Urinary Sodium Excretion Rate Research Articles

Assessment and Management of Patients with Obesity and Hypertension in European Society of Hypertension Excellence Centres. A survey from the ESH Working Group on Diabetes and Metabolic Risk Factors.

Healthcare providers are faced with an increasing number of patients with obesity and arterial hypertension. Preventing obesity-associated hypertension and appropriately managing patients with established disease are both important. Hence, the aim of our study was to evaluate the clinical care of patients with obesity and hypertension among ESH Excellence Centres (ECs). We conducted a cross-sectional, international 30-item survey through e-mails. In total, 70 representatives of ECs participated (78% men) with 66% of them practicing medicine for more than 30 years and working in well-equipped clinics. Most were internists (41%) and cardiologists (37%) and 73% reported training on the management of obese patients with hypertension. A majority weigh their patients (77%) and evaluate patients for sleep disorders (93%). However, only 47% spend more than 5min to advise for lifestyle modification in general, 59% for weight loss, 56% for salt intake and 64% for exercise. Finally, a minority of participants ask patients if they like their body (6%) or about previous attempts to lose weight (28%), evaluate 24h urinary sodium excretion rate (22%) and provide written (15%) or personalized (10%) dietary advices. If the patient suffers also from type 2 diabetes mellitus, 66% switch treatment to GLP1 receptor agonists and 60% to SGLT2 inhibitors. Most clinicians in ESH ECs are well educated regarding obesity-associated hypertension, and clinics are sufficiently equipped to manage these patients, as well. However, several deficits were reported regarding efforts to address and implement obesity specific aspects and interventions to improve care in patients with obesity and hypertension.

Effect of GRK4 on renal gastrin receptor regulation in hypertension

ABSTRACT Objective To investigate whether GRK4 regulates the phosphorylation and function of renal CCKBR. Methods GRK4 A142V transgenic mice were used as an animal model of enhanced GRK4 activity, and siRNA was used to silence the GRK4 gene to investigate the regulatory effect of GRK4 on CCKBR phosphorylation and function. Finally, the co-localization and co-connection of GRK4 and CCKBR in RPT cells were observed by laser confocal microscopy and immunoprecipitation to explore the mechanism of GRK4 regulating CCKBR. Results Gastrin infusion significantly increased urinary flow and sodium excretion rates in GRK4 WT mice (P < .05). GRK4 siRNA did not affect CCKBR protein expression in WKY RPT cells and SHR RPT cells, but remarkably reduced CCKBR phosphorylation in WKY and SHR RPT cells (P < .05). The inhibitory effect of gastrin on Na+-K+ -ATPase activity in WKY RPT cells was further enhanced by the reduction of GRK4 expression (P < .05), while GRK4 siRNA restored the inhibitory effect of gastrin on Na+-K+ -ATPase activity in SHR RPT cells. Laser confocal and Co-immunoprecipitation results showed that GRK4 and CCKBR co-localized in cultured RPT cells’ cytoplasm. Conclusion GRK4 participates in the development of hypertension by regulating the phosphorylation of renal CCKBR leading to impaired CCKBR function and water and sodium retention. Knockdown of GRK4 restored the function of CCKBR. The enhanced co-connection between GRK4 and CCKBR may be an important reason for the hyperphosphorylation of GRK4 and CCKBR involved in the pathogenesis of hypertension.

Effects of lipopolysaccharide stimulation during pregnancy on kidneys and blood vessels in offspring rats

Objective: To investigate the effect of lipopolysaccharide (LPS) inflammatory stimulation during pregnancy on offspring rats. Methods 20 SD pregnant rats were randomly divided into control and LPS groups, with 10 rats in each group. Rats in LPS group received intraperitoneal injection of LPS 0.79 mg/kg on the Days 8th, 10th, and 12th of gestation, and rats in control group received intraperitoneal injection of the same volume of sterile saline. The blood pressure of offspring rats was measured once every two weeks from 8 weeks of age to 16 weeks of age. Protein expression of NF-κB and NOX2 was detected by immunohistochemistry. ROS and NO levels in vascular tissues were observed by staining with DHE and DAF-2DA cular tissues were observed by staining with DHE and DAF-2DA fluorescent probes, respectively. Results At 8, 10, 12, 14 and 16 weeks of age,the systolic blood pressure of offspring in the LPS group was higher than that of the control group at the same age (P< 0.01).The urine volume and urinary sodium excretion rate of the LPS group were significantly lower than those of the control group (P < 0.05), while the urine creatinine and urine protein were not statistically significant as compared with those of the control group. Compared with the control group, the expression of NF-κB, NOX2, Ang II in thoracic aorta, and ROS in mesenteric artery were higher in LPS group. However, mesenteric artery NO expression was lower (P < 0.01) Conclusion LPS inflammatory stimulation during pregnancy causes kidneys inflammation and increased oxidative stress in blood vessels in offspring rats.

Torsemide Pharmacometrics in Healthy Adult Populations Including CYP2C9 Genetic Polymorphisms and Various Patient Groups through Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling.

Torsemide is a widely used diuretic in clinical practice. In this study, pharmacokinetic (PK) and pharmacodynamic (PD) simulations of torsemide for various population groups and exposure scenarios were performed through human-scale physiologically-based PK-PD (PBPK-PD) modeling of torsemide. For PBPK-PD modeling of torsemide, invitro and clinical data of torsemide reported previously were used. After exposure to clinical doses of torsemide, observed plasma (or serum) concentration and urine torsemide excretion profiles were used as PK-data, and observed urinary sodium excretion rate was used as PD-data. The model was then extended to take into account physiological and biochemical factors according to different CYP2C9 phenotypes or patient populations. The established model captured various torsemide clinical results well. Differences in torsemide PKs and PDs between patient groups or CYP2C9 genetic polymorphisms were modelologically identified. It was confirmed that degrees of differences in torsemide PKs and PDs by disease groups were greater than those according to different CYP2C9 phenotypes. According to torsemide administration frequency or dose change, it was confirmed that although the difference in plasma PKs between groups (healthy adult and patient groups) could increase to 14.80 times, the difference in PDs was reduced to 1.01 times. Results of this study suggested that it is very important to consider disease groups in the setting of torsemide clinical therapy and that it is difficult to predict PD proportionally with only differences in PKs of torsemide between population groups. The PBPK-PD model established in this study is expected to be utilized for various clinical cases involving torsemide application in the future, enabling optimal drug therapy.

RHO KINASE BLOCKADE ALLEVIATE BLOOD PRESSURE ELEVATION AND INHIBIT VASCULAR REMODELING IN APATINIB-INDUCED HYPERTENSION–TO BE CONFERMED

Objective: Hypertension and kidney injury are two of the major adverse effects of the targeted anti-tumor drug apatinib, it was suspected that hypertension may be the result of renal dysfunction in some of the previous studies. The present study was designed to explore the different responses of blood pressure and kidney in the apatinib-induced hypertensive rat model. Design and method: 30 Wistar-Kyoto rat were randomly divided into 3 groups, each group was administered with 2 mL 0.9% saline, 30 mg/d of apatinib or 15 mg/d of apatinib by oral gavage for 2 weeks. Blood pressure was monitored at the baseline and during the treatment. Level of creatinine, urea nitrogen, sodium, albumin and protein in blood and urine were tested both at baseline and at the end of the treatment. Urinary sodium excretion and glomerular filtration rate was calculated. Specific mRNA and proteins were detected at the end of the treatment. Results: Average mean blood pressure (MBP) in the high dose apatinib group was 105 mmHg at the 9th day and 113 mmHg at the 15th day, average MBP in the low dose apatinib was 98 mmHg at the 9th day and 108 mmHg at the 15th day. MBP were significantly high in apatinib group, no matter in the high dose or low dose (p &lt; 0.01). Compared with the control group, the level of endothelin 1(ET-1) and college-1 were significantly high in both apatinib group (p &lt; 0.01). There was no significant differences of urinary sodium excretion, glomerular filtration rate and microalbuminuria between the control group and the low dose apatinib group, while that in the high dose apatinib group were significantly high (p &lt; 0.01). Conclusions: There are differences in the response to different doses of apatinib between blood pressure and kidney, blood pressure was elevated even at a relevantly lower dose of apatinib, which was accompanied with the elevation of ET-1 level and vascular emodelling, while the kidney injury occurred only at higher dose of apatinib. The hypertension induced by apatinib was independent with kidney injury caused by the drug, not the consequence of it.

A multiple 24-hour urine collection study indicates that kidney function decline is related to urinary sodium and potassium excretion in patients with chronic kidney disease

Multiple 24-hour urine collections are necessary to adequately assess sodium and potassium intake. Here, we assessed kidney function decline for four years after baseline in relation to seven-time averaged 24-hour urinary sodium and potassium excretion (UNaV, UKV), their UNaV/UKV ratio, and their categorical combination in outpatients with chronic kidney disease (CKD). This retrospective cohort study was based on 240 outpatients with baseline CKD stages 3-5, baseline age 20 years or more (median age 72.0 years), and a median follow-up (with interquartile range) of 2.9 (1.4-4.0) years. Outcome was the percentage change in annual slope of estimated glomerular filtration rate (delta eGFR per year). In linear mixed models, percentage changes in delta eGFR per year were -3.26% (95% confidence interval -5.85 to -0.60),+5.20% (2.34 to 8.14), and -5.20% (-7.64 to -2.69), respectively, per one standard deviation increase in the seven-time averaged UNaV and UKV, and their UNaV/UKV ratio. Additionally, percentage changes per year in delta eGFR per year were -16.27% (-23.57 to -8.27) in the middle-to-high UNaV and low UKV group, compared with the low UNaV and middle-to high UKV group. Thus, our study reinforces the observation of opposite associations between GFR decline and urinary excretion rates of sodium (positive) and potassium (negative), respectively. Whether changes in dietary sodium and potassium intake slow GFR decline still requires further study.

Salt-Sensitive Hypertension, Renal Injury, and Renal Vasodysfunction Associated With Dahl Salt-Sensitive Rats Are Abolished in Consomic SS.BN1 Rats.

BackgroundAbnormal renal hemodynamic responses to salt‐loading are thought to contribute to salt‐sensitive (SS) hypertension. However, this is based largely on studies in anesthetized animals, and little data are available in conscious SS and salt‐resistant rats.Methods and ResultsWe assessed arterial blood pressure, renal function, and renal blood flow during administration of a 0.4% NaCl and a high‐salt (4.0% NaCl) diet in conscious, chronically instrumented 10‐ to 14‐week‐old Dahl SS and consomic SS rats in which chromosome 1 from the salt‐resistant Brown‐Norway strain was introgressed into the genome of the SS strain (SS.BN1). Three weeks of high salt intake significantly increased blood pressure (20%) and exacerbated renal injury in SS rats. In contrast, the increase in blood pressure (5%) was similarly attenuated in Brown‐Norway and SS.BN1 rats, and both strains were completely protected against renal injury. In SS.BN1 rats, 1 week of high salt intake was associated with a significant decrease in renal vascular resistance (−8%) and increase in renal blood flow (15%). In contrast, renal vascular resistance failed to decrease, and renal blood flow remained unchanged in SS rats during high salt intake. Finally, urinary sodium excretion and glomerular filtration rate were similar between SS and SS.BN1 rats during 0.4% NaCl and high salt intake.ConclusionsOur data support the concept that renal vasodysfunction contributes to blood pressure salt sensitivity in Dahl SS rats, and that genes on rat chromosome 1 play a major role in modulating renal hemodynamic responses to salt loading and salt‐induced hypertension.

VERIFY AND EVALUATE FOUR SPOT URINARY METHODS FOR ESTIMATING 24-HOUR URINARY SODIUM EXCRETION RATE IN TIBETAN POPULATION

Objective: To verify and evaluate four spot urinary methods for estimating 24-hour urinary sodium excretion rate in Tibetan population (Kawasaki method, Tanaka method, INTERSALT method and SH2 method). Design and method: 323 subjects were selected from the Ganzi Tibetan Autonomous Prefecture of Sichuan Province, China. The morning second urine samples and 24 hours urine samples were collected. The concentrations of creatinine, sodium and potassium in the morning second urine samples and 24 hours urine samples were measured. To compare the mean deviation, correlation, and consistency between the measured values and estimated 24-hour urinary sodium excretion by Kawasaki method, Tanaka method, INTERSALT method and SH2 method. Results: The average differences between the estimated values and measured values by Kawasaki method, Tanaka method, INTERSALT method and SH2 method were 124.86 mg/days, -937.58 mg/days, -1314.15 mg/days and -1747.436 mg/days, respectively. The correlation coefficient with the measured values was 0.434, 0.38, 0.273 and 0.348, respectively. The intraclass correlation coefficient was higher for Kawasaki method (0.473) than for Tanaka method (0.397), INTERSALT method (0.269) and SH2 method (0.348). The Bland Altman analysis showed 3.4%, 6.2%, 5.9% and 5.6% of the subjects’ estimated values exceeded the consistent boundary of ± 1.96 for Kawasaki method, Tanaka method, INTERSALT method and SH2 method. When four spot urinary sodium methods used for evaluating the individual salt intake, the misclassification rate was more than 45%. Compared with the other three methods, the misclassification probability of Kawasaki method was 48.2%, while the misclassification probability of Tanaka, INTERSALT and SH2 methods was 72.1%, 75.5% and 74.6%, respectively. However, when individual's salt intake was higher than 12.8 g/days, the probability of misclassification of Kawasaki method, Tanaka method, INTERSALT method and SH2 method was 20%, 90%, 97.5% and 97.5%, respectively. Conclusions: When the Kawasaki method is used to evaluate the salt intake of Tibetan population, the deviation, consistency and reproducibility were better than Tanaka method, INTERSALT method and SH2 method. It was especially suitable for the evaluation of 24-hour urinary sodium excretion rate of people with high salt intake. It can be used to investigate the salt intake of Tibetan population in a large-scale epidemiological study.

Food Literacy Is Associated With Adherence to a Mediterranean-Style Diet in Kidney Transplant Recipients

Adherence to a Mediterranean-style diet is associated with improved health outcomes in kidney transplant recipients (KTR). However, poor dietary habits, including excessive sodium intake, are common in KTR, indicating difficulties with incorporating a healthy diet into daily life. Food literacy is identified as potential facilitator of a healthy diet, but the precise relationship between food literacy and dietary intake in KTR has not been investigated. This study examined food literacy levels in KTR and its association with adherence to a Mediterranean-style diet and sodium intake. This cross-sectional study is part of the TransplantLines Cohort and Biobank Study. Food literacy was measured with the Self-Perceived Food Literacy (SPFL) questionnaire. Dietary intake assessment with food frequency questionnaires was used to calculate the Mediterranean Diet Score. Sodium intake was based on the 24-hour urinary sodium excretion rate. Associations of SPFL with Mediterranean Diet Score and sodium intake were assessed with univariable and multivariable linear regression analyses. In total, 148 KTR (age 56 [48-66]; 56% male) completed the SPFL questionnaire with a mean SPFL score of 3.63±0.44. Higher SPFL was associated with a higher Mediterranean Diet Score in KTR (β = 1.51, 95% confidence interval 0.88-2.12, P ≤ .001). Although KTR with higher food literacy tended to have a lower sodium intake than those with lower food literacy (P=.08), the association of food literacy with sodium intake was not significant in a multivariable regression analysis (β= 0.52 per 10mmol/24-hour increment, 95% confidence interval -1.79 to 2.83, P=.66). Higher levels of food literacy are associated with better adherence to a Mediterranean-style diet in KTR. No association between food literacy and sodium intake was found. Further studies are needed to determine if interventions on improving food literacy contribute to a healthier diet and better long-term outcomes in KTR.

Abstract P2035: Severity of Hypertension Due to Elastin Haploinsufficiency is Sex-Dependent

William syndrome, an autosomal-dominant disease, is caused partly by loss-of-function mutations or gene macro-deletions resulting in elastin ( Eln ) haploinsufficiency. A major hallmark of Eln haploinsufficiency is hypertension, accompanied by arteriopathy and tortuous and elongated vessels. Previously, we showed that hypertension due to Eln haploinsufficiency in mice is due at least partly to abnormal remodeling of renal vascular signaling and increased blood pressure sensitivity to dietary salt observed only in male Eln +/- mice. In this study, we tested the hypothesis that ovarian hormones protect against excessive blood pressure increase resulting from Eln haploinsufficiency and blood pressure sensitivity to dietary salt in female mice. We used radiotelemetry to acquire diurnal blood pressure (BP) and heart rate (HR) before and after oophorectomy (OVX) in female wild type and Eln +/- mice. Four weeks after OVX, mice were placed on normal or high salt diet for 10 days, with continual acquisition of telemetry BP and HR. We assessed renal function by measuring urinary excretion of creatinine, sodium and potassium. Expression of sodium transporters was assessed by Western blot. Prior to OVX, baseline BP was elevated in Eln +/- mice (WT: 114 ± 3 vs. Eln +/- : 128 ± 8 mmHg; p =0.08). This was accompanied by a marked decrease in sodium/chloride co-transporter activity (phospho-NCC) and total-NCC in Eln +/- kidneys and a trend towards increased expression of epithelial sodium channel (ENaC)-alpha and beta isoforms, and decreased trend in overnight urinary sodium excretion rate (WT: 579 ± 95 vs. Eln +/- : 439 ± 82 μmol/h/g KW). Four weeks after OVX, BP was further elevated in Eln +/- mice (WT: 119 ± 7 vs. Eln +/- : 151 ± 10 mmHg; p &lt;0.01) but was not further elevated by chronic high-salt diet (OVX + NS Eln +/- : 151 ± 10 vs. OVX + HS Eln +/- : 131 ± 5 mmHg; p =0.12). OVX also caused a robust increase in ENaC expression in Eln +/- kidneys, whereas the same effect was seen in WT kidneys only after OVX plus high salt diet. We conclude that ovarian hormones suppress blood pressure elevation attributed to Eln haploinsufficiency and protect against blood pressure sensitivity to increased dietary sodium consumption.

Effects of Melamine and Cyanuric Acid on Renal Function and Structure in Rats

Melamine has been used to increase the amount of measurable nitrogen which is a component of protein. The renal toxicity of melamine has been reported in infants and animals that consumed a mixture of melamine in their food products. This study aimed to investigate the effects of melamine on rat renal function using clearance and histological techniques. Animals were divided into 3 groups: vehicle control, 400 mg/kg melamine and mixture of 400 mg/kg melamine and 400 mg/kg cyanuric acid (p.o., daily for three days). The results showed that blood urea nitrogen level significantly increased in the rats treated with the mixture of melamine and cyanuric acid. The urine flow rate, glomerular filtration rate, renal plasma flow and urinary sodium and potassium excretion rate significantly decreased when compared to vehicle control. These results suggested both glomeruli and renal tubules of rats treated with mixture of melamine and cyanuric acid were damaged. Histological study also confirmed these findings and showed significant glomerular atrophy and dilated renal tubules. Numerous clear brownish-yellow crystals were also found in the distal tubule, collecting tubule and papillary duct. However, rats solely treated with melamine showed no significant difference in renal function or structures.

Impact of oxidative stress on renal dopamine D(1) receptor dysfunction in offspring of diabetic rat dams

Objective: To explore the effects of oxidative stress on renal dopamine D(1) receptor dysfunction in offspring of diabetic rat dams. Methods: The pregnant Sprague Dawley (SD) rats (n=10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (n=5 each group). The offspring rats were divided into 4 groups including offspring of control dams treated with vehicle, offspring of control dams treated with antioxidant, offspring of diabetic dams treated with vehicle and offspring of diabetic dams treated with antioxidant (n=10 each group). After birth, the offspring rats were treated with normal drinking water or antioxidant (tempol, 1.0 mmol/L) from the age of 4 weeks until the end of the study (20 weeks). The blood pressure was monitored continuously by non-invasive tail-cuff method. The renal oxidative markers including superoxide dismutase (SOD) and malondialdehyde (MDA) activity and D(1) receptor agonist (fenoldopam)-mediated urinary and sodium excretion were detected. Furthermore, the protein expression of renal G protein-coupled receptor kinase 2 (GRK2), GRK4, dopamine D(1) receptor and the phosphorylation level of D(1) receptor were detected. Results: The mean arterial pressure of offspring from the diabetic dams treated with vehicle was significantly higher than that of offspring from control dams treated with vehicle (P=0.013), while the mean arterial pressure of offspring from diabetic dams treated with antioxidant was significantly lower than that of offspring from the diabetic dams treated with vehicle (P=0.038). The fenoldopam-mediated urinary flow and urinary sodium excretion rate were significantly lower in offspring of diabetic dams treated with vehicle than those in offspring of control dams treated with vehicle (P<0.01), which were significantly higher in offspring of diabetic dams treated with antioxidant as compared to offspring of diabetic dams treated with vehicle (both P<0.01). There was no significant difference in fenoldopam-mediated urinary flow and urinary sodium excretion rate in offspring of control dams treated with antioxidant or vehicle (urinary flow: P=0.772; urinary sodium excretion rate: P=0.716). Compared with offspring of control dams treated with vehicle, the renal MDA activity was significantly increased, while the SOD activity was significantly decreased in offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.013). The renal MDA activity was significantly decreased, while the SOD activity was significantly increased in offspring of diabetic dams treated with antioxidant in comparison with offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.035).The renal GRK2 and GRK4 protein expression in offspring of diabetic dams treated with vehicle were significantly higher than those in offspring of control dams treated with vehicle (P<0.01), while the expression levels of renal GRK2 and GRK4 in offspring of diabetic dams treated with antioxidant were significantly downregulated compared with offspring of diabetic dams treated with vehicle (P<0.01). There was no significant difference in the protein expression of dopamine D(1) receptor among 4 groups (P=0.735). The level of dopamine D(1) receptor phosphorylation in offspring of diabetic dams treated with vehicle was significantly higher than that in offspring of control dams treated with vehicle (P<0.01), while the dopamine D(1) receptor phosphorylation level was significantly lower in offspring of diabetic dams treated with antioxidant compared to that in offspring of diabetic dams treated with vehicle (P<0.01). Conclusion: Oxidative stress is involved in the dopamine D(1) receptors dysfunction in the offspring of diabetic dams.

THE ROLE OF HIGH DIETARY SALT INTAKE IN DEVELOPMENT OF RESISTANT HYPERTENSION

Objective: Aim of the study: evaluate salt-taste sensitivity and daily salt intake in patients with resistant arterial hypertension (RAH) during antihypertensive treatment (AHT). Design and method: The study included 137 patients with high risk arterial hypertension in average age 56.6 ± 9.8 years. All patients took triple combination AHT with diuretic, RAAS-blocker and calcium antagonists during 3 months. After 3 months therapy 83.2% patients were achieved goal BP, 16.8% of them were resistant to triple combination AHT. Thus, patients divided into 2 groups: RAH (n = 23) and non-RAH (n = 114) and continued AHT with recommendation to reduce dietary salt intake to 5–6 g/24 h. Salt-taste sensitivity (STS) evaluation, implemented R.Henkin method with using sodium chloride in different concentration: from 0.01% to 1.28%. The patients divided to 3 STS thresholds: low (0.01%-0.08% NaCl), medium (0.16% NaCl), and high thresholds (>0.32% NaCl). Daily salt intake was calculated by urinary sodium excretion level multiply 2.55, before and after treatment. Results: Patients with RAH characterized with significantly high systolic and diastolic BP (SBP/DBP): 178.1 ± 15.4/103.3 ± 10.1 mmHg vs. 158.9 ± 13.3/98.7 ± 7.25 mmHg in non-RAH group (p = 0.0001). STS test was shown prevalence high threshold of STS in RAH patients (high/medium 90.5%/9.5% χ2 = 46.7, p = 0.0001) in comparison with non-RAH group (high/medium/low 74%/12%/14% χ2 = 130.4, p = 0.0001) with significant difference in sodium chloride concentration: 0.41 ± 0.17% vs. 0.3 ± 0.18%, p = 0.01, for RAH and non-RAH groups respectively. Before AHT daily urinary sodium excretion rate was high in RAH patients (5.66 ± 2.49 g/24 h vs. 4.5 ± 2.54 g/24 h, p = 0.056), that corresponded to 14.4 g and 11.47 g daily salt intake in RAH and non-RAH respectively. During 6 months therapy BP significantly decreased in both groups, but in non-RAH group BP reducing was better with statistical difference: 128.3 ± 11.46/80.8 ± 7.9 mmHg vs. 122.4 ± 6.0/76.36 ± 8.5 mmHg, p = 0.0001 and p = 0.022 for SBP and DBP respectively. Daily urinary sodium excretion rate was significantly decreased only in non-RAH patients in comparison with RAH patients with statistical difference: 3.8 ± 2.29 g/24 h vs. 5.46 ± 2.7 g/24 h (p = 0.006). Conclusions: Patients with RAH characterized with high STS threshold and dietary salt intake. During six monthly optimal AHT, BP significantly reducing in both groups, but in non-RAH patients BP and daily urinary sodium excretion was statistically lower.

Urine 24-Hour Sodium Excretion Decreased between 1953 and 2014 in Japan, but Estimated Intake Still Exceeds the WHO Recommendation

Background: Accurate monitoring of sodium intake is necessary for evaluating strategies used to reduce sodium intake. However, no repeat survey has been conducted in representative populations in Japan to examine trends in sodium intake with the use of 24-h urinary sodium excretion, a standard evaluation method for sodium intake monitoring.Objective: The objective of this study was to examine potential trends in sodium intake by examining previous reports of 24-h urinary sodium excretion in healthy Japanese adult populations.Methods: We systematically searched for reports of 24-h urinary sodium excretion in healthy Japanese adult populations (mean age range: 18-69 y). We searched PubMed and Web of Science for English-language articles and hand-searched 7 Japanese scientific journals for Japanese-language articles. Trends in urinary sodium excretion were examined with the use of weighted linear regression and random-effects meta-regression analyses, with adjustment or stratification to address study characteristics (population mean age, percentage of men, and sample size) and study assessment for completeness of urine collection.Results: We identified 68 reports of urinary sodium excretion from 53 articles published from 1953 through 2014 that showed high rates of urinary sodium excretion in healthy Japanese adult populations (weighted mean: 4900 mg/d). The rate of urinary sodium excretion significantly decreased between 1953 and 2014, by 4350 mg/d (P < 0.001); however, the rate of reduction in urinary sodium excretion was variable and decreased with time (P-linear trend <0.001 and P-quadratic trend <0.001). In the random-effects meta-regression analysis of studies that assessed completeness of urine collection with creatinine excretion, no significant relation between urinary sodium excretion and year was observed from 1978 to 2014 (β = -16, P = 0.40).Conclusion: Despite a decrease in urinary sodium excretion in healthy Japanese adult populations between 1953 and 2014, sodium intake still exceeds the WHO recommendation for adults. This review was registered at PROSPERO as CRD42016035452.

PS 18-22 Relationship of nocturnal BP and dipping according to 24-hour urinary sodium excretion and nocturnal heart rate

PS 18-22 Relationship of nocturnal BP and dipping according to 24-hour urinary sodium excretion and nocturnal heart rate

PS 18-23 Urinary sodium excretion and heart rate as a novel marker of salt-sensitive blood pressure elevation in young male normotensive Tanzanian

PS 18-23 Urinary sodium excretion and heart rate as a novel marker of salt-sensitive blood pressure elevation in young male normotensive Tanzanian

Maintenance Intravenous Fluids in Acutely Ill Patients.

To the Editor: The recommendation by Moritz and Ayus (Oct. 1 issue)1 of 0.9% normal saline as default maintenance fluid in acutely ill patients fails to consider the increased risk of hypernatremia and volume expansion that may occur. Both complications may be potentially as damaging as the hyponatremia that the authors seek to avoid.2,3 Hypernatremia accompanies ongoing hypotonic losses, including from sweat and the urea-induced diuresis associated with nutritional supplementation, and the hypertonic gain of 0.9% saline with added potassium. By definition, maintenance represents an amount and content of fluid needed to maintain a steady state. The emergence of iatrogenic hyponatremia or hypernatremia with any one-size-fits-all prescription indicates a miscalculation of maintenance fluids for a given patient. It is necessary to first define and achieve the steady state desired, to measure or estimate all input and output volumes and electrolyte content, and to recalculate at regular intervals. Urinary sodium excretion, potassium excretion, and flow rate allow for simple calculations of a positive or negative electrolyte-free water clearance and isotonic loss. The best guideline to prevent severe complications would be an algorithm for constructing a therapeutic plan for an individual patient.

Temporally Relationship between Renal Local Clock System and Circadian Rhythm of the Water Electrolyte Excretion

To investigate the relationship of the circadian rhythm of the urine volume and urine electrolytes excretion rate and the daily expression pattern of the clock genes and clock-controlled genes with the water electrolyte transportation circadian pattern in rat kidneys. Male adult SD rats were exposed to in a light:dark (12:12) cycles. We collected two period urine from zeitgeber time (ZT)00:00-ZT12:00 (light time,rest period) and ZT12:00-24:00 (dark time,activity period) and then compared the urinary excretion rates of volume, sodium, potassium, and chloride at light time with those at dark time. Rats were sacrificed every 4 hours throughout a 24-hour day-night cycle. Circadian clock gene CLOCK, BMAL1,Per1,Per2,Cry1,Cry2 and kidney specific clock-controlled gene NHE3,αENaC、NCC,Ptges,V1aR,V2R expression were profiled by real-time quantitative polymerase chain reaction. Data were analysed by a partial Fourier analysis and a stepwise regression technique. Urine volume and urine potassium excretion rate displayed high level at dark time and low at light time in SD rats (P<0.05),and urine sodium and chloride excretion rate also showed the trend(P>0.05).Clock gene CLOCK,BMAL1,Per1,Per2,Cry1,Cry2(P<0.05)and kidney specific clock-controlled gene NHE3, αENaC, NCC, Ptges, V1aR, V2R (P<0.05)mRNA expression showed circadian pattern,and the peak times of the genes were in the dark time. Urine volume and urine electrolyte excretion rate which displayed circadian pattern were temporally coupled with the rhythm of expression of clock and clock-controlled genes associated with water electrolyte transportation in rats kidney.

Daytime cold exposure and salt intake based on nocturnal urinary sodium excretion: A cross-sectional analysis of the HEIJO-KYO study

Increased cardiovascular incidence in winter is partly explained by higher blood pressure due to cold exposure. Although higher salt intake induced by cold exposure has been reported in mice, the association remains unclear in humans. To investigate the association between salt intake and cold exposure in winter, a cross-sectional study was conducted among 860 elderly subjects (mean±standard deviation: 72.0±7.1years).We determined ambient temperature at every 10min according to indoor temperature measured in the subjects' home, outdoor temperature, and self-administered diary logging time spent outdoors. Salt intake was estimated by nocturnal sodium excretion rate of overnight urine collection. A 1°C lower daytime ambient temperature was significantly associated with a higher urinary sodium excretion rate by 0.07mmol/h in the subsequent night independent of age, sex, body weight, alcohol intake, calcium channel blocker use, diabetes, household income, estimated glomerular filtration rate, daytime physical activity (p=0.02). After further adjustment for outdoor temperature and day length, the lowest tertile groups of ambient daytime temperature (10.1±2.3°C) showed the nocturnal urinary sodium excretion rate was higher by 14.2% (7.62 vs. 6.54mmol/h) compared with the highest tertile group (19.3±1.8°C). Higher sodium excretion rate was associated with higher nighttime ambulatory blood pressure (p<0.01) and its lower nocturnal dipping (p<0.01). Significant association between higher salt intake and daytime cold exposure partly explain the mechanism of higher blood pressure in winter, and suggest that a reduction of cold exposure might be effective to decrease salt intake.

6A.09

Objective: The severity of sodium sensitivity is quantified or 1) by the difference in mean arterial pressure (MAP) between high- and low-sodium diets (δMAP), or 2) by the sodium-sensitivity index (SSI), i.e. ratio between δMAP and the difference in urinary sodium excretion rates at the end of the two diets. MAP is usually measured with an arm cuff but the use of finger blood pressure monitors is rapidly increasing. Thus, our aim is to evaluate whether finger measures of MAP can be reliably used for assessing sodium sensitivity. Design and method: We enrolled 68 normotensive volunteers who underwent high- and low-sodium diets of 5 days duration. SSI and δMAP were derived from MAP measures taken both at the arm (gold standard) and at the finger (Portapres model-2). First, volunteers were classified as sodium sensitive (SS) or resistant (SR) if δMAP measured at the arm was or not greater than 3 mmHg, and the receiver operator characteristic (ROC) analysis was performed for the SS/SR classification based on finger δMAP. Then volunteers were classified as SS or SR if SSI from arm MAP was or not greater than 20 mmHg/(mol/day), and ROC analysis was performed for the SS/SR classification based on finger SSI. Results: Fourteen individuals were classified as SS on the basis of arm δMAP greater than 3 mmHg. Similarly, 14 individuals were also classified as SS on the basis of arm SSI greater than 20 mmHg/(mol/day). Classifications based on finger measures were substantially different. In particular, finger measures of δMAP performed poorly for the SS/SR classification: the area under the ROC curve (AUC) was 0.65 only; the best threshold for classification was finger δMAP = 2 mmHg, corresponding to sensitivity = 57%, specificity = 67%. Slightly better performances were obtained for finger SSI (see figure), with AUC = 0.71. The best threshold for classification was finger SSI = 23 mmHg/(mol/day), corresponding to sensitivity = 61%, specificity = 72%.Conclusions: The assessment of sodium sensitivity depends strongly on the MAP measurement site, with important discrepancies between brachial and finger measures.