Low Urinary Sodium Research Articles

Association of Low Urinary Sodium Excretion With Increased Risk of Stroke

The positive relationship between sodium intake and blood pressure is well established. However, results of observational studies on dietary sodium intake and risk of stroke are inconsistent. Moreover, prospective studies with multiple 24-hour urine samples for accurate estimation of habitual sodium intake are scarce. We examined the association of urinary sodium excretion (UNaV) as an accurate estimate of intake with risk of stroke. We studied 7330 individuals free of cardiovascular events at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women. The UNaV was measured in two 24-hour urine specimens at baseline (1997-1998) and two specimens during follow-up (2001-2003). Baseline median UNaV was 137 mmol/24 h (interquartile range, 106-171 mmol/24 h). During a median follow-up of 12.5 years (interquartile range, 11.9-12.9 years), a total of 183 stroke events occurred. An inverse association between UNaV and risk of stroke was observed after adjustment for age and sex (hazard ratio [HR] per 1-SD [51 mmol/24 h] decrement, 1.36; 95% CI, 1.11-1.65), which remained independent of additional adjustment for anthropometric, dietary, lifestyle, and other potential confounding factors (HR, 1.44; 95% CI, 1.14-1.82). After adjustment for potential mediators (systolic blood pressure and antihypertensive medication, plasma renin, aldosterone, and sodium levels), the association of UNaV with risk of stroke remained unchanged, with HRs (95% CIs) of 1.44 (1.14-1.82), 1.50 (1.18-1.90), 1.54 (1.21-1.97), and 1.49 (1.17-1.90), respectively. This prospective study revealed an association of low UNaV with an increased risk of stroke.

Nutritional Status in the First 2 Years of Life in Cystic Fibrosis Diagnosed by Newborn Screening.

To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24. A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome, and biological nutritional parameters. One hundred and five infants were recruited and 99 completed the study. Nutritional care management prevented undernutrition and stunting in those with exocrine pancreatic sufficiency (EPS), but affected (13/87) 15% and (21/86) 24%, respectively, of infants with exocrine pancreatic insufficiency (EPI). The logistic regression model found a positive association between both weight and length z scores "at risk" at month 24, and initial pulmonary symptoms (odds ratio [OR] 0.06, P < 0.01 and OR 0.08, P < 0.01, respectively); these symptoms were less frequent when age at first visit was earlier than 1.2 months (33% vs 67%, P = 0.02); stunting was also associated with high-calorie density intake and Staphylococcus aureus (OR 0.05, P = 0.01 and OR 0.17, P < 0.01). Pulmonary outcome did not differ according to pancreatic status; breast-feeding for at least 3 months delayed first acquisition of Pseudomonas aeruginosa. Despite sodium and fat-soluble vitamin supplementation, half of both cohorts had low urinary sodium output and half of the EPI cohort had low vitamin D levels. Our data shed light on the fact that stunting was more frequent than undernutrition, while both parameters involved only patients with pancreatic insufficiency. Modalities of feeding were not associated with nutritional status; breast-feeding may provide some protection against acquisition of P aeruginosa.

Preterm Adolescents Exhibit Higher Blood Pressure and Sodium Retention with Higher Uric Acid and Differential Circulating Renin‐Angiotensin System Expression

Preterm birth increases the risk of developing early cardiovascular disease in the future, but the underlying mechanisms are poorly understood. We previously showed that adolescents born preterm have higher blood pressure (BP), blunted pressure natriuresis, higher angiotensin II (Ang II) but lower Ang‐(1–7), and higher uric acid. The influence of preterm birth on uric acid metabolism may foster an increased risk of cardiovascular disease in part through chronic alterations in the renin‐angiotensin system (RAS) and increased sodium retention. Thus, we hypothesize that the preterm birth‐induced increase in uric acid correlates with higher BP, attenuated sodium excretion, and differential RAS expression with higher Ang II and lower Ang‐(1–7) in adolescence.A cohort of 175 adolescents born preterm was compared to 51 term controls. We recorded systolic and diastolic BP z‐scores. Circulating levels of Ang II and Ang‐(1–7) were quantified, their ratio calculated, and evaluated in relation to serum uric acid, spot urine sodium‐to‐creatinine ratios, and BP using Spearman correlation coefficients and generalized linear models by preterm birth status.Compared to those born term, adolescents born preterm had higher mean systolic and diastolic BP z‐scores (−0.4 vs −0.86, p&lt;0.001, and −0.26 vs −0.53, p=0.03, respectively) and a higher rate of hypertension (12% vs 2%, p=0.03). Higher SBP z‐score correlated with a higher Ang II:Ang‐(1–7) ratio (coefficient 0.18, p=0.02) and higher uric acid (β: 0.11 mg/dL, 95% CI 0.002 to 0.22 mg/dL). Higher serum uric acid correlated with lower Ang‐(1–7) (β: −0.02 pmol/L, 95% CI −0.04 to −0.001 pmol/L) and a higher Ang II:Ang‐(1–7) ratio (β: 0.04, 95% CI 0.008 to 0.08). Plasma Ang II correlated with a lower urine sodium:creatinine ratio (β: −0.01 pmol/L, 95% CI −0.02 to −0.004 pmol/L), a relationship that was stronger in adolescents born preterm compared to term (β: −0.01 pmol/L, 95% CI −0.02 to −0.001 pmol/L vs β: 0.001 pmol/L, 95% CI −0.009 to 0.01 pmol/L, interaction term p=0.04).In summary, the present study finds that in adolescents born preterm who have higher uric acid, BP, plasma Ang II, and lower Ang‐(1–7), higher plasma Ang II relative to Ang‐(1–7) correlated with higher serum uric acid, lower urinary sodium excretion, and higher BP. We propose that prematurity may increase the risk of early cardiovascular disease in part through increased circulating levels of uric acid that may differentially influence the expression of Ang II and Ang‐(1–7), leading to increased sodium retention and elevated BP.Support or Funding InformationEunice Kennedy Shriver National Institute of Child Health and Human Development (P01 HD047584; HD084227), the American Heart Association (AHA 14GRNT20480131), the Clinical Research Unit of Wake Forest Baptist Medical Center (MCRR/NIH M01‐RR07122), the Wake Forest Clinical and Translational Science Award (NIH UL1 TR001420), and Forsyth Medical Center and Wake Forest School of Medicine Department of Pediatrics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine.

We report a case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine (CBZ). CBZ, an antiepileptic drug, is known to cause hyponatremia. The mechanism is generally considered to be inappropriate secretion of antidiuretic hormone, whereas an experimental study suggests a direct effect of CBZ on the kidney by stimulating vasopressin receptor. An 18-year-old male with atypical autism and epilepsy has been treated with CBZ and clobazam since age 9 and 10years, respectively. At age 11, he was found to have asymptomatic hyponatremia. He had the habit of drinking tea approximately 3L/day. The low plasma osmolality and high urine osmolality and sodium concentration in the presence of normal thyroid and adrenal function were compatible with syndrome of inappropriate excretion of antidiuretic hormone. His plasma vasopressin level, however, was undetectable. Urine cyclic AMP level was higher than expected from urine osmolality despite the suppressed plasma arginine vasopressin. With fluid restriction, hyponatremia improved. CBZ tapering begun later in the course maintained normal serum sodium concentrations with less strict water intake. This case demonstrates the direct effect of CBZ stimulating vasopressin receptor in the kidney leading to nephrogenic syndrome of inappropriate diuresis.

Can Quantab titrator sticks reliably predict urinary sodium?

Urinary sodium concentration is a commonly used marker for extracellular fluid depletion which is often associated with dehydration. A point of care test for urinary sodium may reduce delays in clinical decision making by offering more timely guidance leading to improved salt and fluid management. We compared laboratory assessed urinary sodium with a potential point of care measure of urinary chloride in a variety of in- and outpatient specialities, to explore its use as an indicator of low urine sodium. Urinary chloride concentrations were estimated using a Quantab titrator stick in samples from patients that had been sent for urinary sodium assays. We validated the results of this titrator stick with laboratory-assessed sodium concentrations by deriving correlation coefficients between these methods and using limits of agreement testing. We determined the optimal titrator stick cut-point for identifying low urinary sodium (urinary sodium <20 mmol/L) by maximising the product of the sensitivity and specificity. This level of urinary sodium was used to mirror the British Society of Gastroenterology guidance on short bowel patients Nightingale and Woodward, 2006. We obtained laboratory urinary sodium concentration and Quantab stick chloride measures on 127 samples. Twenty three percent had a urinary sodium below 20 mmol/L so were regarded as biochemically dehydrated. A threshold of <4.3 on the Quantab scale had a positive predictive value for low sodium of 56% (95%CI 40%-71%) and a negative predictive value of 94% (95%CI 87%-98%). These data suggest that the Quantab stick could be used as a point of care test to aid fluid and salt management decisions in an outpatient setting. Further work to explore the use of the titrator stick in specific patient populations at risk of salt and water depletion is justified.

Sodium Intake Requirements for Preterm Neonates: Review and Recommendations.

It is widely accepted that sodium is an essential nutritional electrolyte and its deficiency is associated with neurological sequelae and poor growth. The provision of an adequate sodium intake to preterm neonates is hampered by the technical difficulty in clinically assessing total body sodium content. As addressed in this review, there is a lack of consensus on the definition of hyponatremia early in life, but there is no evidence that it should deviate from the widely accepted normative data for adult subjects. A low urinary sodium content is accepted by many as reflecting total body sodium deficiency, yet spot urinary sodium measurements are of questionable clinical value. The hormonal regulation of sodium homeostasis is here reviewed and the mechanism accounting for sodium deficiency-induced growth impairment in preterm infants addressed. Lastly, we provide evidence-based gestational and postnatal age-dependent recommendations for the provision of adequate sodium intake to preterm neonates.

Simple blood and urinary parameters measured at ICU admission may sign for AKI development in the early postoperative period: a retrospective, exploratory study

Recent studies have suggested that some blood physicochemical and urinary biochemical parameters have a standardized behavior during acute kidney injury (AKI) development. The changes in these parameters frequently begin to occur before significant rises in serum creatinine (sCr) and may help in identifying patients with more subtle decreases in glomerular filtration rate (GFR). Surgical patients have an increased risk of AKI but renal impairment is usually not evident at ICU admission. We hypothesized that the surgical patients who have AKI diagnosed in the early postoperative period have an impaired GFR since ICU admission, indirectly inferred by alterations in these blood physicochemical and urinary biochemical parameters even in the presence of a still normal sCr. We retrospectively evaluated 112 surgical patients who were categorized according to AKI development during the first 3 ICU days. Twenty-eight patients developed AKI, most of them in the first day (D1) after ICU admission (D0). AKI patients had, at D0, lower serum pH and albumin, higher C - reactive protein (CRP), lower urine sodium (NaU) and fractional excretion of urea (FEUr). Fractional excretion of potassium (FEK) was high in both groups at D0 but remained high in the subsequent days only in AKI patients. Very low CRP and high serum albumin, high NaU and FEUr values at ICU admission had a significant negative predictive value for AKI. We concluded that some easily assessed parameters in blood and urine may help to identify patients with indirect signs of increased inflammatory response and decreased GFR at ICU admission, which could help to predict the risk of postoperative AKI development.

Abstract 12930: Low Urine Sodium (UNa) Early After Heart Failure Admission Predicts Long Length of Stay and Early Mortality

Background: Although decongestion is the primary focus of acute heart failure (HF) management, the degree of natriuretic response to diuretic therapy varies and may predict length of stay (LOS) and early outcomes. We hypothesize that a UNa &amp;lt60 mmol/L, measured after initial intravenous (IV) diuretic administration, would be associated with longer duration of IV diuretic, longer LOS, increased use of inotropic therapy in hospital and higher risk of death. Methods and Results: From July 1, 2014-May 30, 2015, we enrolled 100 unique patients hospitalized to the advanced HF service for decompensated HF. Dose of IV diuretic was based on their daily oral home dose. Spot urine samples were collected within a median of 98 (0-187) minutes after initial diuretic therapy. Patients with UNa &amp;lt60 mmol/L (n=30) had significantly lower serum sodium and higher admission NT-proBNP than those with UNa &amp;gt60 mmol/L (n=70). As well, they were more commonly rated with hemodynamic profile C (“cold and wet”, 40.0 vs.11.4%, p=0.002) and INTERMACS profile 3-4 (30.0 vs. 12.9%, p= 0.04). During the hospital stay, patients with low initial UNa required longer use of IV diuretic therapy (9.5 vs. 5.0 days, p&amp;lt0.0001) and had a longer median LOS (12.0 vs. 6.0 days, p&amp;lt 0.0001) than those with high UNa. After adjusting for eGFR, UNa &amp;lt60 mmol/L was still associated with a higher likelihood of inotropic usage in hospital (hazard ratio [HR] 9.91 (3.27-30.05); p&amp;lt0.0001) and death (HR 3.14 (1.20-8.23); p=0.004) at a median follow-up period of 85 (38-159) days (figure 1). Conclusions: Low UNa after initial IV diuretic administration identifies a population of acute HF patients with advanced disease who have longer LOS and are at high risk for death. Measurement of UNa after first diuretic therapy may help to facilitate triage of patients with heart failure and anticipate the need for advanced HF therapies

Relationship of 24-h urinary sodium excretion with blood pressure, arterial distensibility, and urine albumin in Chinese hypertensive patients

Aims The aim was to determine the relationship of salt intake with blood pressure, arterial distensibility, and microalbuminuria in Chinese hypertensive patients. Methods and results We recruited 341 hypertensive patients who were not on antihypertensive treatment. Blood pressure, 24-h urinary sodium, microalbuminuria, and brachial–ankle pulse wave velocity (baPWV) were measured in these patients. The patients were divided into three groups based on the 24-h urinary sodium excretion: Group A, low urinary sodium excretion (<100 mmol/24 h); Group B, medium urinary sodium excretion (≥100 and<200 mmol/24 h); and Group C, high urinary sodium excretion (≥200 mmol/24 h). Multivariate linear regression was used to analyse the relationship of 24-h urinary sodium excretion with blood pressure, arterial distensibility, and urine albumin. The 24-h urinary sodium excretion levels in Groups A, B, and C were 78.6 ± 17.9, 146.7 ± 26.9, and 254.7 ± 41.8 mmol/24 h, respectively. The baPWV was significantly higher in Group C than in Group A (1753.5 ± 303.8 vs. 1604.9 ± 339.9 cm/s, P = 0.028). In addition, blood pressure and microalbuminuria levels were significantly higher in Group C than in Group A ( P < 0.001 and P = 0.008, respectively). Multivariate regression analysis revealed that 24-h urinary sodium excretion was associated with baPWV ( P = 0.021) and microalbuminuria ( P = 0.027). Conclusion High salt intake correlated with an increase in blood pressure and urine albumin and a decrease in arterial distensibility in Chinese hypertensive patients.

CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study.

Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

Renal Sodium Handling in Children with Nephrotic Syndrome

Background and Objectives: Neprhrotic Syndrome (NS) is a predictable complex with severe, prolonged increase in glomerular permeability for protein leading to hypo-albuminemia. Edema is the other major abnormality; but the underlying mechanism is incompletely resolved. Again during edema formation stage, some of these children express clinical symptoms of hypovolemia, while others do not. The purpose of the study was to identify the NS-children with hypovolemia by measuring the parameters of renal function in respect to their specificity and easy availability.&#x0D; Methods: We studied renal function in 17 children with NS in full blown nephrosis who had come to the Nephrology-Follow up Clinic or the OPD in Dhaka Shishu (Children) Hospital (DSH) and got admitted into the hospital as nephrotic patients with relapses or 1st episodes. The period of study was July 2001 to December 2001 for total period of 6 months. Findings were related to presence or absence of symptoms suggestive of hypovolemia, and were compared to results of similar studies in the same children in remission.&#x0D; Results: Nine children presented with hypovolemic symptoms, and 8 without such symptoms. Both groups displayed severe proteinuria, hypo-albuminemia and edema. Twelve (70.5%) children showed higher blood pressure values in comparision to those of remission. Symptomatic patients showed tendency for a low glomerular filtration rate (GFR), and significantly impaired urine dilution, lower urine-sodium (UNa/Ucr), decreased fractional sodium excretion (FENa), and elevated sodium-potassium exchange quotient, UK/(UK+UNa). In the non-symptomatic patients, these parameters were normal.&#x0D; Conclusions: Among parameters of renal functions,UK/(UK+UNa)-sodium-potassium exchange quotient was found to be the most specific - higher values in hypovolemic patients and lower in patients with stable edema, and in remission too.&#x0D; Ibrahim Cardiac Med J 2013; 3(1&amp;2): 15-20

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass

High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.

A Curious Case of a Rapid Resolution of Acute Tubular Necrosis After Portal Vein Decompression in a Cirrhotic Patient With Underlying Hepatorenal Syndrome: A Case Report and Literature Review

Introduction: Acute kidney injury is a common complication in cirrhosis and is associated with a poor prognosis. Splanchnic vasodilatation triggered by portal hypertension with subsequent renal vasoconstriction appears to play a central role in the hemodynamic changes and the decline in renal function in cirrhotic patients. We report a case of a 54-year-old female with decompensated alcoholic cirrhosis and underlying type 2 hepatorenal syndrome (HRS) based on a low urine sodium and bland urinalysis, who presented with confusion and abdominal pain. Abdominal duplex ultrasound revealed acute non-occlusive portal and superior mesenteric vein thrombosis with increased portal pressure. The patient subsequently developed acute tubular necrosis (ATN) with a serum creatinine of 4.0 mg/dL from a baseline of 0.9 mg/dL. The diagnosis was made based on high urine sodium and the presence of urinary granular cast. Due to worsening renal function, hemodialysis was initiated. Mechanical thrombectomy of the superior mesenteric and portal vein thrombus was performed with a substantial decrease of portal pressure. Her renal function recovered significantly and returned to baseline 4 days after the procedures. In conclusion, a rise in portal pressure from extensive portal vein thrombosis in this case led to the profound renal hypoperfusion and worsening of HRS which led to ATN. Thus, decompression of portal hypertension and reversal of hemodynamics using TIPS and mechanical thrombectomy might have beneficial effects in other cirrhotic patients with similar presentation. Further studies are warranted to prove this theory.Figure 1Figure 2

Prevalence and Nutritional Status of Infants With Cystic Fibrosis and Pseudo-Bartter Syndrome During the First Year of Life

Background. Cystic fibrosis (CF) is an autosomal recessive disease more commonly occurring among Caucasians. An electrolyte derangement, pseudo-Bartter syndrome (PBS) is a complication leading to failure to thrive. Objectives. To describe the prevalence of PBS and related nutritional status in infants with CF detected after a newborn screening test who were treated in a Brazilian town with a very warm climate. Methods. This was a retrospective study with data collected from medical records. The diagnosis of PBS was based on hypokalemia (K+ &lt; 3.5 mEq/L), hyponatremia (Na++ &lt; 135 mEq/L), low urinary sodium (Na++ &lt; 20 mEq/L), and metabolic alkalosis (pH &gt; 7.45; bicarbonate &gt;28 mEq/L). The anthropometric data assessed were weight and length at the following: birth, diagnosis of CF, diagnosis of PBS, and discharge from hospital after correction of PBS and at 12 months of age. The nutritional indicators were weight/height, weight/age, length/age, and body mass index/age ratios. The cutoff point was z-score &lt; p −2 (World Health Organization reference). Data were analyzed using the Anthro (World Health Organization) and Epi-info 2007 programs. Results. Twelve infants with CF were included, and 41.6% (5) had PBS. There was progressive improvement of nutritional status after CF management and after an early diagnosis and management of PBS. Conclusions. The prevalence of PBS was high. There were mild clinical manifestations of PBS accompanied by compromised nutritional status, identified in patients from a region of hot weather.

The balance of cortisol–cortisone interconversion is shifted towards cortisol in neonates with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

BackgroundPatients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an impaired cortisol synthesis, but it is unknown whether the metabolism of glucocorticoids differs between neonates and infants with and without 21OHD. ObjectiveThe objective of this study was to compare the glucocorticoid metabolism between neonates and infants with and without 21OHD. MethodsWe analyzed 14 urinary glucocorticoid metabolites, 7 metabolites each of cortisol and cortisone, by gas chromatography–mass spectrometry of 89 untreated 21OHD neonates and infants and 161 neonates and infants without 21OHD. ResultsNeonates with 21OHD exhibit elevated relative amounts of cortisol metabolites in total glucocorticoid metabolism and an increased ratio of cortisol to cortisone metabolites (p<0.0001). This reflects a shift toward cortisol in the relative balance of the interconversion between cortisol and cortisone. The ratio of cortisol to cortisone metabolites correlated significantly with low urinary glucocorticoid concentrations (p<0.03), with low 21-hydroxylase activity (p<0.001) and high urinary sodium and chloride concentrations (p<0.05) in neonates with 21OHD. ConclusionsOur results demonstrate substantial changes in the relative cortisone to cortisol interconversion in neonates with 21OHD. The shift of glucocorticoid metabolism toward active cortisol in neonates with 21OHD seems to be related to the severity of 21OHD and adrenal dysfunction. Our data provide new insights into the regulation of glucocorticoid homeostasis in 21OHD.

Insufficient Natriuretic Response to Continuous Intravenous Furosemide Is Associated With Poor Long-Term Outcomes in Acute Decompensated Heart Failure

BackgroundTreatment of acute decompensated heart failure (ADHF) with loop diuretics, such as furosemide, is frequently complicated by insufficient urine sodium excretion. We hypothesize that insufficient natriuretic response to diuretic therapy, characterized by lower urine sodium (UNa) and urine furosemide, is associated with subsequent inadequate decongestion, worsening renal function, and adverse long term events. Methods and ResultsWe enrolled 52 consecutive patients with ADHF and measured serum and urine sodium (UNa), urine creatinine (UCr), and urine furosemide (UFurosemide) levels on a spot sample taken after treatment with continuous intravenous furosemide, and followed clinical and renal variables as well as adverse long-term clinical outcomes (death, rehospitalizations, and cardiac transplantation). We observed similar correlations between UNa:UFurosemide ratio and UNa and fractional excretion of sodium (FENa) with 24-hour net urine output (r = 0.52–0.64, all P < .01) and 24-hour weight loss (r = 0.44–0.56; all P < .01). Interestingly, FENa (but not UNa or UNa:UFurosemide) were influenced by estimated glomerular filtration rate (eGFR). We observed an association between lower UNa:UFurosemide with greater likelihood of worsening renal function (hazard ratio [HR] 3.01; P = .02) and poorer adverse clinical outcomes (HR 1.63, P = .008) after adjusting for age and eGFR. Meanwhile, both diminished weight loss and net fluid output over 24 hours of continuous intravenous furosemide were observed when UNa:UFurosemide ratios were <2 mmol/mg or when UNa <50 mmol. ConclusionIn patients with ADHF receiving continuous furosemide infusion, impaired natriuretic response to furosemide is associated with greater likelihood of worsening renal function and future adverse long-term outcomes, independently from and incrementally with decreasing intrinsic glomerular filtration.

Relationship Between Urinary Sodium Excretion Over Time and Mortality in Type 2 Diabetes

It remains unclear whether dietary salt intake over years (not just at baseline) influences hard outcomes. We have previously demonstrated an increased risk of mortality in patients with type 2 diabetes (T2D) and low baseline 24-h urinary sodium excretion (24hUNa) (1). Based on the same cohort of patients, the aim of the current study was to examine the relationship among serial measurements of 24hUNa, estimated glomerular filtration rate (eGFR), and all-cause mortality, adjusting for covariates associated with 24hUNa and eGFR. This was a prospective cohort study of patients with T2D attending a single tertiary hospital diabetes clinic, initiated in mid-2000 with follow-up completed in 2010 (1). Serial 24hUNa (mmol/24 h) and eGFR (mL/min/1.73 m2) measurements were performed at regular intervals. The impact of 24hUNa and eGFR over time on all-cause mortality was determined by a joint model of longitudinal (linear-mixed model) and time-to-event (Weibull parametric survival model) data. Follow-up 24hUNa and eGFR data from 588 patients were used in the current analysis. There were 152 deaths …

High age and low sodium urine concentration are associated with poor survival in patients with hepatorenal syndrome

Background. Combination therapy with terlipressin and albumin substitution is considered a widely accepted treatment regimen for patients with hepatorenal syndrome (HRS). However, only half of the patients respond to treatment and to date albumin substitution and terlipressin therapy are among the most expensive medical treatments available for patients with liver diseases. Thus, we aimed to identify clinical and etiological parameters to predict treatment response and overall mortality in patients with HRS.Material and methods. We retrospectively evaluated 21 patients, 13 male/8 female, aged 43-72 years with HRS. Four patients were transplanted after following combination treatment. Terlipressin was administered by continuous intravenous perfusion (2–6 mg/d) and albumin drips (50 mg) were given daily. Treatment response was defined by a decrease in serum creatinine level to < 1.5 mg/dL or by a > 50% reduction of the baseline concentration.Results. 57% of the patients responded to treatment, which was associated with improved survival at day 60, compared to non-responders. However, the overall mortality was not different between the two groups. Median age of 63 years was a significant negative predictor for therapy response. High baseline urinary sodium levels were of prognostic value for survival. The Model of End stage Liver Disease score (MELD score) did not correlate with therapy response.Conclusion. In conclusion high age is a predictor of non-response. Low urinary sodium before treatment is associated with poor survival. Terli-pressin and albumin co-treatment is associated with increased two-months survival rate. This seemingly moderate extension in survival rate can, however, be decisive for obtaining liver transplantation.

Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators.

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.

Food and nutrient intakes and their associations with lower BMI in middle-aged US adults: the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP)

Clinical trial data show that reduction in total energy intake enhances weight loss regardless of the macronutrient composition of the diet. Few studies have documented dietary patterns or nutrient intakes that favor leanness [BMI (in kg/m²) ≤25] in free-living populations. This investigation examined associations of usual energy, food, and nutrient intakes with BMI among US participants of the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). The INTERMAP is an international cross-sectional study of dietary factors and blood pressure in men and women (ages 40-59 y) that includes 8 US population samples. The present study included data from 1794 Americans who were not consuming a special diet and who provided four 24-h dietary recalls and 2 timed 24-h urine collections. Multivariable linear regression with the residual method was used to adjust for energy intake; sex-specific associations were assessed for dietary intakes and urinary excretions with BMI adjusted for potential confounders including physical activity. Lower energy intake was associated with lower BMI in both sexes. Univariately, higher intakes of fresh fruit, pasta, and rice and lower intakes of meat were associated with lower BMI; these associations were attenuated in multivariable analyses. Lower urinary sodium and intakes of total and animal protein, dietary cholesterol, saturated fats, and heme iron and higher urinary potassium and intakes of carbohydrates, dietary fiber, and magnesium were associated with lower BMI in both sexes. The consumption of foods higher in nutrient-dense carbohydrate and lower in animal protein and saturated fat is associated with lower total energy intakes, more favorable micronutrient intakes, and lower BMI.