Sodium Excretion Rate Research Articles

Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites.

Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites. We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30ng/kg/min, though later reduced to 20 for safety reasons. In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. -6.2mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2-35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness. Ularitide in doses of 20-30ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.

Diuretic and Anti-Hypertensive Activity of Clerodendrum Chinense (OSBECK) MABB. Aqueous Extract in 8% Salt Diet-Induced Hypertensive Rats

Diuresis refers to an increase in the rate of urine flow and sodium excretion from the system via the urine. It is a necessary excretory process that may prove difficult for some disease systems e.g. enlarged prostates. Hypertension occurs as a result of systolic blood pressure higher than 140 mmHg or a diastolic blood pressure higher than 90 mmHg. It is one of the most common chronic diseases affecting more than a billion people worldwide. A high dietary sodium intake is one of the factors associated with the development of hypertension. Clerodendrum chinensis is used by local communities in West Africa for its diuretic and anti-hypertensive properties. We analyze the phytochemical properties of the mixed leaf, root, and stem aqueous extract of the plant and investigate its anti-hypertensive and diuretic activity in Sodium chloride diet-induced hypertensive rats. The anti-hypertensive effect of extract at different concentrations (100, 200, and 300 mg/kg) was studied and compared with a known drug compound; Furosemide. Treated animal urine was analyzed for urinary excretion and diuretic action. The anti-hypertensive effect was statistically significant when compared with the control p < 0.001. The extract at 100mg/kg demonstrated the best systolic and diastolic blood pressure lowering potential as compared to other concentrations. The diuretic action of the plant extract at the lowest dose (100 mg/kg) was high and quantitatively similar to the standard drug. The combined powdered leaf, stem and roots aqueous extract of C. chinense possesses anti-hypertensive and diuretic potential in salt-loaded hypertensive rats.

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 META

Objective: 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). Design and method: We conducted a cross-sectional, worldwide 30-item survey through e-mails. Results: 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 5 min 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. Conclusions: 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.

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 Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs.

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2-5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS.

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.

Glucocorticoids ameliorate cardiorenal syndrome through the NPR1/SGK1 pathway in natriuretic peptide receptor A‑heterozygous mice.

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome.

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.

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.

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation.

Normothermic machine perfusion (NMP) of kidneys in combination with an optimized perfusate composition may increase donor organ preservation quality, especially in the case of marginal donor grafts. Optimization of currently employed perfusates is still a subject of present research. Due to the advantages of being cell-free, easy to store, and having minimal antigenicity, hemoglobin-based oxygen carriers, such as HBOC-301 (Oxyglobin®, Hemoglobin Oxygen Therapeutics LLC, Souderton, PA, USA), offer an alternative to the commonly used perfusates based on packed red blood cells (pRBC). As previously described, using HBOC results in formation of methemoglobin (metHb) as an adverse effect, inducing hypoxic conditions during the perfusion. As a potential counterpart to metHb formation, the application of the antioxidant ascorbic acid (VitC) is of high interest. Therefore, this study was conducted in four experimental groups, to compare the effect of NMP with (1) HBOC or (3) pRBC, and additionally examine a beneficial effect of VitC in both groups (2) HBOC + VitC and (4) pRBC + VitC. All groups were subjected to NMP for 6 h at a pressure of 75 mmHg. Kidneys in the HBOC groups had a significantly lower renal blood flow and increasing intrarenal resistance, with reduced renal function in comparison to the pRBC groups, as demonstrated by significantly lower creatinine clearance and higher fractional sodium excretion rates. Clinical chemistry markers for tissue damage (LDH, lactate) were higher in the HBOC groups, whereas no significant histological differences were observed. Although the application of VitC decreased oxidative stress levels, it was not able to significantly increase the outcome parameters mentioned above in either group. This study demonstrated that HBOC-301 is inferior to pRBCs in our porcine kidney NMP model, independent of additional VitC administration. Oxidative stress and fragmentation of the hemoglobin polymers could be detected as a possible reason for these results, hence further research, focusing on the use of cell-free oxygen carriers that do not exhibit this complex of issues, is required.

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.

Kynurenine Infusion Disrupts Normal Blood Pressure Circadian Rhythms

Kynurenine is the first stable product of tryptophan metabolism, and its level increases with age. Elevated kynurenine/tryptophan ratios have been implicated in many aging‐related diseases including chronic kidney disease (CKD). We hypothesized that chronic infusion of kynurenine would induce alterations in renal‐related parameters, such as blood pressure, sodium excretion and glomerular filtration rate (GFR), that could contribute to development of age‐related CKD. In an IACUC‐approved study, three‐month‐old male Sprague Dawley rats were instrumented with aortic and venous catheters, as well as telemeters for blood pressure monitoring, and then housed in metabolic cages for urine collection. Following a five‐day control period, rats received continuous kynurenine infusion (5 mg/kg, 10 mg/kg, 50 mg/kg) or vehicle for 4 weeks. We found that GFR decreased after 2 weeks of KYN treatment [1.29 (n=5) vs. 1.51 (control, n=16) or 1.50 (vehicle, n=3) mL/min p=0.04]. The normal circadian rhythm for blood pressure was disrupted by all doses of kynurenine while heart rate maintained its normal diurnal pattern. Mean arterial pressure in kynurenine‐treated rats tended to increase over time compared to vehicle‐treated. Kynurenine infusion also induced increased water consumption. These data suggest that kynurenine treatment impacts renal function and may contribute to the development of CKD. Non‐dipping blood pressure is a significant risk factor for cardiovascular disease, even in the context of normotension. Further studies will be needed to determine the mechanism of this effect.

The Influence of Salt Sensitivity Phenotype on Sodium Excretion and Diuresis: A Chrononutrition Pilot Study.

Background Chrononutrition studies on interaction of diet/nutrients on endogenous circadian clocks and meal timing on metabolic homeostasis may be of importance in the management of nocturnal polyuria (NP), owing to loss of circadian rhythm in nighttime urination. Dietary salt restriction is an increasingly popular lifestyle recommendation for NP patients. Aim This study aims to evaluate the effect of an acute salt load on diuresis and to study the phenomenon of salt sensitivity. Methodology. Young, healthy men (n = 21, fasted and sober) ingested 500 ml of water on the control day and 8 g and 12 g of salt with water (500 ml) on two other days. Blood and urine samples were collected at 0 hrs, 2 hrs, and 4 hrs and voided volumes were recorded. Diuresis, serum and urine osmolality, sodium, potassium, urea, and creatinine were measured. Salt sensitivity was determined based on the rate of sodium excretion. Results Compared to 8 g, ingestion of 12 g of salt significantly increased diuresis after 4 hrs. Pure water load induced fast diuresis, whereas salt and water load initially reduced diuresis and promoted late increase in diuresis. The total voided volume was significantly lower in the salt sensitive individuals. Conclusion Taken together, salt sensitivity profile and type and time of fluid intake are important considerations to build effective personalized lifestyle recommendations for NP patients, which needs further investigation.

Estimating urine volume from the urine creatinine concentration.

Spot determinations of the urine creatinine concentration are widely used as a substitute for 24-h urine collections. Expressed as the amount excreted per gram of creatinine, urine concentrations in a single-voided sample are often used to estimate 24-h excretion rates of protein, sodium, potassium, calcium, magnesium, urea and uric acid. These estimates are predicated on the assumption that daily creatinine excretion equals 1 g (and that a urine creatinine concentration of 100mg/dL reflects a 1 L 24-h urine volume). Such estimates are invalid if the serum creatinine concentration is rising or falling. In addition, because creatinine excretion is determined by muscle mass, the assumption that 24-h urine creatinine excretion equals 1 g yields a misleading estimate at the extremes of age and body size. In this review, we evaluate seven equations for the accuracy of their estimates of urine volume based on urine creatinine concentrations in actual and idealized patients. None of the equations works well in patients who are morbidly obese or in patients with markedly decreased muscle mass. In other patients, estimates based on a reformulation of the Cockroft-Gault equation are reasonably accurate. A recent study based on this relationship found a high strength of correlation between estimated and measured urine output with chronic kidney disease (CKD) studied in the African American Study of Kidney Disease (AASK) trial and for the patients studied in the CKD Optimal Management with Binders and NictomidE (COMBINE) trial. However, the equation systematically underestimated urine output in the AASK trial. Hence, an intercept was added to account for the bias in the estimated output. A more rigorous equation derived from an ambulatory Swiss population, which includes body mass index and models the non-linear accelerated decline in creatinine excretion with age, could potentially be more accurate in overweight and elderly patients. In addition to extremes of body weight and muscle mass, decreased dietary intake or reduced hepatic synthesis of creatine, a precursor of creatinine or ingestion of creatine supplements will also result in inaccurate estimates. These limitations must be appreciated to rationally use predictive equations to estimate urine volume. If the baseline urine creatinine concentration is determined in a sample of known volume, subsequent urine creatinine concentrations will reveal actual urine output as well as the change in urine output. Given the constraints of the various estimating equations, a single baseline timed collection may be a more useful strategy for monitoring urine volume than entering anthropomorphic data into a calculator.

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.

Impaired Daytime Urinary Sodium Excretion Impacts Nighttime Blood Pressure and Nocturnal Dipping at Older Ages in the General Population.

The circadian rhythm of urinary sodium excretion is related to the diurnal blood pressure regulation (BP) and the nocturnal dipping pattern. The renal sodium excretion expressed as daytime/nighttime ratio impacts BP, but a limited number of studies have investigated this topic to date. In this cross-sectional study, we aimed to investigate the impact of different daily patterns of sodium excretion (comparing low with high ratios) on BP and nocturnal dipping and to explore the relationship with age. Twenty-four-hour ambulatory BP monitoring and daytime and nighttime urinary sodium collections were used to assess 1062 subjects in Switzerland. Analyses were performed according to the day/night urinary sodium excretion ratio quartiles (Q1–Q4) and by age group (≤50 and ≥50 years). Subjects in Q1 can be considered low excretors of sodium during the daytime since the rate of sodium excretion during the daytime was 40% lower than that of subjects in Q4. Quartiles of the day/night urinary sodium excretion ratio showed that subjects in Q1 were 7 years older and had respectively 6 and 5 mmHg higher nighttime systolic and diastolic BP and a higher nocturnal dipping compared with subjects in Q4 (p-value ≤0.001). Associations found were significant only for subjects older than 50 years (all p < 0.05). The present results suggest that a decreased capacity to excrete sodium during daytime is more prevalent as age increases and that it impacts nighttime blood pressure and nocturnal dipping in older subjects.