular mortality the only significant difference was a higher pre-dialysis ECW/TBW. The ability of post-dialysis ECW/TBW ratio to predict all-cause mortality had an area under the ROC curve (AUC) of 0.71 (CI 95%, 0.57-0.81; p = 0.002), with a cutoff point of 0.5023. For cardiovascular mortality the AUC was 0.66 (CI 95%, 0.52-0.77; p = 0.045), with a cutoff point of 0.4713. CONCLUSIONS The post-dialysis ECW/TBW ratio measured by BIS can be a predictor of all-cause and cardiovascular mortality.
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Effects of a 14-Day Hydration Intervention on Individuals with Habitually Low Fluid Intake.
Caldwell, AR, Rosa-Caldwell, ME, Keeter, C, Johnson, EC, Péronnet, F, Ganio, MS
Annals of nutrition & metabolism. 2020;:67-68
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Abstract
BACKGROUND Debate continues over whether or not individuals with low total water intake (TWI) are in a chronic fluid deficit (i.e., low total body water) [1]. When women with habitually low TWI (1.6 ± 0.5 L/day) increased their fluid intake (3.5 ± 0.1 L/day) for 4 days 24-h urine osmolality decreased, but there was no change in body weight, a proxy for total body water (TBW) [2]. In a small (n = 5) study of adult men, there were no observable changes in TBW, as measured by bioelectrical impedance, after increasing TWI for 4 weeks [3]. However, body weight increased and salivary osmolality decreased indicating that the study may have been underpowered to detect changes in TBW. Further, no studies to date have measured changes in blood volume (BV) when TWI is increased. OBJECTIVES Therefore, the purpose of this study was to identify individuals with habitually low fluid intake and determine if increasing TWI, for 14 days, resulted in changes in TBW or BV. METHODS In order to identify individuals with low TWI, 889 healthy adults were screened. Participants with a self-reported TWI less than 1.8 L/day (men) or 1.2 L/day (women), and a 24-h urine osmolality greater than 800 mOsm were included in the intervention phase of the study. For the intervention phase, 15 participants were assigned to the experimental group and 8 participants were assigned to the control group. The intervention period lasted for 14 days and consisted of 2 visits to our laboratory: one before the intervention (baseline) and 14 days into the intervention (14-day follow-up). At these visits, BV was measured using a CO-rebreathe procedure and deuterium oxide (D2O) was administered to measure TBW. Urine samples were collected immediately prior, and 3-8 h after the D2O dose to allow for equilibration. Prior to each visit, participants collected 24-h urine to measure 24-h hydration status. After the baseline visit, the experimental group increased their TWI to 3.7 L for males and 2.7 L for females in order to meet the current Institute of Medicine recommendations for TWI. RESULTS Twenty-four-hour urine osmolality decreased (-438.7 ± 362.1 mOsm; p < 0.001) and urine volume increased (1,526 ± 869 mL; p < 0.001) in the experimental group from baseline, while there were no differences in osmolality (-74.7 ± 572 mOsm; p = 0.45), or urine volume (-32 ± 1,376 mL; p = 0.89) in the control group. However, there were no changes in BV (Fig. 1a) or changes in TBW (Fig. 1b) in either group. CONCLUSIONS Increasing fluid intake in individuals with habitually low TWI increases 24-h urine volume and decreases urine osmolality but does not result in changes in TBW or BV. These findings are in agreement with previous work indicating that TWI interventions lasting 3 days [2] to 4 weeks [3] do not result in changes in TBW. Current evidence would suggest that the benefits of increasing TWI are not related changes in TBW.
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Peripheral Intrastromal Hydration Facilitates Safe, Deep Trephination in Corneas of Irregular Thickness.
Bovone, C, Myerscough, J, Friehmann, A, Elkadim, M, Parmeggiani, F, Busin, M
Cornea. 2020;(2):207-209
Abstract
PURPOSE To evaluate the feasibility of regularizing the peripheral corneal thickness before deep trephination in highly irregular corneas undergoing deep anterior lamellar keratoplasty (DALK) by means of intrastromal hydration with saline. METHODS This is an interventional case series including all eyes with irregular peripheral corneal thickness undergoing DALK for any indication between January 1, 2016, and January 1, 2017, at a single tertiary center in Forli, Italy. Before trephination, 1 mL of normal saline was injected intrastromally into each clock hour of peripheral thinning (determined using preoperative pachymetry) using a 30-gauge needle. A deep trephination of 400 to 450 μm was then performed, and DALK was completed as per our previously described technique. Primary outcome measures were perforation during trephination and intraoperative complications, with secondary outcomes of best corrected visual acuity and refraction. RESULTS Peripheral intrastromal hydration was performed in 61 eyes of 61 patients. Intrastromal hydration ensured a safe trephination without perforation into the anterior chamber (AC) in 59 of 61 eyes. In the 2 cases in which perforation occurred, the perforation site was sutured with a full-thickness suture and the surgery was completed successfully. No cases required conversion to penetrating keratoplasty. Intrastromal injection of 1 mL of normal saline resulted in an increase in corneal thickness of 31%. After surgery, double AC was observed in 3 cases (4.9%), with all cases being managed successfully by air injection into the AC. CONCLUSIONS Zonal peripheral intrastromal hydration is a feasible technique to enable safe, deep trephination even in corneas of highly irregular thickness.
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Reviewing the current methods of assessing hydration in athletes.
Barley, OR, Chapman, DW, Abbiss, CR
Journal of the International Society of Sports Nutrition. 2020;(1):52
Abstract
BACKGROUND Despite a substantial body of research, no clear best practice guidelines exist for the assessment of hydration in athletes. Body water is stored in and shifted between different sites throughout the body complicating hydration assessment. This review seeks to highlight the unique strengths and limitations of various hydration assessment methods described in the literature as well as providing best practice guidelines. MAIN BODY There is a plethora of methods that range in validity and reliability, including complicated and invasive methods (i.e. neutron activation analysis and stable isotope dilution), to moderately invasive blood, urine and salivary variables, progressing to non-invasive metrics such as tear osmolality, body mass, bioimpedance analysis, and sensation of thirst. Any single assessment of hydration status is problematic. Instead, the recommended approach is to use a combination, which have complementary strengths, which increase accuracy and validity. If methods such as salivary variables, urine colour, vital signs and sensation of thirst are utilised in isolation, great care must be taken due to their lack of sensitivity, reliability and/or accuracy. Detailed assessments such as neutron activation and stable isotope dilution analysis are highly accurate but expensive, with significant time delays due to data analysis providing little potential for immediate action. While alternative variables such as hormonal and electrolyte concentration, bioimpedance and tear osmolality require further research to determine their validity and reliability before inclusion into any test battery. CONCLUSION To improve best practice additional comprehensive research is required to further the scientific understanding of evaluating hydration status.
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Safety and Efficacy of Oral Intake of Ceramide-Containing Acetic Acid Bacteria for Improving the Stratum Corneum Hydration: A Randomized, Double-Blind, Placebo-Controlled Study over 12 Weeks.
Tsuchiya, Y, Ban, M, Kishi, M, Ono, T, Masaki, H
Journal of oleo science. 2020;(11):1497-1508
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Abstract
The barrier function of the skin protects it from external stresses to which it is constantly exposed, such as dryness, ultraviolet rays, and chemicals. Lipids, in particular a type of sphingolipid known as ceramides, play a central role in the barrier function of the skin by preventing dryness. The number of ceramides in the skin is known to decrease with age, which has led to the development of a large number of anti-aging cosmetic products that contain ceramides. Recently, it has become evident that oral intake of ceramides can also improve the quality of the skin. To elucidate the effects of oral ceramide intake on skin moisture content, we conducted a randomized, double-blinded, placebo-controlled parallel comparative study in which males and females between 20 and 60 years of age who were worried about dry skin ingested a food with acetic acid bacteria containing 0.8 mg of dihydroceramide or a placebo for 12 weeks. Concurrently, we investigated the safety of continuous ingestion of the ceramide-containing food over 12 weeks. Oral intake of ceramide over the 12 weeks significantly improved stratum corneum hydration, i.e. the moisture content of the skin, and did not result in harmful effects in any of the participants.
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Effect of Increased Daily Water Intake and Hydration on Health in Japanese Adults.
Nakamura, Y, Watanabe, H, Tanaka, A, Yasui, M, Nishihira, J, Murayama, N
Nutrients. 2020;(4)
Abstract
Increased hydration is recommended as healthy habit with several merits. However, supportive data are sparse. To assess the efficacy of increased daily water intake, we tested the effect of water supplementation on biomarkers in blood, urine, and saliva. Twenty-four healthy Japanese men and 31 healthy Japanese women with fasting blood glucose levels ranging from 90-125 mg/dL were included. An open-label, two-arm, randomized controlled trial was conducted for 12 weeks. Two additional 550 mL bottles of water on top of habitual fluid intake were consumed in the intervention group. The subjects drank one bottle of water (550 mL) within 2 h of waking, and one bottle (550 mL) 2 h before bedtime. Subjects increased mean fluid intake from 1.3 L/day to 2.0 L/day, without changes in total energy intake. Total body water rate increased with associated water supplementation. There were no significant changes in fasting blood glucose and arginine vasopressin levels, but systolic blood pressure was significantly decreased in the intervention group. Furthermore, water supplementation increased body temperature, reduced blood urea nitrogen concentration, and suppressed estimated glomerular filtration rate reduction. Additionally, existence of an intestinal microbiome correlated with decreased systolic blood pressure and increased body temperature. Habitual water supplementation after waking up and before bedtime in healthy subjects with slightly elevated fasting blood glucose levels is not effective in lowering these levels. However, it represents a safe and promising intervention with the potential for lowering blood pressure, increasing body temperature, diluting blood waste materials, and protecting kidney function. Thus, increasing daily water intake could provide several health benefits.
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Body hydration assessment using bioelectrical impedance vector analysis in neurologically impaired children.
Calcaterra, V, Cena, H, Manuelli, M, Sacchi, L, Girgenti, V, Larizza, C, Pelizzo, G
European journal of clinical nutrition. 2019;(12):1649-1652
Abstract
Dehydration is common and frequently under-diagnosed in chronic malnourished children, leading to life-threatening conditions. In this pilot study we applied bioimpedance vector analysis (BIVA) to determine hydration status in 52 neurologically impaired (NI) paediatric patients (14.08 ± 5.32). Clinical and biochemical data were used to define malnutrition and dehydration. Body composition analysis and hydration were also assessed by BIVA and we considered 143 normal-weight healthy subjects (15.0 ± 1.7), as controls for hydration status assessment. BIVA revealed a pathological hydration status in NI children, showing higher resistance (p < 0.001) and reactance values (p = 0.001) compared to controls. No differences in reactance and resistance were detected between well-nourished and under-nourished subjects. Four patients out of 52 showed mild signs of dehydration; no severe dehydration was detected. Laboratory data, suggestive for dehydration, were similar in well-nourished and under-nourished NI subjects. In conclusion, in our sample of NI paediatrics, dehydration according to clinical signs and laboratory data was under-diagnosed. BIVA showed specific bioelectrical characteristics that could be compatible with impaired hydration status. Further studies are necessary to confirm that BIVA may an applicable tool for defining dehydration status and guiding rehydration in NI children.