Plasma Chloride Concentrations Research Articles

CaCl2-citrate regional anticoagulation with CVVHD leads to unwanted chloride loading compared to CVVH with systemic anticoagulation.

Chloride transfers during continuous renal replacement therapy (CRRT) have not been adequately described and may differ based on CRRT technique. We aimed to measure chloride mass transfer (JS,Cl) during CRRT and identify associated determinants. We performed a two-center, prospective, observational study in France and Australia in ICU patients with CRRT initiated for < 24h. Patients received continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD, with citrate-CaCl2 regional anticoagulation). Over a 24h period, plasma and effluent chloride concentrations were measured every 4h to compute chloride mass transfer (JS,Cl, in mmol.min-1) using a modality-specific model, with negative value indicating chloride transfer towards the patient. Secondary outcomes were the identification of CRRT settings associated with JS,Cl (using multivariate mixed effects regression). Results are presented with median [interquartile range]. Between February 2021 and August 2022, we enrolled 37 patients (64 [56-71] years, 67% male), for a total of 20 CVVHD and 20 CVVH sessions. Over 24h, plasma chloride concentrations were significantly higher, and JS,Cl significantly lower during CVVHD, compared to CVVH (-0.10 [-0.33-0.15] vs. 0.01 [-0.10-0.13] mmol.min-1, P<0.05). With both modalities, net ultrafiltration (QUFNET) and plasma chloride concentrations were the principal determinants of JS,Cl, with higher QUFNET being associated with an increase in JS,Cl during CVVHD. Also, CVVHD sessions demonstrated a concentration gradient between the plasma and the effluent chamber of -6 [-9- -4] mmol.L-1. Finally, CaCl2 reinjection during CVVHD accounted for 35% [32%-60%] of total JS,Cl in sessions with a negative JS,Cl. Compared to CVVH, CVVHD with regional citrate anticoagulation was associated with greater chloride mass transfer to the patient and higher plasma chloride concentrations. This was due to high dialysate chloride concentrations and CaCl2 reinjection. This effect could only be controlled by high net ultrafiltration flow rates.

Association between serum chloride levels and estimated glomerular filtration rate among US adults: evidence from NHANES 1999-2018.

Chloride, the predominant anion in extracellular fluid from humans, is essential to maintaining homeostasis. One important metric for thoroughly assessing kidney function is the estimated glomerular filtration rate (eGFR). However, the relationship between variations in serum chloride concentration and eGFR in general populations has been poorly studied. Therefore, the purpose of this study is to elucidate the correlation between serum chloride levels and eGFR within the United States' adult population. This cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES), which covered the years 1999-2018. We employed multiple linear regression analysis and subgroup analysis to evaluate the correlation between serum chloride concentration and eGFR. To examine the nonlinear association between serum chloride levels and eGFR, restricted cubic spline analyses were employed. Data from 49,008 participants in this cohort study were used for the chloride analysis. In the comprehensively adjusted model, a noteworthy inverse relationship was discovered between chloride plasma concentration and eGFR. Restricted cubic spline analyses revealed a significant nonlinear relationship between chloride levels and eGFR (P for overall < 0.001 and P for nonlinear < 0.001). A significant interaction was observed between eGFR and plasma chloride concentration (all P < 0.001 for interaction) among the subgroups characterized by sex, household income to poverty ratio, BMI, hypertension, and diabetes. Our findings suggest that higher levels of chloride plasma concentration were linked to decreased eGFR. These findings underscore the significance of monitoring chloride plasma concentration as a potential indicator for identifying individuals at risk of developing chronic kidney disease (CKD).

#2725 Chronic kidney disease is a risk factor for hyperchloremic metabolic acidosis after plasma exchange

Abstract Background and Aims Observational studies have demonstrated that metabolic acidosis due to hyperchloremia is an often encountered metabolic disorder following plasma exchange (PE) with an albumin-saline solution. Because of the reduced capacity for acid and chloride excretion, we hypothesized that patients with chronic kidney disease have the highest risk for hyperchloremic metabolic acidosis, in particular when multiple PE sessions are performed in a limited period. Method We prospectively collected data from all patients who received PE at Amsterdam UMC, between February 2023, and January 2024. We collected data on demographics, exchanged plasma volume, replacement fluids, and collected blood for analysis of sodium, chloride and bicarbonate before and after plasma exchange. We selected patients who received ≥5 plasma exchanges in an intensive cycle (≥4.2 sessions/week). We excluded patients who received Omniplasma, intravenous sodium bicarbonate or dialysis during the PE period. We assessed the effect of PE and kidney function on plasma bicarbonate and chloride concentration throughout the PE period with repeated measures mixed ANOVA, corrected for baseline plasma bicarbonate concentration, volume of exchanged plasma and PE intensity. Results Data from 26 patients, corresponding to 130 plasma exchanges, were included in the analysis. The mean age was 56 ± 14 years and 46% was female. Mean eGFR was 45 ± 14 ml/min/1.73 m2. Patients with an eGFR ≤59 ml/min/1.73 m2 (n = 17) had a significantly lower baseline plasma bicarbonate concentration (19.0 ± 2.8 versus 24.0 ± 1.9 mmol/L; p &amp;lt; 0.001) and used oral bicarbonate supplements (29% versus 0%; p = 0.02) more often than patients with an eGFR ≥60 ml/min/1.73 m2 (n = 9). Despite the lower baseline plasma bicarbonate and more frequent use of oral bicarbonate supplements, the plasma bicarbonate levels decreased the most in subjects with an eGFR ≤59 ml/min/1.73 m2 (mean difference −4.2; 95% CI −7.1 to −1.3; p = 0.006; Fig. 1A) during a cycle of 5 PE sessions. Baseline plasma chloride concentration was similar in both groups (103 ± 7 vs 103 ± 4 mmol/L) and increased the most in patients with an eGFR ≤59 ml/min/1.73 m2 (mean difference −1.4; 95% CI −2.2 to 5.0; p = 0.426; Fig. 1B). Conclusion Repeated plasma exchange with albumin-saline as a replacement fluid is associated with a significant decrease in plasma bicarbonate concentration in patients with impaired kidney function. Future studies should determine whether this hyperchloremic metabolic acidosis has impact on the patients’ symptoms or long-term outcome.

Diurnal rhythm of aquaporins expression and function in the kidney

Aquaporins (AQPs) are a protein family that plays a major role in maintaining water homeostasis. Aquaporin 2 (AQP2) and 3 (AQP3) are expressed on the collecting duct and regulated by the antidiuretic hormone, arginine vasopressin (AVP). AVP binds to its receptor on the collecting duct leading to increased expression of AQP2 on the apical membrane and AQP3 on the basolateral membrane to drive water reabsorption and promote urine concentration. We know that there are biological circadian rhythms that are critical for maintaining homeostasis. Therefore, we aimed to determine AQP2 and AQP3 expression and urine concentrating ability during their active time and inactive time in male and female mice. We hypothesize that there is a diurnal pattern in AQP2 and AQP3 expression or abundance leading to the variation of urine concentrating ability. Male (n=12) and female (n=12) C57BL/6J mice (10-11 weeks old) were euthanized in the middle of their active period (midnight) or the middle of their inactive period (noon). Spot urine osmolality was determined using a freezing point osmometer. Plasma sodium, chloride, and blood urea nitrogen (BUN) plasma concentration using an i-STAT blood analyzer. We localized aquaporins in kidney sections by using a diaminobenzidine chromagen method with antibodies against AQP2, AQP2 pS256 (an activation site), AQP2 pS261(an inhibitory site), and AQP3. Then, using a blinded method, the program Fiji Image J was used to quantify aquaporins on collecting ducts by using the integrated density (IntDen) parameter after calibrating into optical density (OD). We found that urine osmolality of control mice during their active period (2449±442.3 mOsm/ kg) was higher than that in the inactive time (1684±705.6 mOsm/kg, p = 0.0043). The plasma sodium concentration was higher in the active time (145±1.782 mmol/ L) than in the inactive time (142.9±1.311 mmol/L) with p = 0.0026. The plasma chloride (Cl−) and plasma BUN were also higher in the active time (Cl− = 115.2±1.4 mmol/L; BUN = 23±3.6 mmol/L) than in the inactive time mice (Cl− = 111±2.0 mmol/L, p &lt; 0.0001; BUN = 19.75±2.5 mmol/L, p = 0.0187). AQP2 was differentially expressed. During the active period, in both male and female mice, AQP2 was highly expressed in the collecting duct but was obviously reduced during the inactive period (active time = 4083±1006 OD; inactive time = 1243±608 OD, p &lt; 0.001). Moreover, AQP2 activation as determined by phosphorylation S256, was also greater during the active period (1148±404 OD) than inactive (221±96 OD, p = 0.002). Interestingly, the inhibitory site, phosphorylation of S261, was also greater during the active period (592 ± 378 OD) than the inactive period (162 ± 36 OD, p = 0.039). We found no significant difference in AQP3 localization or abundance. In summary, we showed that there is diurnal variability in urine osmolality (higher in their active period) that is supported by increased AQP2 expression during the active period of the mice, regardless of sex. Future studies will aim to determine if antagonizing and stimulating the vasopressin 2 receptor affects urine concentration in a diurnal manner. Intramural UAB funds to KAH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Predictive Value of Plasma Sodium and Other Laboratory Parameters in Determining Complicating Appendicitis in Children

Objective: Finding a reliable preoperative predictor of complicated acute appendicitis (AA) has been a challenging diagnostic problem. The present study aimed to identify potential factors that may predict complicated AA in the pediatric emergency department (ED) based on routine, widely available laboratory tests on admission to the ED, including plasma sodium concentration. Methods: We retrospectively reviewed clinical and laboratory data of pediatric patients with AA who underwent emergency surgery at our department between January 2020 and December 2022. The patients were divided into two groups: histopathologically proven complicated AA (n = 80) and noncomplicated AA (n = 155). Results: Complicated AA was associated with reduced plasma sodium and chloride concentrations (p p = 0.002), elevated C-reactive protein (CRP) (p p = 0.012 and 0.001, respectively). In binomial logistic regression, increased levels of CRP and WBC and decreased levels of sodium were predictors of complicated AA. The area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.764, 0.886). Conclusion: We identified mild hyponatremia and elevated CRP and WBC values as potential markers for distinguishing complicated from uncomplicated pediatric AA with implications for surgical approaches for treating complicated AA and conservative approaches for treating uncomplicated AA.

Short-term effects of small volume saline infusion on acid base equilibrium in critically ill patients.

Short-term acid-base effects of 0.9% saline solution infusion are not well described. Aim of this study was to assess the effects of a fluid challenge with 0.9% saline in critically ill patients according to the Stewart's approach, which allows a precise determination of acid base equilibrium. In 40 mechanically ventilated critically ill patients, acid-base variables according to Stewart's approach were measured before and after 30 minutes from the infusion of 0.5L of 0.9% saline. Patients were divided in saline responder (fractional sodium excretion increase <0.5) and non-responders, and in patients with (estimated glomerular filtration rate >63 mL/min) and without renal impairment. After saline infusion, plasma sodium concentration did not change (138 [135-141] vs. 138 [135-140] mEq/L, P=0.646), while chloride concentration significantly increased (102 [100-106] vs. 104 [191-106] mEq/L, P=0.003), reducing strong ion difference (37.0 [34.9-38.0] vs. 35.4 [32.7-37.5] mEq/L, P=0.004) without any impact on pH, due to the concomitant albumin dilution. In saline non-responders, the increase of plasma chloride concentration caused a reduction in strong ion difference, while in saline responders both plasma chloride concentration and strong ion difference remained similar. Patients with and without renal impairment presented a similar acid-base response. The infusion of 0.9% saline reduced strong ion difference by increasing plasma chloride concentration, with no effect on pH due to concomitant albumin dilution. Saline non-responders, characterized by the ability to excrete the sodium excess, were more likely to suffer the acidifying effects of saline infusion, while renal function did not affect the acid-base response to saline infusion.

Predictors of blood ionized calcium concentration in sick adult cattle.

Data on the factors affecting blood ionized calcium concentration (ciCa2+ ) and diagnostic performance of serum total calcium concentration (ctCa) measurements to detect abnormal blood iCa2+ status are lacking in sick adult cattle. Assess the association of ciCa2+ with venous blood pH, plasma concentrations of chloride (cCl), sodium (cNa), and potassium (cK), and ctCa, and total protein, albumin, and globulin concentrations in sick adult cattle. Two-hundred and sixty-five adult cattle (≥1-year-old) with different diseases. Prospective study. Whole blood pH, ciCa2+ , cNa, cK, and cCl were measured using a blood gas and electrolyte analyzer, whereas ctCa, and total protein, and albumin concentrations were determined using an autoanalyzer. The relationship between ciCa2+ and venous blood pH, plasma cCl, cNa, cK, and ctCa, and total protein, albumin, and globulin concentrations was investigated. Sensitivity and specificity were calculated for ctCa for diagnosis of abnormal ciCa2+ . Sensitivity of ctCa measurements to detect abnormal ciCa2+ was 66.0% whereas specificity of ctCa measurements was 72.3%. Serum total calcium concentration measurements accounted for 42% of adjusted blood ionized calcium (iCa2+ 7.40 ) concentration variance. Plasma cCl, and cK had explanatory power of ciCa2+ 7.40 , accounting for an additional 21% and 9% of the variance, respectively. Serum tCa measurements failed to accurately predict blood iCa2+ status in ill adult cattle. Serum tCa concentrations and plasma cCl were the strongest predictors of ciCa2+ in sick adult cattle.

ASSESSMENT OF RENAL FUNCTION IN DIABETIC WISTAR RATS TREATED WITH ETHANOL EXTRACT OF Cucumis sativus FRUIT.

As a fast-growing metabolic disorder diabetes mellitus is one of the leading causes of death worldwide. Nephropathy (damage to kidney leading to renal failure) is a microvascular complication of the disease. The aim of the present study was to assess renal function in diabetic rats treated with ethanol extract of Cucumis sativus fruit. Male Wistar rats (n = 25, mean weight = 215 ± 15 g) were randomly assigned to five groups (5 rats per group): control, diabetic, metformin, 200 mg/kg body weight (bwt) extract and 300 mg/kg bwt extract groups. Diabetes mellitus was induced in the rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg bwt. The diabetic rats were then treated for 21 days with metformin (50 mg/kg bwt) or the extract at doses of 200 and 300 mg/kg bwt, respectively, leaving the diabetic group untreated. The results showed that induction of diabetes mellitus using STZ significantly increased plasma urease activity, and urea and chloride concentrations, but it reduced the weight of rat kidney and concentrations of sodium, potassium and bicarbonate ions significantly (p &lt; 0.05). However, treatment of the diabetic rats with the extract markedly reduced plasma urease, and urea and chloride ion concentrations, while increasing kidney weight, organ/body weight ratio as well as concentrations of sodium, potassium and bicarbonate ions (p &lt; 0.05). The effect of the extract on potassium and chloride ions was dose-dependent. These results indicate that ethanol extract from the medicinal plant C. sativus fruit can ameliorate kidney dysfunction caused by STZ-induced diabetes mellitus.

The GH/IGF axis in the sea lamprey during metamorphosis and seawater acclimation

How the growth hormone (GH)/insulin-like growth factor (IGF) system affects osmoregulation in basal vertebrates remains unknown. We examined changes in the expression of components of the GH/IGF axis and gill ion transporters during metamorphosis and following seawater (SW) exposure of sea lamprey. During metamorphosis, increases in gill nka and nkcc1 and salinity tolerance were accompanied by increases in pituitary gh, liver igf1, gill ghr and igf1, but not liver ghr. SW exposure of fully metamorphosed sea lamprey resulted in slight increases in plasma chloride concentrations after SW exposure, indicating a high level of SW tolerance, but no major changes in mRNA levels of gill ion transporters or components of the GH/IGF axis. Our results indicate that metamorphosis is a critical point in the lifecycle of sea lamprey for stimulation of the GH/IGF axis and is temporally associated with and likely promotes metamorphosis and SW tolerance.

Altered Neuronal Discharge in the Organum Vasculosum of the Lamina Terminalis Contributes to Dahl Salt-Sensitive Hypertension.

Salt-sensitive hypertension in humans and experimental models is associated with higher plasma and cerebrospinal fluid sodium chloride (NaCl) concentrations. Changes in extracellular NaCl concentrations are sensed by specialized neurons in the organum vasculosum of the lamina terminalis (OVLT). Stimulation of OVLT neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP), whereas chronic activation produces hypertension. Therefore, the present study tested whether OVLT neuronal activity was elevated and contributed to SNA and ABP in salt-sensitive hypertension. Male Dahl salt-sensitive (Dahl S) and Dahl salt-resistant (Dahl R) rats were fed 0.1% or 4.0% NaCl diets for 3 to 4 weeks and used for single-unit recordings of OVLT neurons or simultaneous recording of multiple sympathetic nerves during pharmacological inhibition of the OVLT. Plasma and cerebrospinal fluid Na+ and Cl- concentrations were higher in Dahl S rats fed 4% versus 0.1% or Dahl R rats fed either diet. In vivo single-unit recordings revealed a significantly higher discharge of NaCl-responsive OVLT neurons in Dahl S rats fed 4% versus 0.1% or Dahl R rats. Interestingly, intracarotid infusion of hypertonic NaCl evoked greater increases in OVLT neuronal discharge of Dahl S versus Dahl R rats regardless of NaCl diet. The activity of non-NaCl-responsive OVLT neurons was not different across strain or diets. Finally, inhibition of OVLT neurons by local injection of the gamma-aminobutyric acid agonist muscimol produced a greater decrease in renal SNA, splanchnic SNA, and ABP of Dahl S rats fed 4% versus 0.1% or Dahl R rats. A high salt diet activates NaCl-responsive OVLT neurons to increase SNA and ABP in salt-sensitive hypertension.

Acid-base imbalances and the association of blood-gas variables, electrolytes, and biochemical analytes with outcome in hospitalized calves undergoing abdominal surgery.

Surgical abdominal emergencies in calves are associated with a guarded prognosis and have the potential for complex metabolic derangements including acid-base imbalances. To perform a comprehensive analysis of acid-base status and to assess the prognostic relevance of preoperative clinicopathologic variables in calves undergoing abdominal surgery. Hospital-based study samples of 535 (dataset 1; DS1) and 83 calves (dataset 2; DS2). Retrospective (DS1) and prospective (DS2) case series. In DS1, acidemia (pH <7.33) was present in 49.9%, whereas alkalemia (pH >7.37) was present in 30.7% of calves. Plasma L-lactate, chloride, and serum inorganic phosphorus concentration accounted for 51.9%, 11.6% and 9.4% of the variation of venous blood pH, respectively. Classification tree analysis indicated that a negative outcome (death or euthanasia during hospitalization) was associated with venous pO2 ≤33.6 mm Hg, anion gap >18.3 and >22.9mEq/L, serum albumin concentration ≤36.5 and ≤29.4g/L, serum urea concentration >4.4 mmol/L, and plasma ionized calcium concentration ≤1.26 mmol/L. The area under the receiver operating characteristic curve of this model was 0.85 (95% CI: 0.82-0.89, P < .001) and the resulting sensitivity and specificity for the prediction of nonsurvival at the optimal probability cut-point of 0.5 was 89.8% and 65.7%, respectively. In DS2 the model had a similar sensitivity and specificity of 90.5% and 70%, respectively. Clinicopathologic imbalances and associated changes of acid-base status are common in calves with surgical abdominal emergencies and have clinical utility for the prediction of a negative postoperative outcome.

Pathophysiological Electrolyte Changes Connoted via Antagonism of Serotonin Receptor in Experimental Animals

Background: Atypical antipsychotics are a subclass of antipsychotics that have emerged primarily since the 1970s for the treatment of psychiatric disorders. They are sometimes referred to as second-generation antipsychotics (SGAs). Several atypical antipsychotics have received regulatory approval for the treatment of disorders such as bipolar disorder, schizophrenia, irritability in autism, and as adjunctive treatment for major depressive disorders. Objectives: The purpose of the following study was to evaluate the effect of two widely known atypical antipsychotics, aripiprazole, and risperidone, on pathophysiological fluctuations in electrolytes. Several other studies were based on the following ideas, which brought a variety of different perspectives. As can be seen in the following evaluation, although atypical antipsychotics reduce the chance of extrapyramidal symptoms, it leads to impairment of renal function and destruction of renal histo-morphology. Materials and Methods: Thirty rats (10 per group) were used for this study, control group received normal saline, aripiprazole group received 10mg/kg//day, and risperidone group received 20mg/kg//day. The duration of therapy was long up to 3 months. Results: the results confirmed that both drugs reduced plasma sodium and chloride concentration with no effects on plasma potassium and calcium concentration. Moreover, the histomorphology at microscopic level shown no defects after 3 months of therapy. Conclusion: the outcome confirmed no deleterious defects associated with aripiprazole and risperidone when used for 3 months.

Phenotypic and genotypic characteristics of children with Bartter syndrome.

Bartter syndrome (BS) is a group of autosomal-recessive tubular disorders and it is classified into five genetic subtypes. BS can also be classified by phenotype (antenatal, classic). Patients with mutations in the same gene can present different phenotypes. In the present study, target gene sequencing was performed to evaluate the genotype-phenotype relationship. Biochemical, clinical and renal ultrasonography results were collected at presentation and the last clinic visit. Genetic analyses were performed. The findings of patients with classical BS (cBS) and antenatal BS (aBS) at presentation and the last visit were compared. Our study included 21 patients (12 female, 57.1%) from 20 families with BS. The median age at diagnosis was 8 months and the median follow-up period was 39 months. The most frequent complaint was growth failure. We have found 18 different types of mutations in four genes, including nine in the CLCNKB gene, seven in the SLCA12A1 gene, one in the KCNJ1 gene and one in the BSND gene. In ten patients, nine different types of CLCNKB gene mutations were detected, five of them were novel. Seven different mutations in the SLC12A1 gene were detected in eight patients, five of them were novel. Compared to patients with aBS and cBS, prematurity was significantly higher in the group with aBS. Nephrocalcinosis was present in only one patient with cBS, all the ten hypercalciuric patients with aBS had nephrocalcinosis at the time of diagnosis and the last visit. The mean height standard deviation score (SDS) of patients with aBS were significantly lower than the cBS group at the time of presentation. The mean weight SDS at the time of presentation was worse in patients with aBS than in patients with cBS. The mean plasma potassium and chloride concentrations were significantly lower in the patients with cBS at the time of diagnosis. This investigation revealed the mutation characteristics and phenotype-genotype relationship of our patients and provided valuable data for genetic counseling.

Changes in electrolyte concentrations and hydration status in endurance horses following transport and an overnight stay prior to competition.

To evaluate changes in electrolyte concentrations and hydration status that take place in endurance horses prior to the start of a competition and determine whether these changes would be associated with elimination. 19 horses entered in the 2016 Tevis Cup 100-Miles (160 km) One-Day Western States Trail Ride. Heparinized blood samples were collected at 5 time points: prior to transport to the ride (T0), during check-in the day before the ride (T1), 1 to 2 hours before the start of the ride (T2), at the 15-km mark (T3), and at the 55-km mark (T4). Packed cell volume and plasma sodium, potassium, chloride, urea nitrogen, glucose, bicarbonate, and total protein concentrations were determined and compared across time points and between finishers and nonfinishers. Signif icant differences were detected among plasma sodium, potassium, and urea nitrogen concentrations measured prior to the start of the ride (ie, T0, T1, and T2). For all variables except chloride and bicarbonate concentrations, significant differences were detected between values obtained prior to the start of the ride and values obtained during the ride (ie, T3 and T4). Only bicarbonate concentration at the 15-km mark of the ride was significantly associated with finishing status. Results suggested that significant changes in plasma sodium, potassium, and urea nitrogen concentrations can occur in endurance horses during transport to a competition and when horses are stabled overnight before an event. Additionally, a lower bicarbonate concentration following a steep climb early during the ride was associated with subsequent elimination.

Differential diagnosis of classical Bartter syndrome and Gitelman syndrome: Do we need genetic analysis?

Objective: Classical Bartter syndrome (cBS) and Gitelman syndrome (GS) are genotypically distinct, but there is a phenotypic overlapamong these two diseases, which can complicate the accurate diagnosis without genetic analysis. This study aimed to evaluate thecorrelation between clinical and genetic diagnoses among patients who have genetically defined cBS and GS.Patients and Methods: The study included 18 patients with homozygous/compound heterozygous CLCNKB (NM_000085) (n:10/18)and SLC12A3 (NM_000339) (n:8/18) mutations. Biochemical, clinical and radiological data were collected at presentation and at thelast visit.Results: In cBS group age at diagnosis, median plasma potassium and chloride concentrations were significantly lower and medianplasma HCO3 and blood pH values were significantly higher. Patients with GS had significantly lower median plasma magnesiumconcentrations and urinary calcium/creatinine ratio. One child with GS had normocalciuria, two children with cBS had hypocalciuriaand hypomagnesemia. Low estimated glomerular filtration rate (eGFR) (ml/dk/1.73m2) and growth failure were more evident in cBSgroup. In patients with cBS, nine different CLCNKB gene mutations were detected, five of them were novel. Novel mutations were:one nonsense (c.66G&amp;gt;A, p.Trp22*), one missense (c.499G&amp;gt;A, p.Gly167Ser) and three splice-site (c.867-2delA; c.499-2insG; c.1930-2A&amp;gt;C) mutations. In patients with GS, six different SLC12A3 gene mutations were found.Conclusions: It may not always be possible to clinically distinguish cBS from GS. We suggest to perform a genotypic classification ifgenetic analysis is possible.

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.

Tolerance and osmotic response to food deprivation and salt loading in the herbivorous non-drinking Moroccan Spiny-tailed lizard Uromastyx nigriventris (Sauria: Agamidae)

Abstract Animals inhabiting arid environments use a variety of behavioural and physiological strategies to balance their water and salt budgets. We studied the effects of dehydration and salt loading on osmoregulatory capacities in a large herbivorous desert lizard, the Moroccan Spiny-tailed lizard Uromastyx nigriventris, the family Agamidae. These lizards select plants with a high K+ to Na+ ratio of 15 to 20, and like other herbivorous lizards, effectively eliminate the extra electrolyte load, mainly via a pair of active nasal salt glands, which exude the extra ions from blood. Here we present results of a series of laboratory experiments, which tested a five-week food and water deprivation and the excretory response of nasal salt glands, during a short period of five days, following salt loading by two separated injections of KCl or NaCl at a 5-day interval (4th and 9th days). During food-water deprivation, hypohydrated lizards lost 32% of their initial body mass with a substantial decrease of their Body Condition Index and the tail volume as an index of energy (fat and then potential metabolic water) storage. Plasma osmolality significantly increased by 20%. There were also significantly increased plasma sodium, chloride, and total protein concentrations. On the other hand, there was no significant decrease in the plasma glucose level. Most of the salt loaded lizards secreted far more K+ than Na+ via the nasal glands, even after NaCl loading. The K+/Na+ ratio decreased only after two to three repetitive NaCl injections but insufficient Na+ was eliminated. Two successive KCl injections were successfully eliminated, but daily natural average K+ administration induced progressive hyperkaliemia. These experimental data agreed with previous observations showing variations of plasma Na+ and K+ concentrations in free-living lizards. The nasal gland constitutes the main route of Cl− excretion but the Cl−/(Na+ + K+) ratio may vary according to observations in other herbivorous species.

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial.

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration.Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment.Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy.Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

ELECTROLYTES CHANGES IN MALE RATS DEPRIVED OF FEED AND WATER

ABATRACT Electrolytes are of great importance in cell metabolism because they are important cofactors or coenzymes needed for normal functioning of cells. The disturbances of these electrolytes result in changes of cell pH and acid base balance. In order to determine the electrolytes changes following feed and water deprivation in male rats, a total of ten (n=10) male albino rats weighing (152 ± 3.50)g housed in metallic cage were used for this study. The rats were deprived of feed and water consecutively for six days. On the third and sixth days blood samples were obtained for electrolytes studies in the plasma and in the erythrocytes. There were significant increases (P<0.05) in plasma sodium, potassium, calcium, magnesium, chloride and bicarbonate concentrations in comparison to the basal parameters while significant decreases (P<0.05) in erythrocytes sodium, potassium, calcium, magnesium, chloride and bicarbonate concentrations in comparison to the basal parameters were observed. It can be concluded that deprivation of male albino rats of food and water for six consecutive days resulted in perturbation, stress, dehydration and redistribution of electrolytes in various compartments of the cell

Rapid recovery of normal gill morphology and blood physiology in brown trout (&lt;em&gt;Salmo trutta&lt;/em&gt;) after short-term exposure to toxic concentrations of aqueous aluminium under non-steady state chemical conditions

Freshwater acidification is characterised by elevated concentrations of aqueous aluminium. Global emissions of acidifying agents are reduced due to international agreements, and freshwater acidification has shifted from chronic to a more episodic character. The recovery of fish populations in acidified areas is likely to depend on the individual’s ability to recover from short-time aluminium exposures. We exposed brown trout (Salmo trutta) to an Al-rich medium, nominal concentration 600 µg L–1, for 0.5, 2, 6, 8 and 11 hours, before transfer to circumneutral Al-poor water for recovery. As controls, fish were either exposed for 11 hours to an acidified Al-poor medium or to untreated water. Some mortality during the first 24 hours of the recovery period occurred in fish exposed for 11, 8 and 6 hours to aluminium. No mortality during recovery was observed in the remaining groups. Aluminium exposure led to increased haematocrit and plasma lactate concentration, decreased plasma chloride concentration, deposition of aluminium on gill surfaces, and morphological alteration of the gill structures. The responses depended on exposure time. Aluminium deposited on the gill disappeared and plasma lactate levels were at control levels after 1 day in the recovery water, while haematocrit and plasma chloride levels were at control levels after 14 days of recovery. Gills in fish exposed to aluminium for 11 hours were almost fully recovered after 14 days. We conclude that the toxic response in brown trout exposed to an acutely toxic aluminium challenge is reversible. Moreover, the first 24 hours after aluminium exposures is the most critical period for the fish recovery. Further, it takes no more than 14 days for brown trout to fully recover from an acute toxic aluminium exposure, and only 1 day if the aluminium challenge is moderate.