Chloride Excretion Research Articles

A Rare Case Report of Acquired Bartters With Positive Anti Scl70 Antibody

Introduction: Bartter syndrome autosomal recessive renal tubular disorders usualy presents in infant age group or antenatallyCase Description64 years housewife, a known case of hypothyroidism with in emergency with generalized weakness and hypotension. She had an small adrenal nodule work up which showed that it was non functional. On evaluation at time of stress (blood pressure 70/50) her serum cortisol was 300nmol/l and she was therefore started on hydrocortisone. Her records revealed hypokalemia for last 2 years. Workup of hypokalemia showed kaliuresis, metabolic alkalosis, hypercalciuria and excess chloride excretion in the urine, suggestive of bartter’s syndrome. But this needed further confirmation as bartter’s is rare in this age group and also the test was done at the time of stress. She was started on spironolactone and oral potassium supplementation. CECT head done for evaluation of postural dizziness showed chronic cortical venous thrombosis. On follow up ACTH stimulated cortisol was done which showed normal cortisol level so steroid was stopped. She was readmitted one month later with hypokalemia(K-1.8 meq/l) while being on same dosage of spironolactone and potassium. Workup of hypokalemia showed same feature of bartter’s syndrome. Considering the chain of events, a suggestion of bartter’s and response to steroid, a diagnosis of acquired autoimmune bartter’s syndrome along with hypothyroidism was made. An autoimmune work up showed anti SCL 70 positive2+(++). Patient responded to steroid, spironolactone, indomethacin and oral potassium supplementation. Discussion: Bartter’s syndrome can rarely happen in old age too. Seek for autoimmune cause once we suspect acquired bartter’s. To best of our knowledge previously only one case has been reported of acquired Bartter with systemic sclerosis. Patient may develop systemic sclerosis in future as anti SCL70 antibody is very specific for it. It is positive in less than 1 % of general population. Anti SCL70 antibody is rarely positive in Sjogrens syndrome. Our patient did not feature of sjogren or systemic sclerosis even after 4 years follow up

Hacia el esclarecimiento del rol del anión cloruro en la hipertensión arterial: su vínculo con el daño oxidativo en el riñón

Introduction: The role of the chloride anion on the deleterious effects of excessive consumption of salt (NaCl) and whether its effects are independent each other of the presence of sodium remains to date, unknown and unclear. Objective: To demonstrate that both a chloride overload and a sodium overload in the diet produce deleterious effects, by different mechanisms, on systolic blood pressure (SBP), renal function and markers of oxidative stress in the kidney. Materials and Methods: Male Wistar rats were divided into four groups (n = 8 / group) and fed with different diets for three weeks: C: control (standard diet), and diets: NaCl: hypersodic-hyperchloric; Na: hypersodic without chloride and Cl: hyperchloric without sodium. Systolic blood pressure (SBP) and renal function were determined, and the production of thiobarbituric acid reactive species (TBARS) and the activity and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were evaluated in renal cortex tissue. Results: SBP increased (*) in the two groups fed with chloride. The fractional excretion of sodium and chloride increased (*) in the NaCl and Na groups. increased (*) in the renal cortex with the three diets. No changes were observed in the activity and expression of SOD and CAT. GPx activity increased (*) in the two groups that received chloride; (* p <0.05 vs C). Conclusion: Both sodium and chloride overload are associated with a higher oxidative state characterized by an increase in lipid peroxidation in the renal cortex. However, compared with Na group, only chloride overload is associated with higher GPx activity and hypertension without any changes in urinary chloride excretion, suggesting a higher renal pro-oxidant state in this experimental group.

Hacia el esclarecimiento del rol del anión cloruro en la hipertensión arterial: su vínculo con el daño oxidativo en el riñón

Introduction: The role of the chloride anion on the deleterious effects of excessive consumption of salt (NaCl) and whether its effects are independent each other of the presence of sodium remains to date, unknown and unclear. Objective: To demonstrate that both a chloride overload and a sodium overload in the diet produce deleterious effects, by different mechanisms, on systolic blood pressure (SBP), renal function and markers of oxidative stress in the kidney. Materials and Methods: Male Wistar rats were divided into four groups (n = 8 / group) and fed with different diets for three weeks: C: control (standard diet), and diets: NaCl: hypersodic-hyperchloric; Na: hypersodic without chloride and Cl: hyperchloric without sodium. Systolic blood pressure (SBP) and renal function were determined, and the production of thiobarbituric acid reactive species (TBARS) and the activity and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were evaluated in renal cortex tissue. Results: SBP increased (*) in the two groups fed with chloride. The fractional excretion of sodium and chloride increased (*) in the NaCl and Na groups. increased (*) in the renal cortex with the three diets. No changes were observed in the activity and expression of SOD and CAT. GPx activity increased (*) in the two groups that received chloride; (* p <0.05 vs C). Conclusion: Both sodium and chloride overload are associated with a higher oxidative state characterized by an increase in lipid peroxidation in the renal cortex. However, compared with Na group, only chloride overload is associated with higher GPx activity and hypertension without any changes in urinary chloride excretion, suggesting a higher renal pro-oxidant state in this experimental group.

Diuretic Activity of Indian Medicinal Plant: A Review

Diuretics are commonly defined as drugs that increase the amount of urine produced by kidney. A precise definition is that diuretics are the agent which augment the renal excretion of sodium and either chloride or bicarbonate primarily, and water excretion secondarily. The term “saluretic” is sometime used to describe a drug that increase the renal excretion of sodium and chloride ion Diuretics are responsible for increase the rate of urine flow, sodium excretion and to maintain the volume and composition of body fluids in a various clinical Disorders. But drug-induced diuresis is very much beneficial in such type of life-threatening disorders like CHF, hypertension, renal failure, Liver cirrhosis and often pregnancy toxaemia.[1] Diuretics relieve pulmonary congestion and peripheral edema. This decreases cardiac workload, oxygen demand and plasma volume, thus decreasing blood pressure. Thus, diuretics play an important role in hypertensive patients.[2] Plant medicine is commonly used in the traditional treatment of some renal diseases, and many plants are reported to possess significant diuretic activity. The diuretic activity of a number of plants used in ethno medicine as diuretic agents has been confirmed in experimental animal. [3]The progress of a polyherbal formulation is a tough job because of the large number of different chemical compounds present in the different medicinal plants.

P0099 / #613: URINARY CHLORIDE EXCRETION POST-CARDIOPULMONARY BYPASS IN PAEDIATRIC PATIENTS – A PILOT STUDY

Aims & Objectives: Hyperchloraemia and acute kidney injury (AKI) are common following cardiopulmonary bypass (CPB) in paediatric patients. It has not been established whether hyperchloraemia stems from chloride loading or defective chloride excretion. Our study sought to establish patterns of chloride and ammonia metabolism after CPB surgery. Methods: We examined 20 patients under two years, admitted to PICU following CBP surgery. Arterial blood gases, urine electrolytes, urinary strong ion difference, fluid and electrolyte administration, and fluid outputs were recorded pre CPB, on admission and at standardised intervals thereafter. AKI was defined using KDIGO criteria. Results: Urinary Cl (mmol/L;median,[IQR]) was 30[19–52] pre surgery, 15[15–65] on admission, 15[15-38], 20[15-67], 48[15-75] and 120[46-129] at 6,12,24, and 48hours. Serum chloride (mmol/L;median,[IQR]) was 105[98-107] pre surgery, 101[101–106] on admission, and 107[105-110], 109[106-110], 108[105-111] and 107[104-111] at 6,12,24 and 48hours. SIDurine increased from 49.8 to 122.7 at 6hours and dropped to 16 at 48hours. Median chloride administration was 67.7mmol/kg/day in first 24hours. Urinary Cl (mmol/L;median,[IQR]) was 30[19–52] pre surgery, 15[15–65] on admission, 15[15-38], 20[15-67], 48[15-75] and 120[46-129] at 6,12,24, and 48hours. Serum chloride (mmol/L;median,[IQR]) was 105[98-107] pre surgery, 101[101–106] on admission, and 107[105-110], 109[106-110], 108[105-111] and 107[104-111] at 6,12,24 and 48hours. SIDurine increased from 49.8 to 122.7 at 6hours and dropped to 16 at 48hours. Conclusions: Post CPB renal chloride excretion is impaired, despite chloride loading, and increased plasma chloride levels. The SIDUrine increase during the decrease in chloride excretion suggests renal ammonia metabolism is impaired following CPB. Our findings suggest NH4 is crucial in the development of renal impairment post CPB.

Daily Urinary Sodium Excretion Monitoring in Critical Care Setting: A Simple Method for an Early Detection of Acute Kidney Injury.

Introduction:Making an early diagnosis of acute kidney injury (AKI) is crucial. Classical biomarkers are not capable of early detection of AKI, but novel biomarkers that do have this capability are expensive and not universally available. This prospective study attempts to mitigate these limitations through the evaluation of daily urine analysis on patient admitted to a critical care unit in order to detect early AKI.Methods:Daily urinary indices were measured on every patient admitted to the intensive care unit (ICU) from the time of admission until his/her discharge from the ICU or death. This renal monitoring consisted of daily blood and spot morning urine samples in order to measure creatinine, urea, sodium, chloride and potassium in order to calculate the fractional excretion of sodium (FENa), chloride, urea and potassium. The data collected on these patients in the previous days was analyzed to determine whether or not there was a significant statistical difference in the urinary indices one day before the clinical diagnosis of AKI (day – 1) and 2 days before the diagnosis (day – 2). The statistical test applied was a single rank test, using as a limit of significance a value of P < 0.05.Results:Of the 203 patients included, 61 developed AKI. A statistical significant difference was documented only in the value of urinary sodium (UNa) and FENa between day-1 (one day before AKI clinical diagnosis) and day-2 (two days before AKI clinical diagnosis).Conclusion:Daily monitoring of UNa and FENa detected a significant change in their basal values 24 hours before clinical diagnosis of AKI was made.

Association of Renal Glomerular and Tubular Function With Renal Outcome in Patients With Posterior Urethral Valves

ObjectiveTo analyze renal glomerular and tubular function and their association in patients operated for posterior urethral valves and to prognosticate the risk for end-stage kidney disease (ESKD) MethodsSixty-three previously treated patients were evaluated for renal function during 1987-1991. The patients’ age at evaluation was 11 years (range 2-24). Glomerular function was assessed by measuring glomerular filtration rate (GFR) and urine albumin excretion. Tubular function was determined by measuring urine concentration capacity and excretion of electrolytes (Na, K, Cl, Ca, P, Mg) and β-2-microglobulin. Additionally, the prevalence of hypertension and serum parathyroid hormone and aldosterone values were registered. Tubular function was compared with GFR and the risk of developing ESKD before November 2018. ResultsTwenty of the study patients (32%) had decreased GFR. In addition, 19% had proteinuria and 56% were hypertensive. Those without proteinuria or hypertension had better GFR values (P < .01 for both). There was a significant correlation between GFR and all the tubular function (P < .05) variables (except excretion of chloride) measured. Compared to the patients with favorable renal outcome, the patients (n = 10) who later developed ESKD had significantly (P < .01) lower GFR and reduced urinary excretion of all measured electrolytes except calcium. Consistently, urine β-2 microglobulin and serum parathyroid hormone and aldosterone values were significantly higher in the patients who developed ESKD (P ≤ .01). ConclusionBoth glomerular and tubular function decline was common and several parameters were likely to predict ESKD in posterior urethral valves patients.

Evaluation of Diuretic Activity and Phytochemical Contents of Aqueous Extract of the Shoot Apex of Podocarpus falcactus.

BackgroundIn Ethiopian folk medicine Podocarpus falcactus is used to treat stomachache, cancer, diabetes, and difficulty of urination. However, its diuretic activity has not been proven scientifically.ObjectiveTo determine the diuretic activity and phytochemical contents of the aqueous extract of the shoot apexes of Podocarpus falcactus.MethodsThe coarse powder of Podocarpus falcactus shoot apex was extracted by cold maceration using distilled water. Male rats were treated with distilled water, the standard drug (furosemide 10 mg/kg), and three different doses (100, 200, and 400 mg/kg) of the aqueous extract. The diuretic activity was determined by measuring parameters such as time to the first urination, volume, electrolyte concentration, and pH of urine. Electrolyte indices were calculated to elucidate the possible mechanism of diuresis. Additionally, qualitative and quantitative determination of phytochemicals in the plant extract was carried out.ResultsThe aqueous extract induced diuresis, natriuresis, and kaliuresis in a dose- and time-dependent manner as compared to the negative control. The extract at 200 and 400 mg/kg doses produced significant diuresis (p<0.001) by the end of the fifth hour compared to the negative control. Excretion of sodium, potassium, and chloride also significantly (p<0.001) increased following extract administration. In addition, there was a significant change in the pH of urine samples of the extract-treated group compared with the negative control. Qualitative and quantitative determination of phytochemicals revealed the presence of alkaloids, flavonoids, phenolics, and tannins with the value of 128.4 mg atropine equivalents (AE)/g, 142.23 mg quercetin equivalents (QE)/g, 196.84 mg gallic acid equivalents (GAE)/g, and 25.5 mg tannic acid equivalents (TAE)/g, respectively. The aqueous extract exhibited significant diuretic activity due to its phytochemical content, which could be used as a starting point for further studies.ConclusionThe aqueous extract showed significant diuretic activity and confirmed the folkloric use of Podocarpus falcactus.

Dietary Chloride Deficiency Syndrome: Pathophysiology, History, and Systematic Literature Review.

Metabolic alkalosis may develop as a consequence of urinary chloride (and sodium) wasting, excessive loss of salt in the sweat, or intestinal chloride wasting, among other causes. There is also a likely underrecognized association between poor salt intake and the mentioned electrolyte and acid–base abnormality. In patients with excessive loss of salt in the sweat or poor salt intake, the maintenance of metabolic alkalosis is crucially modulated by the chloride–bicarbonate exchanger pendrin located on the renal tubular membrane of type B intercalated cells. In the late 1970s, recommendations were made to decrease the salt content of foods as part of an effort to minimize the tendency towards systemic hypertension. Hence, the baby food industry decided to remove added salt from formula milk. Some weeks later, approximately 200 infants (fed exclusively with formula milks with a chloride content of only 2–4 mmol/L), were admitted with failure to thrive, constipation, food refusal, muscular weakness, and delayed psychomotor development. The laboratory work-up disclosed metabolic alkalosis, hypokalemia, hypochloremia, and a reduced urinary chloride excretion. In all cases, both the clinical and the laboratory features remitted in ≤7 days when the infants were fed on formula milk with a normal chloride content. Since 1982, 13 further publications reported additional cases of dietary chloride depletion. It is therefore concluded that the dietary intake of chloride, which was previously considered a “mendicant” ion, plays a crucial role in acid–base and salt balance.

Taxifolin improves disorders of glucose metabolism and water-salt metabolism in kidney via PI3K/AKT signaling pathway in metabolic syndrome rats

AimsOur study was designed to explore the function and mechanism of taxifolin on glucose metabolism and water-salt metabolism in kidney with metabolic syndrome (MS) rats. Main methodsSpontaneous hypertensive rats were induced by fructose to establish MS model. Systolic blood pressure (SBP) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured after 7 weeks of continuous administration with taxifolin. Kidney injury indices and histopathological evaluation were done. The apoptosis rate of primary kidney cells was detected by flow cytometry. Insulin signaling pathway related proteins and renal glucose transport-related proteins were detected by western blotting. We assessed the effects of taxifolin on sodium water retention and renin-angiotensin-aldosterone system (RAAS) in MS rats. We examined not only changes in urine volume, osmotic pressure, urinary sodium and urinary chloride excretion, but also the effects on NA+/K+-ATPase and RAAS indicators. We also detected changes in inflammatory factors by immunohistochemical staining and immunofluorescence. In vitro experiment, high glucose and salt stimulated NRK-52E cells. By adding the PI3K inhibitor (wortmannin) to inhibit the PI3K, the effects of inhibiting the PI3K/AKT signaling pathway on glucose metabolism, water-sodium retention and inflammatory response were discussed. Key findingsTaxifolin effectively reversed SBP, HOMA-IR, the kidney indices and abnormal histopathological changes induced by MS. Besides, taxifolin called back the protein associated with the downstream glucose metabolism pathway of PI3K/AKT. It also inhibited overactivation of RAAS and inflammatory response. In vitro experiments have demonstrated that the PI3K/AKT signaling pathway plays an important role in this process. SignificanceTaxifolin can improve homeostasis of glucose, inhibit overactivation of RAAS and reduce inflammatory response by PI3K/AKT signaling pathway.

Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease.

Current management of metabolic acidosis in patients with chronic kidney disease (CKD) relies on dietary intervention to reduce daily endogenous acid production or neutralization of retained acid with oral alkali (sodium bicarbonate, sodium citrate). Veverimer is being developed as a novel oral treatment for metabolic acidosis through removal of intestinal acid, resulting in an increase in serum bicarbonate. Veverimer is a free-amine polymer that combines high capacity and selectivity to bind and remove hydrochloric acid (HCl) from the gastrointestinal (GI) tract. In vitro studies demonstrated that veverimer had a binding capacity of 10.7 ± 0.4 mmol HCl per gram of polymer with significant binding capacity (>5 mmol/g) across the range of pH values found in the human GI tract (1.5-7). Upon protonation, veverimer bound chloride with high specificity but showed little or no binding of phosphate, citrate, or taurocholate (<1.5 mmol/g), which are all anions commonly found in the human GI tract. Administration of veverimer to rats with adenine-induced CKD and metabolic acidosis resulted in a significant increase in fecal chloride excretion and a dose-dependent increase in serum bicarbonate to within the normal range compared with untreated controls. Absorption, distribution, metabolism, and excretion studies in rats and dogs dosed with 14C-labeled veverimer showed that the polymer was not absorbed from the GI tract and was quantitatively eliminated in the feces. Acid removal by veverimer, an orally administered, nonabsorbed polymer, may provide a potential new treatment for metabolic acidosis in patients with CKD. SIGNIFICANCE STATEMENT: Metabolic acidosis is a complication of chronic kidney disease (CKD) as well as a cause of CKD progression. Veverimer is a high-capacity, selective, nonabsorbed, hydrochloric acid-binding polymer being developed as a treatment for metabolic acidosis. Veverimer binds and removes hydrochloric acid from the gastrointestinal tract, resulting in increased serum bicarbonate and the correction of metabolic acidosis. Veverimer is not an ion-exchange resin and does not deliver sodium or other counterions, and so it may be appropriate for patients with CKD with and without sodium-sensitive comorbidities.

Nephroprotective and antilithiatic activities of Costus spicatus (Jacq.) Sw.: Ethnopharmacological investigation of a species from the Dourados region, Mato Grosso do Sul State, Brazil

Ethnopharmacological relevanceCostus spicatus (Jacq.) Sw., also known as “cana-do-brejo,” is a species that is widely used in Brazilian traditional medicine for the treatment of kidney diseases. However, no studies have evaluated its nephroprotective and antilithiatic effects. AimTo investigate nephroprotective and antilithiatic effects of C. spicatus in a preclinical model of acute kidney injury (AKI) and in vitro nephrolithiasis. Materials and methodsC. spicatus leaves were collected directly from the natural environment in the Dourados region, Mato Grosso do Sul State, Brazil. The ethanol-soluble fraction of C. spicatus (ESCS) was obtained by infusion. Phytochemical characterization was performed by liquid chromatography coupled to diode array detector and mass spectrometer (LC-DAD-MS). We assessed whether ESCS has acute or prolonged diuretic activity. The nephroprotective effects of ESCS were evaluated in a model of AKI that was induced by glycerol (10 ml/kg, intramuscularly) in Wistar rats. Different doses of ESCS (30, 100, and 300 mg/kg) were administered orally for 5 days before the induction of AKI. Urinary parameters were measured on days 1, 3, 5, and 7. Twenty-four hours after the last urine collection, blood samples were obtained for the biochemical analysis. Blood pressure levels, renal vascular reactivity, renal tissue redox status, and histopathological changes were measured. Antilithiatic effects were evaluated by in vitro crystallization. Calcium oxalate precipitation was induced by sodium oxalate in urine samples with ESCS at 0.05, 0.5, and 5 mg/ml. ResultsFrom LC-DAD-MS analyses, flavonoids, saponins and other phenolic compounds were determined in the composition of ESCS. Significant reductions of the excretion of urinary total protein, creatinine, sodium, and potassium were observed in the AKI group, with significant histopathological damage (swelling, vacuolization, necrosis, and inflammatory infiltration) in the proximal convoluted tubule. Treatment with ESCS exerted a significant nephroprotective effect by increasing the urinary excretion of total protein, urea, creatinine, sodium, potassium, calcium, and chloride. All of the groups that were treated with ESCS exhibited a reduction of histopathological lesions and significant modulation of the tissue redox state. We also observed a concentration-dependent effect of ESCS on the crystallization of urinary crystals, with reductions of the size and proportion of monohydrated crystals. ConclusionThe data suggest that C. spicatus has nephroprotective and antilithiatic effects, suggesting possible effectiveness in its traditional use.

Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort.

Gitelman syndrome (GS) is a rare inherited salt-losing renal tubulopathy. Data on clinical features and the pregnancy outcome for female GS patients in a large cohort are lacking. The study was aimed to explore the phenotype and pregnant issue for female GS patients. GS cases from the National Rare Diseases Registry System of China (NRSC) were collected, and detailed clinical, laboratory and genetic data were analysed. Articles on pregnancy in GS were also systemically reviewed. A total of 101 GS patients were included; among them, 42.6% were female and 79.2% showed hypomagnesaemia. A lower proportion of female patients presented before 18 years of age, with less frequently reported polyuria, higher serum potassium and less urine sodium and chloride excretions. There was no gender difference in the sodium-chloride cotransporter (NCC) dysfunction evaluated by hydrochlorothiazide test. Twelve of the 43 female GS patients delivered after disease symptom onset, and their pregnancies were generally uneventful. As a group, pregnant GS patients had lower potassium levels in the first-trimester (P = .002) requiring higher potassium supplementation. After delivery, serum potassium (P = .02) and magnesium (P = .03) increased significantly. Both caesarean section and vaginal delivery were safe. Female GS patients may have a less severe phenotype with generally favourable outcomes of pregnancy. Intensive monitoring and increased potassium supplementation are necessary during pregnancy, especially in the first-trimester.

The Off-Target Effects, Electrolyte and Mineral Disorders of SGLT2i

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs that, in addition to emerging as an effective hypoglycemic treatment, have been shown to improve, in several trials, both renal and cardiovascular outcomes. In consideration of the renal site of action and the associated osmotic diuresis, a negative sodium balance has been postulated during SGLT2i administration. Although it is presumable that sodium and water depletion may contribute to some positive actions of SGLT2i, evidence is far from being conclusive and the real physiologic effects of SGLT2i on sodium remain largely unknown. Indeed, no study has yet investigated how SGLT2i change sodium balance in the long term and especially the pathways through which the natriuretic effect is expressed. Furthermore, recently, several experimental studies have identified different pathways, not directly linked to tubular sodium handling, which could contribute to the renal and cardiovascular benefits associated with SGLT2i. These compounds may also modulate urinary chloride, potassium, magnesium, phosphate, and calcium excretion. Some changes in electrolyte homeostasis are transient, whereas others may persist, suggesting that the administration of SGLT2i may affect mineral and electrolyte balances in exposed subjects. This paper will review the evidence of SGLT2i action on sodium transporters, their off-target effects and their potential role on kidney protection as well as their influence on electrolytes and mineral homeostasis.

586-P: Characteristics of 24-Hour Urinary Electrolyte Excretion and Its Correlation with Renal Function in Type 2 Diabetics

Objective: There are few studies on the characteristics of 24-hour urinary electrolyte excretion in patients with type 2 diabetes mellitus (T2DM),and it is unclear whether the level of 24-hour urinary electrolyte excretion is related to poor renal prognosis.This study aimed to explore associations between 24-hour urinary electrolyte excretion and renal function in T2DM patients. Methods: A total of 479 patients with T2DM in our hospital from 2018 to 2019 were enrolled. According to the estimated glomerular filtration rate (eGFR), patients were divided into normal group(eGFR≥90 mL/min/1.73m`2,n=317)and abnormal group(eGFR&amp;lt;90 mL/min/1.73m`2,n=162). The correlation between 24-hour urinary electrolyte excretion and eGFR in T2DM patients was analyzed. In addition, the 24-hour urine electrolyte excretion was compared with gender, diabetic duration, and HbA1c. Results: The levels of 24-hour urinary potassium, sodium and chlorine excretion in abnormal group were higher than normal group, the levels of calcium and phosphorus excretion were lower. Therein, levels of sodium(P=0.037) and calcium (P&amp;lt;0.001) had significant difference. The levels of 24-hour urinary potassium, sodium, chloride, calcium and phosphorus excretion in the male group were higher than female group, among which potassium (P&amp;lt;0.001), sodium (P=0.001), chloride (P=0.002), and phosphorus (P&amp;lt;0.001) were statistically significant. In addition, duration of disease and HbAlc was not related to 24-hour Urinary Electrolyte Excretion. Conclusion:There is a certain correlation between 24-hour urinary electrolyte excretion in T2DM and renal function. With the increase of 24-hour urinary sodium excretion and decrease of urinary calcium excretion, eGFR decreased, which was related to gender. Therefore, in patients with T2DM of the same gender, 24-hour urinary sodium and calcium excretion may be useful metabolic parameters for predicting poor renal prognosis, which needs further study. Disclosure Y. Wang: None. N. Li: None. L. Bu: None. H. Sun: None. B. Zhu: None. H. Li: None. S. Qu: None. Funding National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)

P0237COMPARISONS OF CLINICAL FEATURES IN GITELMAN SYNDROME PATIENTS WITH DIFFERENT URINARY CALCIUM EXCRETIONS

Abstract Background and Aims Hypocalciuria is considered typical in Gitelman syndrome (GS). However, a few GS cases diagnosed by gene testing presented as normocalciuria have been reported in recent years. Our study is to observe the clinical features in GS patients with different urinary calcium excretions, and investigate the value of urinary calcium excretion in the clinical classification for GS. Method GS cases from the National Rare Diseases Registry System of China (NRSC) (2016-2018) with SLCl2A3 gene screened in Peking Union Medical College Hospital were collected. The features of urinary calcium excretion were analyzed, and the phenotypes of patients with hypocalciuria were compared to those with normocalciuria. Hydrochlorothiazide (HCT) test was performed and the maximal increasement of chloride excretion fraction (△FECl) was calculated to evaluate the extent of NCC dysfunction. Results A total of 83 genetically proven GS patients was included, with the mean age at diagnosis of 31.0±13.0 years, and the male/female ratio was 1.4:1. Among them, 53 (63.9%) patients had hypocalciuria. The ratio of urinary calcium/creatine was significantly lower in patients with hypocalciuria (0.08±0.06mmol/mmol) compared to those with normocalciuria (0.47±0.28mmol/mmol), with a P value of &amp;lt;0.001. Age, gender, estimated glomerular filtration rate, blood pressure, alkalosis, and serum and urinary electrolytes including potassium, magnesium, natrium, chloride, and phosphorus were all comparable between patients with hypocalciuria and normocalciuria. Based on a standardized symptom questionnaire, fatigue (52.8% vs. 76.7%, P=0.03) and polyuria (9.4% vs. 30.0%, P=0.02) were less frequently reported in hypocalciuria patients, while all the other clinical symptoms were comparable. Sixteen patients in each group underwent HCT test, and the △FECl value was comparable between patients with hypocalciuria and normocalciuria (median, 0.54% vs. 0.83%, P=0.88), both of which indicated a blunt response to HCT (&amp;lt;2.86% according to our previous study). Conclusion The results show that 63.9% of the GS patients in this study had hypocalciuria. There is no definite relationship between urinary calcium excretion, phenotype and the extent of NCC dysfunction.

The impact of soil chloride concentration and salt type on the excretions of four recretohalophytes with different excretion mechanisms

Four natives Canadian recretohalophytic species: Atriplex canescens, Armeria maritima, Spartina pectinata, and Distichlis spicata were examined to determine their relative uptake and excretion of chloride in the context of phytoremediation. Adult plants were grown in soils contaminated with either sodium chloride or potassium chloride at various concentrations, then manually washed to collect the excreted salts. Atriplex canescens which has salt bladders, was found to have negligible excretions, suggesting that these structures release minimal amounts of salt onto the leaf’s surface. Chloride excretions of S. pectinata and D. spicata increased with higher soil chloride concentrations. A. maritima showed minimal excretion until a threshold soil salinity was reached. This species shifted from a reliance on internal sequestration to secretion at higher soil salinity. The salt used in the media did not impact these trends, but D. spicata excreted significantly more chloride under sodium chloride conditions. While all four species studied were able to translocate significant amount of salt to their shoots, only S. pectinata, D. spicata, and A. maritima are suitable candidates for remediation by haloconduction. Among these, A. maritima showed the greatest potential and significantly reduced the soil chloride concentration by up to 60% in the highest concentration treatment (4 mg/g).HIGHLIGHTSArmeria maritima, Spartina pectinata, and Distichlis spicata are suitable species for remediation via haloconduction.Armeria maritima had the highest total extraction capacity at high soil chloride.Spartina pectinata had the most consistent excretion capacity and is the most suitable for remediation of soils with lower soil chloride.

The tubular hypothesis of nephron filtration and diabetic kidney disease.

Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to the glomerulus: high levels of glucose in the glomerular filtrate drive increased reabsorption of glucose and sodium by the sodium-glucose cotransporters SGLT2 and SGLT1 in the proximal tubule. Passive reabsorption of chloride and water also increases. The overall capacity for proximal reabsorption is augmented by growth of the proximal tubule, which (alongside sodium-glucose cotransport) further limits urinary glucose loss. Hyperreabsorption of sodium and chloride induces tubuloglomerular feedback from the macula densa to increase GFR. In addition, sodium-glucose cotransport by SGLT1 on macula densa cells triggers the production of nitric oxide, which also contributes to glomerular hyperfiltration. Although hyperfiltration restores sodium and chloride excretion it imposes added physical stress on the filtration barrier and increases the oxygen demand to drive reabsorption. Tubular growth is associated with the development of a senescence-like molecular signature that sets the stage for inflammation and fibrosis. SGLT2 inhibitors attenuate the proximal reabsorption of sodium and glucose, normalize tubuloglomerular feedback signals and mitigate hyperfiltration. This tubule-centred model of diabetic kidney physiology predicts the salutary effect of SGLT2 inhibitors on hard renal outcomes, as shown in large-scale clinical trials.

Separating the effects of 24-hour urinary chloride and sodium excretion on blood pressure and risk of hypertension: Results from PREVEND.

ObjectiveResearch into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on blood pressure. This study aims to separate the specific effects of chloride and sodium intake on blood pressure.MethodsWe studied 5673 participants from the Prevention of Renal and Vascular End-Stage Disease(PREVEND) study. Urinary chloride(uCl) and sodium(uNa) were measured in two 24-hour collections. We used generalized-linear-regression to evaluate the relation of uCl and uNa with baseline blood pressure and Cox-proportional-hazards-analysis to assess the association with hypertension. Multicollinearity was assessed with Ridge regression.ResultsBaseline 24-hour uCl was 135±39mmol and uNa was 144±54mmol. The correlation between uCl and uNa was high (Pearson’s r = 0.96). UCl and uNa had similar non-significant positive and linear associations with blood pressure. In 3515 normotensive patients, 1021 patients developed hypertension during a median follow-up of 7.4 years. UCl and uNa had a comparable but non-significant J-shaped effect on the risk of hypertension. Adding both uCl and uNa to the same model produced instability, demonstrated by Ridge coefficients that converged or changed sign. The single index of uNa minus uCl showed a non-significant higher risk of hypertension of 2% per 10mmol/24-hour difference (HR1.02, 95%CI 0.98–1.06).ConclusionUCl and uNa had similar positive but non-significant associations with blood pressure and risk of hypertension and their effects could not be disentangled. Hence, the alleged adverse effects of high salt intake could be due to sodium, chloride or both. This encourages further study into the effect of chloride in order to complement dietary recommendations currently focused on sodium alone.

Regulatory safety pharmacology evaluation of BIA 10-2474

The present paper describes the regulatory safety pharmacology studies that were carried out to support the clinical trial application for BIA 10–2474. Animal studies complied with worldwide regulatory guidelines (e.g. EEC Council Directive 75/318/EEC and subsequent amendments). Oral administration of BIA 10–2474 at doses of 30, 100 and 300 mg/kg to male Han Wistar rats did not cause any significant physiological or behavioral changes, affect the respiration rate or the tidal volume, the gastrointestinal transit, urinary output volume or pH, nor urinary sodium, potassium or chloride excretion. BIA 10–2474, at 30 μg/mL, slightly, but significantly, reduced the hERG outward tail currents by 10.62%, but had no effect at 1, 3 or 10 μg/mL. BIA 10–2474 (1.5, 4.5 and 15 μg/mL) had no substantial effects on resting membrane potential (RMP), maximal upstroke velocity (Vmax), action potential amplitude (APA), action potential duration at 30%, 60% and 90% or action potential triangulation over the 30-min superfusion period in the dog isolated Purkinje fiber. In conscious dogs monitored by telemetry, BIA 10–2474 (20, 50 and 100 mg/kg p.o.) did not significantly modify arterial blood pressure as compared with controls (inter-group comparison), although a tendency toward an increase in arterial blood pressure was observed at 100 mg/kg, with systolic blood pressure being the most affected parameter. In conclusion, BIA 10–2474 had no adverse effects on any of the major vital organ systems, and, unfortunately, the data shed no further light on the mechanism(s) responsible for the clinical trial accident with BIA 10–2474.