Urinary Chloride Concentrations Research Articles

Association between urinary chloride excretion and progression of coronary artery calcification in patients with nondialysis chronic kidney disease: results from the KNOW-CKD study.

Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC). A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period. Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190-0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios. High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

Electrochemical Sensing of Urinary Chloride Ion Concentration for Near Real-Time Monitoring.

Urinary chloride concentration is a valuable health metric that can aid in the early detection of serious conditions, such as acid base disorders, acute heart failure, and incidences of acute renal failure in the intensive care unit. Physiologically, urinary chloride levels frequently change and are difficult to measure, involving time-consuming and inconvenient lab testing. Thus, near real-time simple sensors are needed to quickly provide actionable data to inform diagnostic and treatment decisions that affect health outcomes. Here, we introduce a chronopotentiometric sensor that utilizes commercially available screen-printed electrodes to accurately quantify clinically relevant chloride concentrations (5-250 mM) in seconds, with no added reagents or electrode surface modification. Initially, the sensor's performance was optimized through the proper selection of current density at a specific chloride concentration, using electrical response data in conjunction with scanning electron microscopy. We developed a unique swept current density algorithm to resolve the entire clinically relevant chloride concentration range, and the chloride sensors can be reliably reused for chloride concentrations less than 50 mM. Lastly, we explored the impact of pH, temperature, conductivity, and additional ions (i.e., artificial urine) on the sensor signal, in order to determine sensor feasibility in complex biological samples. This study provides a path for further development of a portable, near real-time sensor for the quantification of urinary chloride.

Estimation of Plasma Renin Activity on the Basis of Serum and Urinary Chloride Concentrations versus Sodium Concentrations

Introduction: The present study examined the possible estimation of plasma renin activity (PRA) by serum and urinary concentrations of chloride versus sodium in acute and chronic heart failure (HF). Methods: Data from 29 patients with acute HF (48% men; 80.3 ± 12 years) and 26 patients with recovery of HF after decongestive therapy (50% men; 81.2 ± 12 years) were analyzed. Blood and urine samples were obtained immediately before decongestive therapy in acute HF patients. Clinical tests included peripheral blood tests, serum and spot urinary electrolytes, and plasma neurohormones. Sodium- or chloride-related indices included serum ([sNa⁺] or [sCl⁻]) and urinary ([uNa⁺] or [uCl⁻]) concentrations, their differences, and their ratio. Linear regression analysis was used for correlation coefficients. Results: PRA levels higher than the normal range were detected in only 5 (17%) of 29 patients with acute HF, but in as many as 11 (42%) of 26 patients with chronic HF. In the 29 patients with acute HF, all the chloride- and sodium-related indices except for [sNa⁺] were correlated with PRA: the [sCl⁻]/[uCl⁻] ratio was best correlated with PRA (R² = 0.84, p < 0.0001) followed by the [sNa⁺]/[uNa⁺] ratio (R² = 0.64, p < 0.0001). In the 26 patients with chronic HF, however, both the [sCl⁻] (R² = 0.36, p = 0.001) and [sNa⁺] (R² = 0.22, p = 0.016) were only weakly correlated with PRA. Conclusion: In acute HF, chloride-related indices derived from serum and urinary concentrations were firmly associated with PRA or better than sodium-related indices. In chronic HF, either chloride- or sodium-related indices were not firmly associated with PRA, presumably due to influence of cardiovascular medication.

Urinary Chloride Excretion Postcardiopulmonary Bypass in Pediatric Patients-A Pilot Study.

The aim of this study was to describe renal chloride metabolism following cardiopulmonary bypass (CPB) surgery in pediatric patients. A prospective observational trial in a tertiary pediatric intensive care unit (PICU) with 20 recruited patients younger than 2 years following CPB surgery was conducted. Urinary electrolytes, plasma urea, electrolytes, creatinine, and arterial blood gases were collected preoperatively, on admission to PICU and at standardized intervals thereafter. The urinary and plasma strong ion differences (SID) were calculated from these results at each time point. Fluid input and output and electrolyte and drug administration were also recorded. Median chloride administration was 67.7 mmol/kg over the first 24 hours. Urinary chloride (mmol/L; median interquartile range [IQR]) was 30 (19, 52) prior to surgery, 15 (15, 65) on admission, and remained below baseline until 24 hours. Plasma chloride (mmol/L; median [IQR]) was 105 (98, 107) prior to surgery and 101 (101, 106) on admission to PICU. It then increased from baseline, but remained within normal limits, for the remainder of the study. The urinary SID increased from 49.8 (19.1, 87.2) preoperatively to a maximum of 122.7 (92.5, 151.8) at 6 hours, and remained elevated until 48 hours. Plasma and urinary chloride concentrations were not associated with the development of acute kidney injury. Urinary chloride excretion is impaired after CPB. The urinary SID increase associated with the decrease in chloride excretion suggests impaired production and/or excretion of ammonium by the nephron following CPB, with gradual recovery postoperatively.

Transgenic Mice Overexpressing Human Alpha-1 Antitrypsin Exhibit Low Blood Pressure and Altered Epithelial Transport Mechanisms in the Inactive and Active Cycles.

Human alpha-1 antitrypsin (hAAT) is a versatile protease inhibitor, but little is known about its targets in the aldosterone-sensitive distal nephron and its role in electrolyte balance and blood pressure control. We analyzed urinary electrolytes, osmolality, and blood pressure from hAAT transgenic (hAAT-Tg) mice and C57B/6 wild-type control mice maintained on either a normal salt or high salt diet. Urinary sodium, potassium, and chloride concentrations as well as urinary osmolality were lower in hAAT-Tg mice maintained on a high salt diet during both the active and inactive cycles. hAAT-Tg mice showed a lower systolic blood pressure compared to C57B6 mice when maintained on a normal salt diet but this was not observed when they were maintained on a high salt diet. Cathepsin B protein activity was less in hAAT-Tg mice compared to wild-type controls. Protein expression of the alpha subunit of the sodium epithelial channel (ENaC) alpha was also reduced in the hAAT-Tg mice. Natriuretic peptide receptor C (NPRC) protein expression in membrane fractions of the kidney cortex was reduced while circulating levels of atrial natriuretic peptide (ANP) were greater in hAAT-Tg mice compared to wild-type controls. This study characterizes the electrolyte and blood pressure phenotype of hAAT-Tg mice during the inactive and active cycles and investigates the mechanism by which ENaC activation is inhibited in part by a mechanism involving decreased cathepsin B activity and increased ANP levels in the systemic circulation.

Clinical Significance of Spot Urinary Chloride Concentration Measurements in Patients with Acute Heart Failure: Investigation on the Basis of the ‘TubuloGlomerular Feedback’ Mechanism

Urinary chloride (Cl) is the key electrolyte for regulating renin secretion at the macula densa under the ‘tubulo-glomerular feedback’. Whether or not Cl filtrated into the urinary tubules actually associates with plasma renin activity (PRA) in clinical heart failure (HF) remains unclear. Data from 29 patients with acute worsening HF (48% men; 80.3±12 years) were analyzed. Blood and urine samples were immediately obtained before decongestive therapy after the patients rested in a supine position for 20-min. Clinical tests included peripheral blood tests, serum and spot urinary electrolytes, b-type natriuretic peptide (BNP), plasma neurohormones, and fractional urinary electrolyte excretion. In the 29 patients, urinary Cl concentrations inversely correlated with logarithmically transformed PRA (R2 =0.41, p=0.0002). The correlation was weaker in worsening chronic HF patients (R2 =0.32, p=0.01) compared with de novo HF patients (R2 =0.70, p=0.0026). Patients were divided into 2 groups according to the median urinary Cl concentration, a low group and a high group. Compared with the high group (100~184 mEq/L; n=14), the low group (4~95 mEq/L; n=15) exhibited more renal (serum creatinine; 1.45±0.63 vs 1.00±0.38 mg/d, p=0.029) and cardiac (log BNP; 2.99±0.3 vs 2.66±0.32 pg/mL, p=0.008 p=0.008) impairment, and higher PRA (3.42±4.7 vs 0.73±0.46 ng/mL/h, p=0.049), and lower fractional excretion of urinary Cl (1.34±1.3 vs 5.33±4.1%, p&lt;0.0001). The present study provides clinical data on the possible functioning of urinary Cl involved in the mechanism of ‘tubulo-glomerular feedback’, and thus advances our understanding of the clinical meanings of the significance of urinary Cl concentration measurement.

Clinical Significance of Spot Urinary Chloride Concentration Measurements in Patients with Acute Heart Failure: Investigation on the Basis of the ‘TubuloGlomerular Feedback’ Mechanism

Urinary chloride (Cl) is the key electrolyte for regulating renin secretion at the macula densa under the ‘tubulo-glomerular feedback’. Whether or not Cl filtrated into the urinary tubules actually associates with plasma renin activity (PRA) in clinical heart failure (HF) remains unclear. Data from 29 patients with acute worsening HF (48% men; 80.3±12 years) were analyzed. Blood and urine samples were immediately obtained before decongestive therapy after the patients rested in a supine position for 20-min. Clinical tests included peripheral blood tests, serum and spot urinary electrolytes, b-type natriuretic peptide (BNP), plasma neurohormones, and fractional urinary electrolyte excretion. In the 29 patients, urinary Cl concentrations inversely correlated with logarithmically transformed PRA (R2 =0.41, p=0.0002). The correlation was weaker in worsening chronic HF patients (R2 =0.32, p=0.01) compared with de novo HF patients (R2 =0.70, p=0.0026). Patients were divided into 2 groups according to the median urinary Cl concentration, a low group and a high group. Compared with the high group (100~184 mEq/L; n=14), the low group (4~95 mEq/L; n=15) exhibited more renal (serum creatinine; 1.45±0.63 vs 1.00±0.38 mg/d, p=0.029) and cardiac (log BNP; 2.99±0.3 vs 2.66±0.32 pg/mL, p=0.008 p=0.008) impairment, and higher PRA (3.42±4.7 vs 0.73±0.46 ng/mL/h, p=0.049), and lower fractional excretion of urinary Cl (1.34±1.3 vs 5.33±4.1%, p&lt;0.0001). The present study provides clinical data on the possible functioning of urinary Cl involved in the mechanism of ‘tubulo-glomerular feedback’, and thus advances our understanding of the clinical meanings of the significance of urinary Cl concentration measurement.

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.

Differential diagnosis of perinatal Bartter, Bartter and Gitelman syndromes.

The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome (BS) must be considered in idiopathic early-onset polyhydramnios. Fetal megabladder in BS may allow its distinction from third-trimester polyhydramnios that occurs in congenital chloride diarrhea (CCD). Fetal megacolon occurs in CCD while fecal chloride >90 mEq/L in infants is diagnostic. Failure-to-thrive, polydipsia and polyuria in early childhood are the hallmarks of classic BS. Unlike BS, there is low urinary chloride in hypokalemic alkalosis of intractable emesis and cystic fibrosis. Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency. Acquired BS may result from calcimimetic up-regulation of a calcium-sensing receptor or autoantibody inactivation of sodium chloride co-transporters in Sjögren syndrome. A relatively common event of heterozygous gene mutations for Gitelman syndrome increases the likelihood of its random occurrence in certain diseases of adult onset. Finally, diuretic abuse is the most common differential diagnosis of SLT. Unlike the persistent elevation in BS, urinary chloride concentration losses waxes and wanes on day-to-day assessment in patients with diuretic misuse.

Electrolyte-based calculation of fluid shifts after infusing 0.9% saline in severe hyperglycemia

BackgroundEarly treatment of severe hyperglycemia involves large shifts of body fluids that entail a risk of hemodynamic instability. We studied the feasibility of applying a new electrolyte equation that estimates the degree of volume depletion and the distribution of infused 0.9% saline in this setting.MethodsThe new equation was applied to plasma and urinary concentrations of sodium and chloride measured before and 30 min after a 30-min infusion of 1 L of 0.9% saline on two consecutive days in 14 patients with severe hyperglycemia (mean age 50 years). The extracellular fluid (ECF) volume was also estimated based on the volume dilution kinetics of chloride.ResultsOn day 1, the baseline ECF volume amounted to 11.5 L. The saline infusion expanded the ECF space by 160 mL and the intracellular fluid space by 375 mL. On day 2, the ECF volume was 15.5 L, and twice as much of the infused fluid remained in the ECF space. The chloride dilution kinetics yielded baseline ECF volumes of 11.6 and 15.2 L on day 1 and day 2, respectively. No net uptake of glucose to the cells occurred during the two 1-h measurement periods despite insulin administration in the intervening time period.ConclusionsThe electrolyte equation was feasible to apply in a group of hyperglycemic patients. The ECF space was 3 L smaller than expected on admission but normal on the second day. Almost half of the infused fluid was distributed intracellularly.

Urinary chloride concentration and progression of chronic kidney disease: results from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease.

Urinary chloride is regulated by kidney transport channels, and high urinary chloride concentration in the distal tubules can trigger tubuloglomerular feedback. However, little attention has been paid to urinary chloride as a biomarker of clinical outcomes. Here, we studied the relationship between urinary chloride concentration and chronic kidney disease (CKD) progression. We included 2086 participants with CKD from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease. Patients were categorized into three groups, according to baseline urinary chloride concentration tertiles. The study endpoint was a composite of ≥50% decrease in estimated glomerular filtration rate from baseline values, or end-stage kidney disease. During a median follow-up period of 3.4 years (7452 person-years), 565 participants reached the primary endpoint. There was a higher rate of CKD progression events in the lowest and middle tertiles than in the highest tertile. Compared with the lowest tertile, the highest tertile was associated with 33% [95% confidence interval (CI) 0.49-0.90] lower risk for the primary outcome in a cause-specific hazard model after adjustment for confounding variables. In addition, for every 25 mEq/L increase in urinary chloride concentration, there was 11% (95% CI 0.83-0.96) lower risk for CKD progression. This association was consistent in a time-varying model. Urinary chloride concentration correlated well with tubule function and kidney injury markers, and its predictive performance for CKD progression was comparable to that of these markers. In this hypothesis-generating study, low urinary chloride concentration was associated with a higher risk for CKD progression.

Urinary chloride concentration as a prognostic marker in critically ill patients.

Associations have been reported among serum chloride concentration, mortality and incidence of acute kidney injury (AKI) in intensive care units (ICU). This study aimed to examine associations among urinary chloride, mortality, and AKI incidence in ICU patients. A retrospective observational study was conducted among medical-surgical ICU in a tertiary hospital wherein 170 consecutive ICU patients were evaluated from October 2015 to March 2016 and 116 patients were enrolled. Serial data of serum and urine electrolytes from day 1 to day 4 of ICU admission were examined. The primary and secondary outcomes were ICU mortality and incidence of AKI in the ICU, respectively. Among the 116 enrolled patients, 15 (13%) died during their ICU stay. Although serum and urinary sodium and potassium on day 1 did not significantly differ between ICU survivors and non-survivors, urinary chloride concentration on day 1 was significantly lower in non-survivors. Receiver operating characteristic analysis showed that the cutoff value of day 1 urinary chloride concentration for prediction of ICU mortality was 53 mEq/L. The lower urinary chloride concentration group on day 1 showed a significantly lower survival rate, even in long-term follow-up, compared with the higher urinary chloride group. Addition of day 1 urinary chloride concentration improved prediction of AKI incidence in the ICU by Sequential Organ Failure Assessment score alone. Lower urinary chloride concentration was associated with increased mortality and incidence of AKI in the ICU. Further investigation is necessary to clarify the mechanism of urinary chloride regulation.

The effects of chronic acetaminophen exposure on the kidney, gill and liver in rainbow trout (Oncorhynchus mykiss)

In this study, we examined if rainbow trout chronically exposed to acetaminophen (10 and 30 μgL−1) showed histological changes that coincided with functional changes in the kidney, gill and liver. Histological changes in the kidney included movement and loss of nuclei, non-uniform nuclei size, non-uniform cytoplasmic staining, and loss of tubule integrity. Histological effects were more severe at the higher concentration and coincided with concentration dependent increases in urine flow rate and increased urinary concentrations of sodium, chloride, potassium, calcium, urea, ammonia, glucose, and protein. Yet, glomerular filtration rate was not altered with acetaminophen exposure. In the gill, filament end swelling, whole filament swelling, and swelling of the lamellae were observed in exposed fish. Lamellar spacing decreased in both exposure groups, but lamellar area decreased only with 30 μgL−1 exposure. At faster swimming speeds, oxygen consumption was limited in acetaminophen exposed fish, and critical swimming speed was also decreased in both exposure groups. The liver showed decreased perisinusoidal spaces at 10 and 30 μgL−1 acetaminophen, and decreased cytoplasmic vacuolation with 30 μgL−1 acetaminophen. A decrease in liver glycogen was also observed at 30 μgL−1. There was no change in plasma concentrations of sodium, chloride, potassium, calcium, magnesium, and glucose with exposure, suggesting compensation for urinary loss. Indeed, an increase in Na+-K+-ATPase activity in the gills was found with 30 μgL−1 acetaminophen exposure. Chronic exposure of rainbow trout to the environmentally relevant pharmaceutical acetaminophen, alters both histology and function of organs responsible for ion and nutrient homeostasis.

Loop diuretic down-titration in stable chronic heart failure is often achievable, especially when urinary chloride concentration is low

Background: This study investigates spot urinary chloride concentration in euvolemic chronic heart failure (CHF) patients.Methods: This prospective cohort study included 50 ambulatory CHF patients on maintenance loop diuretics without recent hospital admission, clinical signs of volume overload, or adjustment in neurohumoral blocker or diuretic therapy. Spot urinary samples were collected immediately after loop diuretic intake. Subsequently, loop diuretic dose was reduced with 50% or stopped if ≤40 mg furosemide equivalents. Successful down-titration was defined as persistent dose reduction after 7 d without body weight increase >1.5 kg.Results: Urinary chloride concentration was 3045 ± 1271 mg/L overall. Patients with higher versus lower urinary chloride concentrations took the same dose of loop diuretics [40 mg (20–40 mg) furosemide equivalents; p value = .509] and had similar plasma NT-proBNP levels [1179 ng/L (311–2195 ng/L) versus 900 ng/L (255–1622 ng/L), respectively; p value = .461]. Down-titration was successful in 72% versus 76%, respectively (p value = 1.000). At 30 d, loop diuretic dose remained reduced in 59% versus 76% of patients, respectively (p value = .238). The proportion of patients free from diuretic therapy was 45% versus 62% in the high versus low chloride concentration group (p value = .265).Conclusions: Loop diuretic down-titration was successful in 3 out of 4 euvolemic CHF patients, irrespectively of urinary chloride concentration on spot samples collected after diuretic intake.

Alibertia edulis (L.C. Rich.) A.C. Rich – A potent diuretic arising from Brazilian indigenous species

Ethnopharmacological relevanceAlthough Alibertia edulis (L.C. Rich.) A.C. Rich decoction is used in Brazilian folk medicine due to its possible antihypertensive effect, this species has never been critically investigated as a hypotensive drug. So, the aim of this study was to evaluate the possible hypotensive and antihypertensive effects of the oral administration of Alibertia edulis aqueous extract (AEAE) in normotensive and hypertensive rats, and evaluate its inter-relation with a possible diuretic activity. Material and methodsDifferent doses of AEAE (20, 65 and 200mg/kg) were tested on the mean arterial pressure (MAP) of normotensive Wistar rats and after induction of renovascular hypertension (two-kidney, one-clip Goldblatt model). In addition, the diuretic effects of AEAE were compared with hydrochlorothiazide (HCTZ) in an acute and repeated-dose treatment for 7 days. Volume, sodium, potassium, chloride, calcium contents, pH and density were estimated in urine samples collected after 8 or 24h. Plasma sodium, potassium, total protein, urea, creatinine, AST and ALT concentrations were measured in samples collected at the end of the experimental period (seventh day). Finally, the antioxidant activity of the AEAE was assessed using the DPPH radical scavenging and ferric ions reducing power assay. ResultsThe intraduodenal administration of the HCTZ and AEAE significantly reduced, in a dose-dependent manner, the MAP in both normotensive and hypertensive rats. Otherwise, the heart rate was not affected by any treatment. Acute and prolonged oral administration of AEAE (200mg/kg) and HCTZ caused a significant increase in volume and urinary concentrations of sodium, potassium and chloride. Moreover, urinary calcium concentration was significantly increased after administration of AEAE (200mg/kg). Finally, AEAE was able to present important in vitro antioxidant properties. ConclusionThe results obtained have shown that AEAE presents potent diuretic activity and significant hypotensive and antihypertensive effect. In addition, this study may confirm part of the pharmacological activity popularly attributed to this species and opens perspective for the future use in various renal and cardiovascular diseases.

Clinical features and SLC26A3 genetic mutation analysis of a kindred with congenital chloride diarrhea

Objective To analyze the clinical characteristics and mutation of SLC26A3 gene of a patient with congenital chloride diarrhea in order to deepen the understanding of the disease. Methods The clinical data of the patient who was admitted in Affiliated Hospital of Capital Pediatric Institute in June 2014 were collected. Venous blood of the proband and his parents (2 mL for each) had been extracted for genomic DNA isolation.The 21 exons of SLC26A3 gene were amplified with polymerase chain reaction and screened for mutations by sequencing. Results The main cli-nical features of the patient included polyhydramnios, preterm, normal birth weight, watery diarrhea, low weight and severe electrolyte disturbances with hypochloremia, hypokalemia, hyponatremia and metabolic alkalosis.Renin angiotensin and aldosterone were high.His urine chloride concentration was low and fecal chloride concentration was high (>90 mmol/L). After oral salt substitution therapy with KCl and NaCl [3 mmol/(kg·d), 4 mmol/(kg·d)], the electrolyte was better, alkalosis was alleviated, and growth and development were improved.The gene analysis revealed that the patient carried nt1631T>A homozygous mutation on exon 15 which lead to Ile544Asn mutation in the predicted SLC26A3 transmembrane protein sequence, which was considered to be responsible for the functional abnormality of the Cl-/HCO3- protein.His parents were carriers of SLC26A3 gene and their clinical phenotype was normal. Conclusions Congenital chloride diarrhea is a rare autosomal recessive disorder and easily misdiagnosed.The patient of early postnatal diarrhea with persistent hypochloremia, hypokalemia, hyponatremia and metabolic alkalosis should be thought about this disease.Genetic analysis can help make the diagnosis.The prognosis is good if a patient has an early diagnosis and appropriate management. Key words: Congenital chloride diarrhea; Metabolic alkalosis; SLC26A3 gene

Diuretic activity of different extracts of Biophytum sensitivum (Linn.) DC.

Introduction:Drugs that induce diuresis are known as diuretics. Diuretic drugs act either by increasing the glomerular filtration rate (or) by decreasing the rate of reabsorption of fluid from the tubules. In recent years, interest in herbal agents as therapeutic treatment option has increased due to their limited side effects.Aim:To evaluate the diuretic activity of various extracts of whole plant of Biophytum sensitivum (Linn.) DC. in Wistar strain albino rats.Materials and Methods:Randomly selected animals were divided into five groups (n = 6 in each). First group served as a control group. Group 2 served as standard control in which furosemide was administered at a dose of 10 mg/kg. Groups 3–5 as test drug groups, in which chloroform, methanol, and aqueous extracts of B. sensitivum were administered orally at a dose of 200 mg/kg. The diuretic activity was evaluated by determination of urine volume and urinary electrolyte concentrations of sodium, potassium, and chloride ions.Results:Methanol and aqueous extracts significantly increased the urinary output and excretion of electrolyte concentrations of sodium and potassium comparatively better than the standard control, and chloroform extract showed insignificant effect.Conclusion:The study concluded that B. sensitivum possess moderate to significant diuretic activity.

A rare cause of rhabdomyolysis: Gitelman syndrome

Introduction: Gitelman syndrome is a rare and autosomal recessive disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and hypertension. A careful history, physical examination and determination of urine chloride concentration are important for diagnosis. In this case report, we discuss a patient with hypokalemia and rhabdomyolysis which is diagnosed as Gitelman syndrome.

Urinary composition during decongestive treatment in heart failure with reduced ejection fraction.

The urinary composition, including sodium (Na(+)) and chloride (Cl(-)) concentrations, might provide useful information in addition to urine output during decongestive treatment in heart failure. Consecutive patients with heart failure (n=61), ejection fraction ≤45%, worsening symptoms, and scheduled treatment with intravenous loop diuretics were included. Patients received protocol-driven therapy until complete decongestion, assessed clinically and by echocardiography. Three consecutive 24-hour urinary collections were performed. With 2 mg (1-4 mg), 1 mg (0-2 mg), and 1 mg (0-1 mg) bumetanide administered in bolus during consecutive 24-hour intervals, in addition to combinational diuretic therapy in ≈70% and both oral spironolactone and vasodilators in ≈90%, euvolemia was reached, often within 24 hours. Urine output was higher during the first when compared with the second or third 24-hour interval (2700 versus 1550 or 1375 mL, respectively; P<0.001), but this was no longer significant after correction for diuretic dose (P=0.263), indicating preserved diuretic efficiency during the study. In contrast, urinary Na(+) and Cl(-) excretion both decreased significantly, even after correction for diuretic dose (P=0.040 and 0.004, respectively), leading to decreasing urinary concentrations with progressive decongestion. After reaching euvolemia, lower urinary Na(+)/Cr and Cl(-)/Cr ratios were both associated with urine output ≤1500 mL (area under the curve, 0.830 and 0.826, respectively; P<0.001 for both), in contrast to plasma N-terminal pro-B-type natriuretic peptide levels that were not (area under the curve, 0.515; P=0.735) CONCLUSIONS: The urinary composition during progressive decongestion in heart failure with reduced ejection fraction is characterized by a drop in urinary Na(+) and Cl(-) concentrations. The urinary Na(+)/Cr or Cl(-)/Cr ratio might provide insightful information to titrate diuretic therapy.

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.