Low Urinary Sodium Research Articles

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Spot urinary sodium as a prognostic marker for mortality in patients with acute decompensated heart failure

Introduction. Urinary sodium has been proposed as a prognostic marker and indicator of the diuretic response in patients with heart failure. However, study results are heterogeneous. Objective. To evaluate the spot urinary sodium level as a risk factor for mortality in patients with decompensated heart failure. Materials and methods. We conducted a case-control study nested in a prospective cohort of patients with decompensated heart failure. The primary outcome was mortality at 180 days. The risk factors associated with mortality were evaluated through a bivariate analysis. Differences in clinical variables between groups with urinary sodium greater than or lesser than 70 mEq/L were analyzed. Results. The study included 79 patients; 15 died at 180 days. Their mean age was 68.9 years (SD=± 13.8); 30 were women (38%), and 15 (18.9%) had urinary sodium <70 mEq/L. In the bivariate analysis, a significant association was found between mortality and past medical history of hospitalizations, SBP<90 mm Hg, the use of inotropes, and urinary sodium <70 mEq/L. Regarding clinical characteristics, patients with low urinary sodium level in the last year were hospitalized more frequently with hyponatremia and hypotension at admission. Conclusion. Patients with urinary sodium <70 mEq/L had more severe signs. In a bivariate analysis, urinary sodium was associated with mortality at 180 days.

Association of serum sodium and 24-hour urinary sodium level with the severity and complications of ascites in cirrhotic patients.

Hyponatremia is an independent predictor of mortality in cirrhotic patients but little is known regarding the relationship between the level of serum sodium and 24-hour urinary sodium with the development of severity and complications of cirrhotic ascites. To observe the association of serum sodium and 24-hour urinary sodium levels with different grades of ascites and its complications in cirrhotic patients. In the department of Gastroenterology in a tertiary care hospital, this cross-sectional study was conducted from April 2019 to September 2020. A total of 96 admitted cirrhotic patients with ascites were enrolled in this study by consecutive sampling. Out of 96 patients with cirrhotic ascites, 48 patients had mild, moderate, and severe ascites and 48 patients had complications of ascites like refractory ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome. The mean serum sodium level was 131.69 ± 4.90 and 124.88 ± 5.67 mmol/L and the 24-hour urinary sodium level was 76.82 ± 45.64 and 35.26 ± 22.57 mmol/L in uncomplicated and complicated ascites groups respectively with P value < .001. In grade 1, grade 2, and grade 3 ascites, there was a significant (P = .001), association between mean serum sodium (mmol/L) level (R -0.777) and 24-hour urine sodium (mmol/L) level (R -0.704) but no significant difference was seen when refractory ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome were considered. In our finding, low serum sodium and low 24-hour urinary sodium levels were associated with the development of severe complications of cirrhotic ascites. Hence, Serum sodium and 24-hour urinary sodium levels can be good predictors of grading and complications of cirrhotic ascites.

Sodium depletion and secondary hyperaldosteronism in outpatients with an ileostomy: a cross-sectional study

Objective Patients with an ileostomy may experience postoperative electrolyte derangement and dehydration but are presumed to stabilise thereafter. We aimed to investigate the prevalence of sodium depletion in stable outpatients with an ileostomy and applied established methods to estimate their fluid status. Methods We invited 178 patients with an ileostomy through a region-wide Quality-of-Life-survey to undergo outpatient evaluation of their sodium and fluid status. The patients delivered urine and blood samples, had bioelectrical impedance analysis performed and answered a questionnaire regarding dietary habits. Results Out of 178 invitees, 49 patients with an ileostomy were included; 22 patients (45%, 95% CI, 31–59%) had unmeasurably low urinary sodium excretion (<20 mmol/L), indicative of chronic sodium depletion, and 26% (95% CI, 16–41%) had plasma aldosterone levels above the reference value. Patients with unmeasurably low urinary sodium excretion had low estimated glomerular filtration rates (median 76, IQR 63–89, mL/min/1.73m2) and low venous blood plasma CO2 (median 24, IQR 21–26, mmol/L), indicative of chronic renal impairment and metabolic acidosis. Bioelectrical impedance analysis, plasma osmolality, creatinine and sodium values were not informative in determining sodium status in this population. Conclusion A high proportion of patients with an ileostomy may be chronically sodium depleted, indicated by absent urinary sodium excretion, secondary hyperaldosteronism and chronic renal impairment, despite normal standard biochemical tests. Sodium depletion may adversely affect longstanding renal function. Future studies should investigate methods to estimate and monitor fluid status and aim to develop treatments to improve sodium depletion and dehydration in patients with an ileostomy. IMPACT AND PRACTICE RELEVANCE STATEMENT Sodium depletion in otherwise healthy persons with an ileostomy was identified in a few publications from the 1980s. The magnitude of the problem has not been demonstrated before. The present study quantifies the degree of sodium depletion and secondary hyperaldosteronism in this group, and the results may help guide clinicians to optimise treatment. Sodium depletion is easily assessed with a urine sample, and sequelae may possibly be avoided if sodium depletion is detected early and treated. This could ultimately help increase the quality of life in patients with an ileostomy.

PS-BPB10-1: INVOLVEMENT OF RENAL TUBULAR NFAT5 IN THE REGULATION OF BLOOD PRESSURE AND BODY FLUID VOLUME

Objective: Nuclear factor of activated T-cells 5 (NFAT5) is an osmoresponsive transcription factor that activates osmoprotective genes to protect cells against hypertonicity. Renal tubular cell-specific NFAT5 knockout (KO) mice have been shown to exhibit polyuria, hypernatremia, low urinary sodium excretion, and increased expression of the epithelial sodium channel (ENaC) in the kidney. In the present study, regulation of blood pressure (BP) as well as that of body fluid volume were examined in the wild type (WT) mice and NFAT5 KO mice. Methods: The BP of KO mice and WT mice was measured using radiotelemetry method. The mice were fed with regular salt diet (RSD, 0.3% NaCl chow) or high salt diet (HSD, 8% NaCl chow) followed by the treatment with amiloride, an ENaC blocker. To assess body fluid volume, the plasma renin activity (PRA) and the plasma aldosterone concentration (PAC) were measured at the condition of RSD and HSD, together with plasma arginine vasopressin (AVP) and hematocrit (Ht) levels. Results: Compared to WT mice, the mean BP was significantly higher in KO mice both at the condition with RSD and that with HSD in dark period, but not in light period. Treatment with amiloride significantly decreased the mean BP in KO mice with HSD to the level of WT mice with HSD in dark period. PRA, PAC, and AVP levels were not significantly different between in WT and KO mice with RSD. HSD significantly decreased PRA and PAC and tended to increase the AVP level both in WT and KO mice. The Ht level was significantly lower in KO mice than in WT mice regardless of RSD or HSD (WT with RSD, 42.6 ± 0.5%; WT with HSD, 42.8 ± 0.6%; KO with RSD, 38.3 ± 0.4%; KO with HSD, 39.0 ± 0.4%, n = 4). Conclusions: The results suggest that the renal tubular cell-specific NFAT5 KO mice exhibit excess body fluid retention induced by sodium reabsorption through ENaC, leading to salt-sensitive hypertension. Such phenotypes seem to be independent of the systemic renin-angiotensin-aldosterone and AVP systems. Renal tubular NFAT5 could integrate urine concentration and sodium reabsorption in the kidney, thus preventing salt-dependent hypertension.

Assessment of Intravascular Volume Status in Children with Nephrotic Edema Using Serum and Urinary Indices and Its Correlation with Inferior Vena Cava Collapsibility Index.

Identification of volume status in nephrotic syndrome (NS) is important but clinically challenging. Urinary and serum indices can be helpful in assessing the volume status and so can be inferior vena cava collapsibility index (IVCCI). This study was done to assess the serum and urinary indices in children with nephrotic edema and to correlate them with IVCCI for intravascular volume assessment. Fifty children with nephrotic edema and 47 children in remission were analyzed for blood and urine indices. Volume status was defined as overfilling or underfilling based on the biochemical indices and also by IVCCI. Eighty-four percent individuals among cases and 23% among controls had sodium retention (FENa < 0.5%). Among cases, 54% had primary sodium retention compared to 17% among controls (p = 0.0002). Hypovolemia was observed among 36% cases based on biochemical indices and in 20% cases as per IVCCI. Hypovolemia was significantly associated with low urinary sodium and low serum albumin.

Hypercalcemia Induced Nephrogenic Diabetes Insipidus with Symptomatic Hypernatremia

Nephrogenic Diabetes Insipidus (NDI) can be acquired or congenital. There is an inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron-collecting duct to the antidiuretic hormone, arginine vasopressin. The diagnosis is made with a water deprivation test and patients will have inappropriately low urine osmolarity and sodium despite water deprivation. Causes of acquired nephrogenic diabetes insipidus include chronic lithium ingestion, hypercalcemia and hypokalemia.

Urinary Sodium Excretion Enhances the Effect of Alcohol on Blood Pressure.

Alcohol consumption is linked to urinary sodium excretion and both of these traits are linked to hypertension and cardiovascular diseases (CVDs). The interplay between alcohol consumption and sodium on hypertension, and cardiovascular diseases (CVDs) is not well-described. Here, we used genetically predicted alcohol consumption and explored the relationships between alcohol consumption, urinary sodium, hypertension, and CVDs. Methods: We performed a comparative analysis among 295,189 participants from the prospective cohort of the UK Biobank (baseline data collected between 2006 and 2010). We created a genetic risk score (GRS) using 105 published genetic variants in Europeans that were associated with alcohol consumption. We explored the relationships between GRS, alcohol consumption, urinary sodium, blood pressure traits, and incident CVD. We used linear and logistic regression and Cox proportional hazards (PH) models and Mendelian randomization in our analysis. Results: The median follow-up time for composite CVD and stroke were 6.1 years and 7.1 years respectively. Our analyses showed that high alcohol consumption is linked to low urinary sodium excretion. Our results showed that high alcohol GRS was associated with high blood pressure and higher risk of stroke and supported an interaction effect between alcohol GRS and urinary sodium on stage 2 hypertension (Pinteraction = 0.03) and CVD (Pinteraction = 0.03), i.e., in the presence of high urinary sodium excretion, the effect of alcohol GRS on blood pressure may be enhanced. Conclusions: Our results show that urinary sodium excretion may offset the risk posed by genetic risk of alcohol consumption.

Low-Flow Acute Kidney Injury: The Pathophysiology of Prerenal Azotemia, Abdominal Compartment Syndrome, and Obstructive Uropathy.

AKI is a syndrome, not a disease. It results from many different primary and/or secondary etiologies and is often multifactorial, especially in the hospitalized patient. This review discusses the pathophysiology of three etiologies that cause AKI, those being kidney hypoperfusion, abdominal compartment syndrome, and urinary tract obstruction. The pathophysiology of these three causes of AKI differs but is overlapping. They all lead to a low urine flow rate and low urine sodium initially. In all three cases, with early recognition and correction of the underlying process, the resulting functional AKI can be rapidly reversed. However, with continued duration and/or increased severity, cell injury occurs within the kidney, resulting in structural AKI and a longer and more severe disease state with increased morbidity and mortality. This is why early recognition and reversal are critical.

Clinic and ambulatory blood pressure in relation to the interaction between plasma advanced glycation end products and sodium dietary intake and renal handling.

Advanced glycation end product (AGE) clearance may cause renal tubular injuries, such as changes in sodium reabsorption. We hypothesize that AGEs interact with sodium metabolism to influence blood pressure (BP). The study participants were outpatients who were suspected of having hypertension but had not been treated with antihypertensive medication. Clinic and ambulatory blood pressures were measured at baseline (n = 989) and during follow-up (median, 4.4 years, n = 293). Plasma AGE concentrations were measured by enzyme-linked immunosorbent assay. Twenty-four-hour urine was collected for measurements of creatinine, sodium and lithium. In a cross-sectional analysis (n = 989), subjects in the top quintile versus quintiles 1-4 of plasma AGE concentration had significantly (P ≤ 0.004) lower fractional excretion of lithium (18.3% vs. 21.6%) and fractional distal reabsorption rate of sodium (95.0% vs. 95.8%) but similar BP (P ≥ 0.25). However, there was an interaction between plasma AGE concentration and urinary sodium excretion in relation to diastolic BP (P ≤ 0.058). Only in participants with low urinary sodium chloride excretion (≤6 grams/day, n = 189), clinic (84.3 vs. 80.2 mmHg), 24-h (83.9 vs. 80.4 mmHg), daytime (87.8 vs. 84.8 mmHg) and nighttime (75.1 vs. 72.1 mmHg) diastolic BP at baseline were higher (P ≤ 0.05) in the top quintile than in quintiles 1-4 of plasma AGE concentration. In the longitudinal study (n = 383), similar trends were observed, with significant (P ≤ 0.05) differences in the increment in daytime diastolic BP (6.8 vs. -1.7 mmHg) and incidence of ambulatory and treated hypertension (hazard ratio 3.73) during follow-up. In conclusion, AGEs were associated with high BP, probably via enhanced proximal sodium handling and on low dietary sodium intake.

Salt-Sensitive Hypertension of the Renal Tubular Cell-Specific NFAT5 (Nuclear Factor of Activated T-Cells 5) Knockout Mice.

[Figure: see text].

Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure.

In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown. Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13-17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47). On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.

MO172HYPONATREMIA IN PATIENTS WITH COVID19

BackgroundAmong laboratory abnormalities described in the context of SARS-COV-2 infection, hyponatremia seem to be the most common. The mechanism of this sodium disbalance is not well known.AimsCharacterize the incidence, etiology and prognostic value of sodium disbalance in patients with COVID19.MethodObservational pilot study with 37 patients admitted to Hospital Ramon y Cajal in Madrid, Spain, between March and April 2020, with a confirmed diagnosis of COVID19. Patients were followed until discharge or death. Clinical and laboratory data were collected at admission and before the clinical outcome. Variables were analyzed comparing hyponatremic vs eunatremic patients.ResultsDistribution of patients according to their serum sodium was as follows: 16 patients with hyponatremia (44%), 19 with normal serum sodium (51%) and 2 with hypernatremia (5%). The average sodium level in hyponatremic patients was 130 ±3.2 mmol/l, median urine sodium was 36 ±3.2 mmol/l (only 6 urine sample available). Hyponatremia was associated with dyspnea at admission and with higher levels of LDH, neutrophil cells account and C reactive protein. However, no worse prognostic was associated with lower serum sodium. All patients recover sodium levels at discharge treated with salt supplementation and free water intake.Conclusionmild hyponatremia is a common electrolyte disorder associated with COVID19. Sing as low urine sodium and recover with water and salt ingestion, point toward hydrosaline dehydration instead of SIADH as most common origin of hyponatremia.

Interesting and Rare Case of Central Diabetes Insipidus in a Patient With Acute Myeloid Leukemia

Introduction: Central Diabetes Insipidus (CDI) is the lack of antidiuretic hormone (ADH) leading to impaired urinary concentration and manifests with extreme thirst and excessive urination. Patients unable to drink fluids are at risk of severe dehydration and hypernatremia. CDI can be a rare complication of acute myeloid leukemia (AML). The occurrence of AML with CDI is extremely rare with only few case reports published. This combination of AML with CDI has been reported to be associated with monosomy 7 and inversion (3) (q21q26) and portends an overall a very poor treatment response resulting in poor outcomes.Case Presentation: 66-year-old female with hypertension, polycythemia vera diagnosed in 2006 with transformation to AML in 2020. FISH studies revealed monosomy 7. Cytogenetic studies showed inv (3)(q21q26.2). Remission induction chemotherapy was initiated. Subsequently, neutropenic fever and sepsis secondary to Clostridium difficile colitis lead to hospitalization. Her sodium (Na) level gradually trended up and reached a peak of 157 mmol/l (range 136-145) and elevated serum osmolality at 311 mOsm/K with low urine osmolality 135 mOsm/K, low urine sodium at 13 and low urine specific gravity 1.006 concerning for CDI. She developed polyuria and received desmopressin (DDAVP) leading to improvements in urine osmolality to 267 mOsm/K, 30 minutes indicating CDI diagnosis. Her Na gradually normalized to 144 mmol/l, urine osmolality improved to 580 mOsm/K and urine specific gravity to 1.025. She is now on DDAVP 0.05 mg oral twice daily and her Na is in normal range. MRI pituitary did not show any evidence of metastatic lesion with intact pituitary bright spot. Her other pituitary hormonal workup was normal except for hypogonadotropic hypogonadism.Discussion: The pathophysiology of AML and CDI is unclear. Leukemic cells infiltration of the neurohypophysis; thrombosis of small vessels in hypothalamic nuclei and the posterior pituitary; alterations of the neutrophil migration placed on the chromosome 7 leading to glycoprotein gp 130 production, a cell surface marker on granulocytes are some of hypothesis suggested. CDI has a variable onset in the course of myeloid malignancies. MRI pituitary can be normal in most of the cases.

Severe Symptomatic SIADH as a Sign of Unknow Hypopituitarism: A Case Report

Abstract Background: SIADH due to secondary adrenal insufficiency is a rare condition that can be life-threatening. Treatment with glucocorticoids is highly effective, but, as symptomatology of hypopituitarism can be mild and unspecific, a high level of clinical suspicion is necessary. Clinical Case: A 64-year-old postmenopausal woman, with a previously diagnosed and treated hypothyroidism and depressive syndrome, presented at the emergency room with nausea, vomits, asthenia and recurrent syncopes over the past three weeks and weight loss in the last months. One week before, she had been admitted at other hospital due to the same complaints and a serum Na+ of 112mmol/L (N 135-145 mmol/L) was detected. One year earlier, she had reported the same symptomology and hyponatremia had also been found, but no etiologic study was performed. At admission, she was conscient, hydrated, pale, hemodynamically stable, with unremarkable cardiopulmonary auscultation. A severe hyponatremia was found (Na+ 111mmol/L), with low serum osmolarity (241mOsm/Kg, N 280-301mOsm/Kg), low urine osmolality (125mOsm/kg N 300-900 mOsm/Kg) and low urinary sodium (33mmol/24h, N 40-220mmol/24h). Treatment with saline fluids was initiated and the patient was admitted for etiological investigation, which showed a low morning serum cortisol (3.7 µg/dl)) with inappropriately low-normal ACTH level (12.2 pg/mL), low FSH (15.07 mUI/mL, N 23.0-116.3 mUI/mL) and LH (4.28 mUI/mL, N 15.9-54 mUI/mL), estradiol of 78.81 pmol/L (N &amp;lt;118.2 pmol/L), undetectable IGF-1 (&amp;lt;25 ng/mL, N 36-244 ng/mL) and PRL of 21.98 ng/mL (N 1.8-20.3 ng/mL). Under 50µg of levothyroxine, TSH was 2.5 µUI/mL (N 0.358-3.74 µUI/ml), and FT4 was 1.1 ng/dL (N 0.76-1.46 ng/dL). Anti-thyroglobulin and anti-TPO antibodies were negative. A pituitary MRI revealed an empty sella with arachnoidocele. Other differential diagnosis of SIADH were excluded. The patient was started on oral hydrocortisone 30 mg/day, with a remarkable recovery, with better mood, more energy and appetite, resolution of all symptoms and normalization of the natremia. Conclusion: Hypopituitarism due to an empty sella is a relative rare disorder, whose etiology may be difficult to prove. It usually develops insidiously, with unspecific symptoms, which often delays the diagnosis. In our patient, this severe hyponatremia likely developed over a long time, allowing adaptation to such low levels of Na+. Moreover, the presence of a previously diagnosed hypothyroidism raises the suspicion if this wasn’t the first manifestation of the pituitary disease and if treatment of levothyroxine did not worsen an undetected secondary adrenal insufficiency.

EFFECTS OF DAPAGLIFLOZIN IN HIGH AND LOW DIETARY SALT INTAKE PATIENTS WITH ALBUMINURIC DIABETIC KIDNEY DISEASE: A SUBANALYSIS OF THE Y-AIDA STUDY

Objective: Current guidelines recommend the intensive control of BP as well as blood glucose to reduce albuminuria and prevent the development of diabetic kidney disease (DKD). We reported that improved home BP profile with dapagliflozin is independently associated with amelioration of albuminuria in Japanese patients with DKD (Kinguchi, et al. Cardiovasc Diabetol. 2019). The aim of this subanalysis was to investigate the differences in home BP lowering effects between high and low dietary salt intake patients with albuminuric DKD. Design and method: The Yokohama Add-on Inhibitory efficacy of Dapagliflozin on Albuminuria in Japanese patients with type 2 diabetes (Y-AIDA) study was a prospective, multicenter, single-arm study. A total of 86 T2DM (HbA1c 7.0–10.0%) individuals with albuminuric DKD (UACR &gt; = 30 mg/gCr, eGFR &gt; = 45 ml/min/1.73m2) were enrolled, and 85 participants were administered with add-on dapagliflozin for 24 weeks. Subgroup analysis, in which patients were classified into 2 groups according to their urinary sodium excretion at baseline, was conducted to determine the change from baseline in home BP profile at week 24. Results: At baseline, office systolic BP and morning, evening, and nocturnal home systolic BP were comparable between high urinary sodium excretion group (high group) and low urinary sodium excretion group (low group) (144.0 ± 19.7 vs 140.4 ± 18.4, P = 0.4044; 138.5 ± 12.1 vs 136.4 ± 16.6, P = 0.5179; 137.4 ± 17.6 vs 134.4 ± 17.3, P = 0.4481; 124.7 ± 14.8 vs 125.9 ± 14.9, P = 0.7267). The change in evening home systolic BP was greater in high group than in low group (-13.1 ± 12.0 vs -6.4 ± 11.4, P = 0.0203). The change in office BP, and morning and nocturnal home BP were comparable between high group and low group. Conclusions: In albuminuric DKD patients who have high dietary salt intake, add-on dapagliflozin treatment resulted in a greater decrease in evening home BP than in those who have low dietary salt intake.

Twenty six-week repeat dose oral rat toxicity study of cizolirtine, a substance-P and calcitonin gene-related peptide release modulator

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.

Aldosterone sensitivity: an opportunity to explore the pathogenesis of hypertension.

Aldosterone sensitivity is defined as an outcome variable for a given circulating level of aldosterone. In basic and translational studies, aldosterone sensitivity has been measured in differential tissue responses, e.g., lower urine sodium and higher urine potassium, as an index of the renal response; in clinical studies, aldosterone sensitivity has been measured in differential blood pressure responses. The concept of aldosterone sensitivity disrupts the conventional wisdom of the renin-angiotensin-aldosterone system and has the potential to uncover novel mechanisms of hypertension. Here, we review basic and translational science studies that uncovered differential renal responses to aldosterone and connect this earlier work to more recent observational studies and randomized trials that have demonstrated differential blood pressure responses for a given level of aldosterone in healthy and hypertensive persons. Black race and older age are associated with higher aldosterone sensitivity and blood pressure. We also discuss gaps in the field and how future basic and clinical studies might inform mechanisms of differential sensitivity.

Evaluation of urinary chloride dipsticks for the rapid estimation of hydration status in patients receiving artificial nutrition: Feasibility study

The home parenteral nutrition (HPN) population face many challenges, especially with respect to fluid balance management. A low urinary sodium concentration of <20mmol/L is commonly used as an indicator of dehydration that requires clinical assessment in these patients. The Quantab titrator dipstick measures chloride concentration of a solution and correlates with sodium concentration. We assessed whether it would be feasible to use the Quantab dipstick in the HPN population and explored relationships between Quantab dipstick estimated chloride concentration and quality of life (QOL). Patients on HPN were asked to collect urine samples at 5 specific times points (day 0,7,14, 21 and 28) to send to the laboratory for formal electrolyte analysis. The participant and a member of laboratory staff tested these samples with the Quantab dipstick to estimate urinary chloride concentration. Participants were instructed to complete a QOL questionnaire at each of the 5 time-points in addition to a baseline demographic questionnaire and an end-of-study questionnaire. Six participants completed an interview at the end of the study period. The relationship between participant-derived and laboratory-derived data was assessed using rank correlation coefficients. QOL assessment was correlated with urine dipstick measurements. 10 patients on HPN completed the study. Data on chloride concentration as estimated by the dipstick (assessed by participants and by the laboratory) and sodium concentration from the laboratory were available for 47 urine samples. There was a positive relationship between participant dipstick estimated chloride concentration and laboratory sodium (Kendall's τ=0.45; P<0.001; Spearman's rs=0.58P<0.001; 47 pairs). There was a strong correlation between chloride concentrations estimated by dipstick in the laboratory and by participants (Kendall 0.58 p<0.001, Spearman's 0.69 p<0.001; 47 pairs). In exploratory analyses, there was no relationship between QOL and dipstick estimated chloride concentration. Participants had no issues collecting urine samples but some difficulties were reported with determining the dipstick reading. Patients on HPN are able to collect urine specimens, complete QOL questionnaires, and are capable of using the Quantab dipstick to estimate urinary chloride concentration. The Quantab dipstick correlates with laboratory measured sodium and chloride concentrations. Further work is required to fully establish whether this point-of-care test could be used to guide fluid balance management in the HPN population.

Abstract 12895: Tissue Sodium Content Increases With Severity of Chronic Heart Failure

Introduction: Heart failure is strongly linked to renal sodium and water retention as well as intravascular and interstitial fluid shifts. Experimental studies demonstrated a non-osmotic sodium storage, bound to proteoglycans, in the extravascular space. New sodium magnetic resonance imaging ( 23 Na-MRI) enables us to quantify tissue (muscle and skin) sodium content in a reliable and accurate way. Hypothesis: We hypothesised that the increase of tissue sodium content is dependent on the severity of chronic heart failure (CHF). Methods: We investigated patients with stable CHF before initiating treatment with an SGLT2-inhibitor within a prospective, placebo-controlled study. We here report the baseline data of 64 patients with CHF, defined as patients with reduced (HFrEF) or mid-range ejection fraction (HFmEF). In each patient, tissue sodium content of the lower leg was assessed non-invasively by a clinical 3.0T 23 Na-MRI. The median NT-proBNP plasma level at baseline was 493.3pg/ml (IQR: 225.8-1122.0pg/ml) and was used as cut off value of CHF severity. Results: Our patients (men: n=54) were 66.9±8.9 years old and had NYHA class II-III; mean muscle sodium content was 19.1±3.8mmol/l and mean skin sodium content was 22.5±5.9mmol/l. Our reference for young healthy subjects are 18.7±2.0 mmol/l for muscle sodium content and 19.6±3.1 mmol/l for skin sodium content. Patients with CHF and NT-proBNP levels above the median showed higher muscle (20.2±3.5 vs 17.9±3.7mmol/l, p=0.008) and skin sodium content (24.1±6.8 vs 20.8±4.4mmol/l, p=0.005) than patients with CHF and NT-proBNP levels below the median. No difference in plasma sodium levels between the two groups (138.0±3.7 vs 138.8±2.1mmol/l, p=0.527) was observed, but patients with NT-proBNP levels above the median had lower urinary sodium excretion over 24 hours (167.0±78.8 vs 172.3±63.4mmol/l, p=0.009). Age was different in the two groups (69.88±8.2 vs 63.8±8.7, p&lt;0.001) with no difference in gender. The number of diagnosed coronary heart disease was similar in the two groups (62.5% vs 59.4%, p=0.802). Conclusion: Concluding, tissue sodium content in patients with stable CHF as assessed by 23 Na-MRI increases with the severity of CHF. A decrease of tissue sodium content might be a future therapeutic goal.