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Background: Chloride plays a crucial role in renal salt sensing. This study investigates whether serum chloride is associated with clinical outcomes and decongestive response to acetazolamide in patients with acute decompensated heart failure., Methods: This post hoc analysis includes all 519 patients from the ADVOR trial (Acetazolamide in Decompensated Heart Failure With Volume Overload), randomized to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The impact of baseline serum chloride on the main trial end points and the treatment effect of acetazolamide was assessed, as was the evolution of serum chloride under decongestive treatment., Results: Hypochloremia (<96 mmol/L) and hyperchloremia (>106 mmol/L) were present in 80 (15%) and 53 (10%), respectively, at baseline. Hypochloremia was associated with significantly slower decongestion, a longer length of hospital stay, and increased risk of all-cause mortality and heart failure readmissions. Acetazolamide increased the odds of successful decongestion and reduced length of stay irrespectively of baseline serum chloride levels. No statistically significant interaction between serum chloride levels and the effect of acetazolamide on death or heart failure readmissions was observed. The placebo group exhibited a progressive decline in serum chloride, which was effectively prevented by acetazolamide ( P <0.001)., Conclusions: Hypochloremia is associated with diuretic resistance and worse clinical outcomes. Add-on acetazolamide therapy improves decongestion across the entire range of serum chloride and prevents the drop in chloride levels caused by loop diuretic monotherapy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03505788., Competing Interests: Dr Damman reports speaker/consultancy and research fees to his institution from Astra Zeneca, Abbott, Novartis, FIRE1, and Boehringer Ingelheim. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the past 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research, educational, and travel grants from Abbott, Amgen, Astra Zeneca, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and Zoll Medical UK. The research and educational grants do not impact on Dr Ruschitzka’s personal remuneration. Dr Verbrugge reports a consulting relationship with Abbott Laboratories, Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb Belgium, Daiichi-Sankyo, Menarini Benelux, MSD, Novartis Pharma, Novo Nordisk Pharma, Pfizer, Roche Diagnostics, and Qompium.

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Prerenal acute kidney injury (AKI) is associated with profound hypovolemia and reduced renal perfusion. Results regarding hyperchloremia-associated AKI in patients with DKA are conflicting; we therefore investigated the potential relationship between hyperchloremia status and the risk of developing AKI. This single-center cohort study included 113 newly diagnosed T1DM patients with DKA admitted to the pediatric intensive care unit. Laboratory parameters, including Na, K, urea, creatinine, and chloride levels, were retrospectively reviewed at the time of presentation and at 12, 24 and 36 h. AKI was defined using the eGFR according to the pediatric RIFLE classification criteria. Twenty-two (19.5%) of the 113 patients were in the AKI group. Two-way repeated-measures ANOVA showed significant (P values ≤ 0.01) time interaction effects within the groups based on the eGFR and the serum chloride, hyperchloremia, and phosphate levels. Serum chloride levels did not differ between the groups during the first 12 h (p > 0.05) but were significantly greater in the AKI group than in the non-AKI group at 24 h and 36 h (p < 0.01). The final DKA resolution time was significantly greater in the AKI group than in the non-AKI group [22.2 (9.5) vs. 17.0 (12.0) h, respectively; p = 0.03]. However, the groups had similar lengths of hospital stay [13.0 (8.0) days vs. 12.0 (4.0) days, respectively; p = 0.17].Conclusions: Hyperchloremia may be iatrogenic rather than causative during treatment. This may worsen renal failure and prolong the recovery and treatment time for DKA patients. What is Known? • Acute kidney injury resulting from severe volume depletion is a common occurrence in diabetic ketoacidosis and typically requires significant volume replacement therapy. • In recent years, hyperchloremia has been associated with increased risks of AKI, morbidity, and mortality in some conditions, such as diabetic ketoacidosis. What is New? • The incidence of hyperchloremia increases over time during the treatment of diabetic ketoacidosis. • Hyperchloremia may be an iatrogenic element rather than a cause of acute kidney injury during the treatment of diabetic ketoacidosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In patients with heart failure (HF), multiple electrolyte disorders are common, and recent studies have shown that chloride disorders play a significant role in the prognosis of HF. Data about the prevalence and prognostic role of hypochloremia in patients with acute HF (AHF) are scarce in African nations, including Ethiopia. Hence, this study aimed to assess the prevalence, associated factors, and prognostic role of hypochloremia in patients with AHF in Ethiopia., Methods: This was a single-center retrospective analysis of AHF patients, aged ≥15 years, with chloride determination upon admission to the medical wards and medical ICU of Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia, from July 1, 2022, to July 1, 2023. Statistical Package for Social Sciences, version 26, was used to enter and analyze the data. Descriptive analysis was used to summarize clinical profiles, laboratory data, and outcomes of AHF patients stratified by the presence and absence of hypochloremia. Logistic regression analysis was used to determine the factors associated with hypochloremia and to assess the association of hypochloremia and other factors with in-hospital mortality in patients with AHF. A two-tailed P value <0.05 was regarded as statistically significant., Results: A total of 267 AHF patients who had chloride determination on admission were included in this study; the mean age was 56.7 years (standard deviation: 18.6), and the gender-based distribution of the patients was nearly equal. The prevalence of hypochloremia was 36.7%. Diastolic blood pressure <60 mm Hg [adjusted odds ratio (AOR) = 3.63, 95% confidence interval (CI), 1.04, 12.72] and hyponatremia (AOR = 29.20, 95% CI, 13.21, 64.56) were significantly associated with hypochloremia. The in-hospital mortality rate was higher in AHF patients with hypochloremia (16.3%) compared to those without hypochloremia (4.7%). The odds of in-hospital mortality among AHF patients with hypochloremia were 2.8 times higher compared to patients without hypochloremia (AOR = 2.82, 95% CI: 1.08, 7.04) after adjusting for ICU admission, systolic blood pressure < 120 mm Hg and diastolic blood pressure < 60 mm Hg., Conclusions: This study revealed a high prevalence of hypochloremia among patients with AHF. Low diastolic blood pressure and hyponatremia were significantly associated with the development of hypochloremia. Most importantly, AHF patients with hypochloremia had a higher in-hospital mortality rate compared to those without hypochloremia. Hence, hypochloremia on admission should be considered a potential prognostic factor in patients with AHF, and further research with a larger sample size is needed to support the findings of this study., Competing Interests: The author have declared that no competing interests exist., (Copyright: © 2024 Gashaw Solela. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: As exacerbations of chronic obstructive pulmonary disease (COPD) are one of the leading causes of hospitalization and are associated with significant mortality, it is particularly important to accurately assess the risk of exacerbations in COPD. Most of the current clinical biomarkers are related to inflammation and few consider how ion levels affect COPD. Chloride ion, the second most abundant serum electrolyte, has been shown to be associated with poor prognoses in several diseases, but their relationship with COPD remains unclear., Methods: In total, 105 patients with acute exacerbations of COPD were recruited. Data on clinical characteristics, lung function, blood count, blood biochemistry, relevant scales including the Clinical COPD Questionnaire (CCQ), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index and the St. George's Respiratory Questionnaire (SGRQ) were collected from all patients for statistical analysis., Result: There were significant differences in lung function indicators and disease severity in the low chloride ion subgroup compared with the high chloride ion subgroup. On multiple logistic regression analysis, chloride ion was an independent factor affecting lung function in COPD patients (OR=0.808, 95% CI: 0.708 - 0.922, p=0.002). The sensitivity of chloride ion in predicting COPD severity was 78%, the specificity was 63%, and the area under the curve was 0.734 (p<0.001). Subgroup analysis showed that chloride ion was a stronger predictor in male and smoking patients., Conclusions: Chloride ion was a novel prognostic biomarker for COPD, and low levels of chloride ion were independently associated with exacerbations in COPD patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus Disease-2019 (COVID-19) has posed formidable challenges to healthcare systems. Exploring novel biomarkers that can provide valuable prognostic insights, particularly in critically ill patients, has a significant importance. Against this backdrop, our study aims to elucidate the associations between serum chloride levels and clinical outcomes. Methods: A total of 499 patients were enrolled into the study. The serum chloride levels of patients upon hospital admission were recorded and then categorized into three groups (hypochloremia, normochloremia, and hyperchloremia) for the evaluation of clinical outcomes. Additionally, serum C-reactive protein, procalcitonin, and D-dimer measurements were recorded for further evaluation. Results: A total of 390 (78.1%) patients tested positive for COVID-19 via polymerase chain reaction testing. Non-contrast thorax computed tomography scans were indicative of COVID-19 compatibility for all patients. A total of 210 (42%) patients were female and 289 (58%) were male. A total of 214 (42.8%) patients necessitated tocilizumab intervention; 250 (50.1%) were at an intensive care unit (ICU), with 166 (66.4%) of them receiving tocilizumab. A total of 65 (13%) patients died, 40 (61.5%) of whom received tocilizumab; 41 (63%) were in the ICU. Serum chloride levels upon admission were markedly lower and elevated D-dimer levels were apparent in tocilizumab users, patients requiring ICU care, and patients who died. Conclusions: our findings provide robust evidence supporting the value of serum chloride levels as a prognostic biomarker in critically ill COVID-19 patients.

Purpose: The purpose of this therapeutic update is to provide pharmacists with a general overview of the pathophysiology of hyperchloremia and describe strategies to help prevent development of this electrolyte abnormality in hospitalized patients., Summary: Hyperchloremia is an electrolyte abnormality associated with an increased incidence of acute kidney injury and metabolic acidosis. Intravenous (IV) fluids utilized for volume resuscitation, medication diluents, and total parental nutrition all may contribute to the development of hyperchloremia. Current evidence suggests that administration of balanced crystalloids for either fluid resuscitation or maintenance fluids may impact serum chloride levels and patient outcomes. In multiple randomized controlled trials, administering balanced crystalloids for fluid resuscitation in critically ill patient populations did not decrease mortality. However, further analyses of subpopulations within these trials have demonstrated that patients with sepsis may benefit from receiving balanced crystalloids for initial fluid resuscitation. Results from several small studies suggest that altering the composition of these IV fluids may help prevent development of hyperchloremia., Conclusion: Management of hyperchloremia is preventative in nature and can be mitigated through management of resuscitation fluids, medication diluents, and total parenteral nutrition. Inpatient pharmacists should be aware of the potential risk of fluid-associated hyperchloremia and assist with optimal fluid management to prevent and manage hyperchloremia., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS)., Methods: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient., Results: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants., Conclusions: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Chloride has prognostic implications in heart failure (HF). The sodium:chloride (Na:Cl) ratio gathers information of both ions., Objectives: To study the prognostic impact of Na:Cl ratio in acute HF., Methods: We retrospectively analysed patients included in an acute HF cohort in 2009-2010., Primary Endpoint: all-cause mortality., Follow-Up: 1-year from admission to study the impact of admission Na:Cl ratio; 1-year post-discharge to study the discharge ratio impact. ROC curves of the association of Na, Cl, and the Na:Cl ratio with 1-year mortality were determined and the AUC compared. The association of Na:Cl ratio with mortality was assessed in multivariate analyses., Results: We studied 616 patients. Median admission Na:Cl ratio = 1.34 (1.31-1.38). During 1-year since admission, 229 patients died, AUC for death-association of admission Na, Cl and Na:Cl ratio = 0.42 (0.38-0.47), 0.39 (0.35-0.44) and 0.58 (0.53-0.63), respectively, with significant difference between Na:Cl ratio curve and the others. When admission Na:Cl ratio ≥ 1.34, the multivariate-adjusted death-risk was 1.41 (1.04-1.89); 1.32 (1.04-1.68), per each 0.1 increase in ratio. In-hospital death rate was 4.1 %, median discharge Na:Cl ratio = 1.40 (1.37-1.45). During 1-year post-discharge, 205 patients (34.9 %) died; AUC for Na, Cl and Na:Cl ratio: 0.45 (0.40-0.50), 0.41 (0.36-0.46) and 0.57 (0.52-0.62), with differences between Na:Cl ratio curve and the others. When discharge Na:Cl ratio ≥ 1.43 (percentile 66.7), the adjusted-HR of death was 1.43 (1.04-1.97), p = 0.03, 1.54 (1.23-1.92) per 0.1 increase., Conclusions: Elevated Na:Cl ratio is independently associated with all-cause death. Per each 0.1 increase in Na:Cl ratio at admission and discharged, there was a 32 % and 54 % higher risk, respectively., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: 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., Methods: 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., Results: 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., Conclusion: 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)., (© 2024. The Author(s).)

This study aimed to investigate the association between serum chloride levels and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were extracted for analysis. Demographic information, laboratory results, medical histories, vital signs, and prognosis-related data were collected. Cox proportional hazard models were used to assess the relationship between serum chloride levels and 90-day and 365-day mortality. Subgroup analyses were conducted to explore potential interactions between serum chloride levels and various factors. The study included patients with a median age of 72.00 years, of whom 52.39% were male. Higher quartiles of serum chloride levels were associated with significantly lower levels of weight, RBC, platelet, hemoglobin, and other variables (P < 0.05), accompanied by lower 90-day and 365-day mortality (P < 0.05). Cox proportional hazard model indicated that the risk of death was significantly lower in the fourth quartile of serum chloride levels compared with the first quartile after adjusting for confounders (90-day HR = 0.54, 365-day HR = 0.52, both P < 0.05). An L-shape relationship was observed, with risks of death decreasing as serum chloride levels increased, although the magnitude decreased when levels reached 102 mmol/L. This study demonstrated an independent L-shaped association between serum chloride levels and all-cause mortality in critically ill patients with COPD. This finding helps us to understand the prognostic value of serum chloride levels in critically ill patients with COPD., (© 2024. The Author(s).)

The present study investigated the prevalence of blood chloride (Cl) abnormalities in diarrheic neonatal calves with metabolic acidosis and attempted to identify the most relevant electrolyte abnormality to these abnormalities. A retrospective analysis was conducted on the medical records of 157 diarrheic neonatal calves aged 10.3 ± 4.2 days old with metabolic acidosis. Hypochloremia, normochloremia, and hyperchloremia were observed in 8.9% (14/157), 43.3% (68/157), and 47.8% (68/157), respectively, of diarrheic calves with metabolic acidosis. This distribution remained similar regardless of age (under 8 days or 8 days and older). Furthermore, a multiple logistic regression analysis showed that variations in values for blood sodium [Na (regression coefficients 0.877; 95% confidence interval (CI) 13.977-134.195; P<0.01)], pH (regression coefficients -10.719; 95% CI -19.076- -2.362; P<0.05), and bicarbonate [HCO 3 - (regression coefficients -0.555; 95% CI -0.820- -0.290; P<0.01)] were associated with blood Cl abnormalities. The present results revealed that blood Na concentrations were more strongly associated with blood Cl concentrations than blood pH and HCO 3 - values. In the present study, diarrheic calves with hyperchloremia were characterized by normonatremia and extremely severe metabolic acidosis.

Aims: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure., Methods: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed., Results: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses., Conclusion: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The prognostic nutritional index (PNI) and serum chloride level are related to adverse outcomes in patients with heart failure. However, little is known about the relationship between the PNI and serum chloride level in predicting the poor prognosis of patients with acute decompensated heart failure (ADHF)., Methods and Results: We reviewed 1221 consecutive patients with ADHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in hospital death, missing follow-up data, missing chloride data, missing lymphocyte (LYM) count data, or missing serum albumin data, 805 patients were included. PNI was calculated using the formula: serum albumin (ALB) (g/L) + 5 × LYM count (10^9/L). Patients were divided into 4 groups according to the quartiles of the PNI, and the highest PNI quartile (PNI Q4: PNI ≥ 47.3) was set as the reference group. The patients in the lowest PNI quartile (PNI Q1: PNI < 40.8) had the lowest cumulative survival rate, and mortality risk decreased progressively through the quartiles (log-rank χ 2 142.283, P < 0.0001). Patients with ADHF were divided into 8 groups by quartiles of PNI and median levels of serum chloride. After adjustment, the hazard ratio (HR) for all-cause mortality in ADHF patients in Group 1 was 8.7 times higher than that in the reference Group 8. Furthermore, the addition of serum chloride level and PNI quartile to the Cox model increased the area under the Receiver operating characteristic (ROC) curve by 0.05, and the area under the ROC curve of the new model was higher than that of the original model with traditional risk factors., Conclusions: Both the lowest PNI quartiles and low chloride level indicate a higher risk of all-cause death in patients with ADHF., (© 2024. The Author(s).)

Background: Timely diagnosis and prevention of diseases require rapid and sensitive detection of biomarkers from blood samples without external interference. Abnormal electrolyte ion levels in the blood are closely linked to various physiological disorders, including hypertension. Therefore, accurate, interference-free, and precise measurement of electrolyte ion concentrations in the blood is particularly important., Results: In this work, a colorimetric sensor based on a biphasic microdroplet extraction is proposed for the detection of electrolyte ions in the blood. This sensor employs mini-pillar arrays to facilitate contact between adjacent blood microdroplets and organic microdroplets serving as sensing phases, with any color changes being monitored through a smartphone's colorimetric software. The sensor is highly resistant to interference and does not require pre-treatment of the blood samples. Remarkably, the sensor exhibits exceptional reliability and stability, allowing for rapid enrichment and detection of K + , Na + , and Cl - in the blood within 10 s (Cl - ), 15 s (K + ) and 40 s (Na + ) respectively., Significance: The colorimetric sensor based on biphasic microdroplet extraction offers portability due to its compact size and ease of operation without the need for large instruments. Additionally, it is location-independent, making it a promising tool for real-time biomarker detection in body fluids such as blood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: This study aimed to examine whether the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) reference intervals for 19 commonly used biochemical assays (potassium, sodium, chloride, calcium, magnesium, inorganic phosphorous, glucose, urea, creatinine, direct and total bilirubin, C-reactive protein (CRP), total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD)) could be applied to the newborn population of one Croatian clinical hospital., Materials and Methods: Reference interval verification was performed according to the CLSI EP28-A3c guidelines. Samples of healthy newborns were selected using the direct a posteriori sampling method and analyzed on the Beckman Coulter AU680 biochemical analyzer. If verification wasn't satisfactory, further procedure included de novo determination of own reference intervals by analyzing 120 samples of healthy newborns., Results: After the first set of measurements, 14/19 tested reference intervals were adopted for use: calcium, inorganic phosphorous, glucose, urea, creatinine, total bilirubin, CRP, total protein, albumin, AST, ALT, GGT, ALP and LD. A second set of samples was tested for 5 analytes: potassium, sodium, chloride, magnesium and direct bilirubin. The verification results of the additional samples for sodium and chloride were satisfactory, while the results for potassium, magnesium and direct bilirubin remained unsatisfactory and new reference intervals were determined., Conclusions: The CALIPER reference intervals can be implemented into routine laboratory and clinical practice for the tested newborn population for most of the analyzed assays, while own reference intervals for potassium, magnesium and direct bilirubin have been determined., Competing Interests: Potential conflict of interest None declared., (Copyright Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Hyperglycemic emergencies frequently lead to acute kidney injury (AKI) and require treatment with large amount of intravenous fluids. However, the effects of chloride loading on this population have not yet been investigated. We conducted a multicenter, retrospective, cohort study in 21 acute-care hospitals in Japan. The study included hospitalized adult patients with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) who had AKI upon arrival. The patients were classified into high and low chloride groups based on the amount of chloride administered within the first 48 h of their arrival. The primary outcome was recovery from AKI; secondary outcome was major adverse kidney events within 30 days (MAKE30), including mortality and prolonged renal failure. A total of 390 patients with AKI, including 268 (69%) with DKA and 122 (31%) with HHS, were included in the study. Using the criteria of Kidney Disease Improving Global Outcomes, the severity of AKI in the patients was Stage 1 (n = 159, 41%), Stage 2 (n = 121, 31%), and Stage 3 (n = 110, 28%). The analysis showed no significant difference between the two groups in recovery from AKI (adjusted hazard ratio, 0.96; 95% CI 0.72-1.28; P = 0.78) and in MAKE30 (adjusted odds ratio, 0.91; 95% CI 0.45-1.76; P = 0.80). Chloride loading with fluid administration had no significant impact on recovery from AKI in patients with hyperglycemic emergencies.Trial Registration This study was registered in the UMIN clinical trial registration system (UMIN000025393, registered December 23, 2016)., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Objective: To compare the short-term effects on acid base, electrolyte status and urine output of a single fluid bolus of saline to that of the balanced solution Plasmalyte ® in critically ill patients., Methods: Prospective, randomized, controlled trial. Adult patients (≥ 18 years) admitted to the ICU receiving a fluid bolus were randomized to receive 1 L of saline (NaCl 0.9%, Baxter) or a balanced fluid [Plasmalyte ® (Baxter)]. Blood samples and urine output were collected just before (T0), just after (T1), 2 h after (T2) (only for urinary output) and three hours after termination of the fluid bolus (T4). The effect of fluid boluses on serum chloride, apparent strong ion difference, base excess, urinary output and blood pressure or vasopressor need were analyzed., Main Results: Patients who received a 1 L saline fluid bolus had a significant increase in serum chloride (1.60; 95% CI 1.10 to 2.10; P < 0.001) and short-term decrease in apparent strong ion difference (- 1.85; 95% CI - 2.71 to - 0.99; P < 0.001) and base excess (- 0.90; 95% CI - 1.31 to - 0.50; P < 0.001). We observed a 17% increase in patients developing hyperchloremia in the saline group (0.17; 95% CI 0.05 to 0.29; P = 0.005). No significant difference in urinary output, blood pressure or vasopressor need was observed in either group., Conclusion: Even a single, small bolus of saline, administered to critically ill patients, causes a significant increase in chloride concentration and a decrease in apparent strong ion difference and base excess, and an increase in the number of patients developing hyperchloremia. No difference in effect on urinary output, blood pressure or vasopressor need was observed between the two groups., Eudract Number: 2014-001005-41; date of registration: 28/10/2014., Local Ec Approval: EC project number 2014/038., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Patients with primary aldosteronism have an increased risk of developing cardiovascular disease. The response to mineralocorticoid receptor antagonists varies among individuals, indicating diverse mineralocorticoid receptor activities in these patients. This study explored the factors linked to the efficacy of blood pressure reduction through mineralocorticoid receptor antagonists in patients with primary aldosteronism. We examined the relationship between the reduction in blood pressure and patient characteristics in a group of 41 patients with primary aldosteronism (24 males, mean age 55 ± 13 years, including 34 patients diagnosed with bilateral primary aldosteronism) before and after undergoing treatment with mineralocorticoid receptor antagonists. Significant reductions in office blood pressure were observed 3 and 6 months after treatment initiation. Single correlation analyses showed that the urinary chloride-to-potassium ratio displayed the strongest positive association with blood pressure reduction, surpassing plasma aldosterone concentration, plasma renin activity, and urinary sodium-to-potassium ratio, at 3 and 6 months. Multiple correlation analyses revealed a consistent and independent positive correlation between the urinary chloride-to-potassium ratio and blood pressure reduction at 3 and 6 months. The optimal threshold for the urinary chloride-to-potassium ratio with respect to its ability to lower blood pressure, was determined as 3.18. These results imply that the urinary chloride-to-potassium ratio may be independently associated with the effectiveness of blood pressure reduction facilitated by mineralocorticoid receptor antagonists. Moreover, it could potentially serve as a valuable predictor of the effectiveness of these agents and function as an indicator of endogenous mineralocorticoid receptor activity in patients with primary aldosteronism., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Importance: Deaths due to neonatal calf diarrhea are still one of the most critical problems of cattle breeding worldwide. Determining the parameters that can predict diarrhea-related deaths in calves is especially important in terms of prognosis and treatment strategies for the disease., Objective: The primary purpose of this study was to determine mortality rates and durations, survival status, and predictive prognosis parameters based on vital signs, hematology, and blood gas analyses in neonatal diarrheic calves., Methods: The hospital automation system retrospectively obtained data from 89 neonatal diarrheic calves., Results: It was found that 42.7% (38/89) of the calves brought with the complaint of diarrhea died during hospitalization or after discharge. Short-term and long-term fatalities were a median of 9.25 hours and a median of 51.50 hours, respectively. When the data obtained from this study is evaluated, body temperature (°C), pH, base excess (mmol/L), and sodium bicarbonate (mmol/L) parameters were found to be lower, and hemoglobin (g/dL), hematocrit (%), lactate (mmol/L), chloride (mmol/L), sodium (mmol/L) and anion gap (mmol/L) parameters were found to be higher in dead calves compared to survivors. Accordingly, hypothermia, metabolic acidosis, and dehydration findings were seen as clinical conditions that should be considered. Logistic regression analysis showed that lactate (odds ratio, 1.429) and CI - (odds ratio, 1.232) concentration were significant risk factors associated with death in calves with diarrhea., Conclusions and Relevance: According to the findings obtained from this study, the determination of lactate and Cl - levels can be used as an adjunctive supplementary test in distinguishing calves with diarrhea with a good prognosis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background: some studies suggest that hypochloremia is a risk factor in the prognosis of heart failure (HF) in patients with recent decompensation., Materials and Methods: retrospective cohort study of patients discharged due to HF decompensation who began follow-up in a specialized clinic. Two groups are defined: patients with hypochloremia (chloride < 98 mmol/L) and normochloremic patients (chloride > 98 mmol/L) in the initial assessment within the first month after discharge. The rate of intravenous diuretic rescue, emergency department visits, readmission for HF and cardiovascular (CV) death are compared using a Cox proportional hazards model., Results: 165 patients were included (59% women, mean age 85 years), with 60 (36%) having hypochloremia. Both groups were comparable in terms of baseline characteristics, except for female sex, presence of peripheral artery disease, moderate-to-severe liver disease (more prevalent in the hypochloremia group), PROFUND index, and baseline furosemide dose (higher in patients with hypochloremia). The incidence of the primary event was higher in subjects with hypochloremia than in normochloremic subjects (HR: 1.59, 95% CI 0.97-2.62), mainly due to the need for intravenous diuretic rescue (HR: 1.86, 95% CI 1.07-3.24)., Conclusions: hypochloremia following admission for HF decompensation is associated with a greater need for intravenous diuretic rescue therapy and probably worse overall prognosis across the spectrum of the disease, regardless of left ventricular ejection fraction (LVEF)., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Up to 50% of patients admitted for heart failure (HF) have congestion at discharge despite diagnostic and therapeutic advances. Both persistent congestion and diuretic resistance are associated with worse prognosis. The combination of hypertonic saline and loop diuretic has shown promising results in different studies. However, it has not yet achieved a standardized use, partly because of the great heterogeneity in the concentration of sodium chloride, the dose of diuretic or the amount of sodium in the diet. Classically, the movement of water from the intracellular space due to an increase in extracellular osmolarity has been postulated as the main mechanism involved. However, chloride deficit is postulated as the main up-regulator of plasma volume changes, and its correction may be the main mechanism involved. This "chloride centric" approach to heart failure opens the door to therapeutic strategies that would include diuretics to correct hypochloremia, as well as sodium free chloride supplementation., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Heart failure (HF) progression according to changes in the serum chloride concentration ([sCl-]) was recently proposed as the "chloride (Cl) theory" for HF pathophysiology. The present study examined the association of neurohormones and renal Cl avidity to determine their contribution to acute HF and their involvement to the "Cl theory.", Methods: Data from 29 patients with acute HF (48% men; 80.3 ± 12 years) were analyzed. Blood and urine samples were obtained before decongestive therapy. Clinical tests included peripheral blood, serum and spot urinary electrolytes, b-type natriuretic peptide (BNP), and plasma neurohormones., Results: In the 29 patients, urinary Cl concentrations ([uCl-]) inversely correlated with log (plasma renin activity [PRA]) (r = -0.64, p = 0.0002) and log (plasma aldosterone concentration) (r = -0.50, p = 0.006). The [sCl-]‒[uCl-] difference positively correlated with log PRA (r = 0.63, p = 0.0002) and log (plasma aldosterone concentration) (r = 0.49, p = 0.008). Patients were divided into 2 groups according to the [sCl-]‒[uCl-] difference, an excretion (low renal Cl avidity) group and an absorption (high renal Cl avidity) group. Compared with the excretion group (-77 to ‒5 mEq/L; n = 14), the absorption group (1-84 mEq/L; n = 15) exhibited greater renal impairment (serum creatinine; 1.45 ± 0.63 vs. 1.00 ± 0.38 mg/d, p = 0.029) and cardiac burden (log BNP; 2.99 ± 0.3 vs. 2.66 ± 0.32 pg/mL, p = 0.008), higher log PRA (0.20 ± 0.58 vs. -0.25 ± 0.35 ng/mL/h, p = 0.018), and lower fractional urinary Cl excretion (1.34 ± 1.3 vs. 5.33 ± 4.1%, p &lt; 0.001)., Conclusion: Renal Cl avidity differs in acute HF, i.e., excretion (low renal Cl avidity) versus absorption (high renal Cl avidity) types, involving renin-aldosterone-angiotensin activity as the underlying mechanism, which provides the neurohormonal background for the "Cl theory." A version of this study was presented in part at the annual international scientific assembly (ACC.23) of the American College of Cardiology, March 4-6, 2023., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Sodium and chloride disturbances have attracted increasing attention in recent years. Many pathophysiological effects are associated with hyperchloremia, including reduction in mean arterial pressure and acute renal disease. Pediatric patients undergoing liver transplantation are at risk of developing various electrolyte and biochemical abnormalities, with an impact on their postoperative outcomes., Objective: To analyze the impacts of serum sodium and chloride levels on prognosis of Pediatric Liver Transplant receptors., Methods: This was a retrospective analytical observational study performed in a single transplant reference center in Sao Paulo, Brazil. Included patients were pediatric patients who underwent liver transplantation between January 2015 and July 2019. Statistical regression analysis and General Estimating Equations analysis were performed to evaluate the impacts of sodium and chloride disturbances on the development of acute renal failure and mortality., Results: A total of 143 patients were included in this study. The main diagnosis was Biliary Atresia (62.9%). Twenty-seven patients died (18.9%), and graft dysfunction was the main cause of death (29.6%). The only variable individually associated with 28-days mortality was PIM-3 score (HR 1.59, CI 95% 1.165-2.177, p = 0.004). Forty-one patients (28.6%) developed moderate or severe AKI. PIM-3 score (OR 3.052, 95% CI 1.56-5.97, p = 0.001), hypernatremia (OR 3.49, 95% CI 1.32-9.23, p = 0.012), and hyponatremia (OR 4.24, 95% CI 1.52-11.85, p = 0.006) were independently associated with the development of moderate/severe AKI., Conclusions: In pediatric patients after liver transplantation, PIM-3 score, and abnormal serum sodium levels were correlated with AKI development., (© 2023. The Author(s).)

Objective: To explore the predictive value of combined detection of serum interleukin-6 (IL-6), chloride (Cl - ), D-dimer and fibrin degradation products (FDP) for severity of acute pancreatitis (AP)., Methods: From December 2020 to March 2022, 132 AP patients who met the criteria for inclusion were screened for retrospective analysis from 292 AP patients admitted in emergency surgery at the First Affiliated Hospital of Zhengzhou University and they were divided into severe acute pancreatitis (SAP) group and non-SAP group, with 63 in SAP group and 69 in non-SAP group, according to classification criteria. The data including lab results, abdominal doppler ultrasound and chest and abdominal CT, etc. The bedside index for severity in acute pancreatitis (BISAP) score was calculated. Multivariate Logistic regression analysis was carried out to find the risk factors for the severity of AP patients. The receiver operator characteristic curve (ROC) was drawn to judge the clinical predictive value of each factor., Results: A total of 132 AP patients were enrolled. The serum IL-6, D-dimer, FDP levels and the BISAP score in SAP group were significantly higher than those in non-SAP group [serum IL-6 (ng/L): 62.73 (21.54, 187.47) vs. 8.22 (4.13, 14.70), D-dimer (mg/L): 5.36 (2.94, 8.25) vs. 0.94 (0.42, 2.21), FDP (mg/L): 13.54 (6.76, 22.45) vs. 3.20 (2.50, 6.10), BISAP score: 2.00 (1.00, 3.00) vs. 1.00 (0, 2.00), all P < 0.05], while the serum Cl - level was significantly lower than that of non-SAP group (mmol/L: 97.90±4.86 vs. 101.73±4.32, P < 0.05). Multivariate Logistic regression analysis showed that increased levels of IL-6 [odds ratio (OR) = 1.02, 95% confidence interval (95%CI) was 1.01-1.04], D-dimer (OR = 1.21, 95%CI was 1.05-1.40) and decreased Cl - level (OR = 0.88, 95%CI was 0.79-0.98) were risk factors for SAP (all P < 0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of IL-6, Cl - , D-dimer and FDP combined to predict the severity of AP patients was larger (0.89), and the sensitivity (82.50%) and specificity (85.50%) were higher., Conclusions: Compared with single index, the combined detection of serum IL-6, Cl - , D-dimer and FDP is more precise in determining the condition of AP.

Background: Serum chloride (Cl - ) is one of the most essential extracellular anions. Based on emerging evidence obtained from patients with kidney or heart disease, hypochloremia has been recognized as an independent predictor of mortality. Nevertheless, excessive Cl - can also cause death in severely ill patients. This study aimed to investigate the relationship between hyperchloremia and high mortality rate in patients admitted to the surgical intensive care unit (SICU)., Methods: We enrolled 2131 patients from the Multiparameter Intelligent Monitoring in Intensive Care III database version 1.4 (MIMIC-III v1.4) from 2001 to 2012. Selected SICU patients were more than 18 years old and survived more than 72 h. A serum Cl - level ≥ 108 mEq/L was defined as hyperchloremia. Clinical and laboratory variables were compared between hyperchloremia (n = 664) at 72 h post-ICU admission and no hyperchloremia (n = 1467). The Locally Weighted Scatterplot Smoothing (Lowess) approach was utilized to investigate the correlation between serum Cl- and the thirty-day mortality rate. The Cox proportional-hazards model was employed to investigate whether serum chlorine at 72 h post-ICU admission was independently related to in-hospital, thirty-day and ninety-day mortality from all causes. Kaplan-Meier curve of thirty-day and ninety-day mortality and serum Cl - at 72 h post-ICU admission was further constructed. Furthermore, we performed subgroup analyses to investigate the relationship between serum Cl - at 72 h post-ICU admission and the thirty-day mortality from all causes., Results: A J-shaped correlation was observed, indicating that hyperchloremia was linked to an elevated risk of thirty-day mortality from all causes. In the multivariate analyses, it was established that hyperchloremia remained a valuable predictor of in-hospital, thirty-day and ninety-day mortality from all causes; with adjusted hazard ratios (95% CIs) for hyperchloremia of 1.35 (1.02 ~ 1.77), 1.67 (1.28 ~ 2.19), and 1.39 (1.12 ~ 1.73), respectively. In subgroup analysis, we observed hyperchloremia had a significant interaction with AKI (P for interaction: 0.017), but there were no interactions with coronary heart disease, hypertension, and diabetes mellitus (P for interaction: 0.418, 0.157, 0.103, respectively)., Conclusion: Hyperchloremia at 72 h post-ICU admission and increasing serum Cl - were associated with elevated mortality risk from all causes in severely ill SICU patients., (© 2022. The Author(s).)

Although hypochloremia is strongly associated with adverse prognosis in acute heart failure (AHF), it is unknown whether incorporating hypochloremia into the preexisting risk model improves the model performance. We calculated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score in 1,428 patients with AHF (derivation cohort) and developed 2 risk scores incorporating brain natriuretic peptide (BNP) into the GWTG-HF risk score (GWTG-BNP risk score) and incorporating both BNP and hypochloremia (GWTG-BNP-Cl risk score). Hypochloremia was defined as <98 mmol/L. The external validation and comparison of model performance were performed in an independent group of 1,256 patients with AHF (validation cohort). All models were tested for in-hospital mortality. Hypochloremia was observed in 9.4% and 12.2% of the derivation and validation cohorts, respectively. Hypochloremia was an independent predictor of in-hospital mortality in the derivation cohort (odds ratio 2.02; p = 0.028). In the validation cohort, the GWTG-HF, GWTG-BNP, and GWTG-BNP-Cl risk scores demonstrated good discrimination (area under the curve: 0.742, 0.749, and 0.763, respectively). However, the GWTG-BNP-Cl risk score was more reliable than the GWTG-HF and GWTG-BNP risk scores in risk reclassification (net reclassification improvement: 0.491 and 0.408, respectively; p <0.01 for both). Moreover, this score demonstrated a good calibration of the GWTG-BNP-Cl model (Hosmer-Lemeshow test: p = 0.479). In conclusion, incorporating hypochloremia into the preexisting risk model improves the model performance., Competing Interests: Disclosures Dr. Yuya Matsue is affiliated to a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi and received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr. Takahiro Okumura received research grants from Ono Pharmaceutical Co., Ltd., Bayer Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharma Inc., and Amgen Astellas BioPharma K.K. outside the submitted work, and received honorariums from Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., and Medtronic Japan Co., Ltd. The other authors have no conlicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 2-week research was carried out to assess water salinity (WS) effects including 0, 15, 35, and 50‰ on osmoregulatory mechanisms and stress indices in Asian sea bass (34.4 g) juveniles. Except for fish reared at 50‰, in the other treatments, it gradually decreased to the prescribed WS during a 10-day period (- 5‰ a day). After a 10-day acclimation period, fish were reared at the prescribed WS for 2 weeks. Fish reared at 15 and 35‰ had higher chloride cell (CC) counts in the interlamellar region. The number of CC in the interlamellar region elevated with increment of WS up to 35‰, but they were pronouncedly reduced in 50‰ group. The diameter of CC in the interlamellar region was not affected by WS. The smallest nucleus diameter of CC in the interlamellar region was observed in fish reared at 15‰ (P < 0.05). The largest and the smallest amounts of serum aspartate aminotransferase were observed in fish reared at freshwater and 15‰, respectively. Fish reared at 35‰ had the highest serum sodium and potassium contents. Serum chloride content and total osmolality increased with increment of WS (P < 0.05). Serum cortisol and glucose contents gradually increased with elevation of WS up to 35‰; then, their contents remarkably decreased. The relative expression of insulin like growth factor-1 in the liver of fish reared at 35‰ was strikingly higher than that in the other groups. The relative expression of HSP70 gene in fresh water group was pronouncedly elevated compared to other treatments. The relative expression of interleukin-1β in 15 and 35‰ groups was higher than that in the other groups; however, the relative expression of lysozyme gene in the liver of fish reared at fresh water was pronouncedly lower than that in the other treatments. The results of this study suggested rearing L. calcarifer at 15‰ closer to the isosmotic point and better provide its welfare., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Positive retests of COVID-19 represent a public health concern because of the increased risk of transmission. This study explored whether factors other than the nucleic acid amplification test (NAAT) contribute to positive retest results. Patients with COVID-19 admitted to the Guanggu district of the Hubei Maternal and Child Health Hospital between February 17 and March 28, 2020, were retrospectively included. The patients were grouped into the negative (n = 133) and positive (n = 51) retest groups. The results showed that the proportion of patients presenting with cough was higher (P < 0.001) and the proportion of patients with dyspnea was lower (P = 0.018) in the positive than in the negative retest group. The positive retest group showed shorter durations between symptom onset and hospitalization (P < 0.001) and symptom onset and the first positive NAAT (P = 0.033). The positive retest group had higher basophil counts (P = 0.023) and direct bilirubin (P = 0.032) and chlorine concentrations (P = 0.023) but lower potassium concentrations (P = 0.001) than the negative retest group. Multivariable regression analysis showed that coughing (OR = 7.59, 95% CI 2.28-25.32, P = 0.001) and serum chloride concentrations (OR = 1.38, 95% CI 1.08-1.77, P = 0.010) were independently associated with a positive retest result. Coughing and serum chloride concentrations were independent risk factors for positive NAAT retest results. Patients with a hospital stay of < 2 weeks or a short incubation period should stay in isolation and be monitored to reduce transmission. These results could help identify patients who require closer surveillance., (© 2021. The Author(s).)

Background: Hyperchloremia is associated with the risks of several morbidities and mortality. However, its relationship with acute kidney injury (AKI) and end-stage renal disease (ESRD) in patients undergoing coronary artery bypass grafting (CABG) remains unresolved., Methods: A total of 2977 patients undergoing CABG between 2003 and 2015 were retrospectively reviewed from two tertiary hospitals. Patients were categorized by serum chloride levels into normochloremia (95-105 mmol/L), mild hyperchloremia (106-110 mmol/L), and severe hyperchloremia (> 110 mmol/L). The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD were calculated after adjustment for multiple covariates. The death-adjusted risk of ESRD was additionally evaluated., Results: Postoperative AKI occurred in 798 patients (26.5%). The hyperchloremia group had a higher risk of AKI than the normochloremia group, wherein the risk was incremental depending on the severity of hyperchloremia, as follows: ORs were 1.26 (1.06-1.51) and 1.95 (1.52-2.51) in the mild and severe hyperchloremia groups, respectively. During a median period of 7 years (maximum 15 years), 70 patients (2.3%) had ESRD. The severe hyperchloremia group was at an elevated risk of ESRD compared with the normochloremia group, with an HR of 2.43 (1.28-4.63). Even after adjusting for the competing risk of death, hyperchloremia was associated with the risk of ESRD., Conclusions: Preoperative hyperchloremia is associated with poor renal outcomes such as AKI and ESRD after CABG. Accordingly, serum chloride should be monitored in patients undergoing CABG., (© 2021. The Author(s).)

The HCO 3 - concentration in venous serum ([HCO 3 - ] s ) is a factor commonly used for detecting the body pH and metabolic conditions. To exactly detect [HCO 3 - ] s , the venous CO 2 pressure should be kept as it is in the vein. The [HCO 3 - ] s measurement is technically complicated to apply for huge numbers of almost heathy persons taking only basic medical examinations. The summation of [HCO 3 - ] s and the venous serum Cl - concentration ([Cl - ] s ) is approximately constant; therefore, we studied if [Cl - ] s could be a marker detecting metabolic conditions instead of [HCO 3 - ] s . Venous blood was obtained from persons taking basic medical examinations (the number of persons = 107,630). Older persons showed higher values of [Cl - ] s , fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) than younger ones. [Cl - ] s showed positive correlation to age and negative correlation to FBS and HBA1c. The negative correlation of [Cl - ] s to FBS/HbA1c was obvious in persons with high FBS/HbA1c, leading us to an idea that persons with high FBS/HbA1c show high [HCO 3 - ] s , which might be caused by low activity of carbonic anhydrase in the lung observed in persons with diabetes mellitus under acidotic conditions. Taken together, an easily measured serum electrolyte, [Cl - ] s , could be a useful marker estimating metabolic conditions.

Introduction: The identification of reliable prognostic factors is a crucial requirement for patients with IgA nephropathy (IgAN). Here, we explored the relationship between serum chloride levels and prognosis in patients with IgAN., Methods: We recruited all patients with primary IgAN, as diagnosed by renal biopsy, between 1 st January 2015 and 1 st April 2019. Patients were divided two groups (high chloride group and low chloride group) based on the best cut-off values from survival receiver operating characteristic (ROC) curves. The baseline clinicopathological characteristics of two groups were then compared. Cox proportional hazard models were used to determine the prognostic value of serum chloride levels in patients with IgAN. Finally, we screened reliable prognostic indicators and built a clinical prediction model and validated the performance of the model., Results: Compared with patients in the high chloride group, patients in the low chloride group had significantly lower levels of 24-hour urinary total protein (24 h-UTP), serum creatinine (sCr), and higher levels of hemoglobin (Hb), albumin (all p < 0.05), and less proportion of Oxford classification grade E1 (endothelial cell proliferation) and T2 (renal tubule atrophy or renal interstitial fibrosis). Cox analysis revealed that serum chloride level ≥ 105.4 mmol/L was a significant and independent risk factor for prognosis in patients with IgAN ( p < 0.05). Serum chloride, sCr, T, hypertension, and Hb were used to generate a predictive model for prognosis. The c -indices of our predictive model were 0.80, 0.86, and 0.78, for 1, 2, and 3 years, respectively; Brier scores were 0.06, 0.09, and 0.16, respectively., Conclusions: A serum chloride level ≥ 105.4 mmol/l was identified as a significant and independent risk factor for the prognosis of patients with IgAN. A predictive prognosis model was generated using serum chloride, sCr, T, hypertension, and Hb; this model exhibited a good predictive effect., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Yaling Zhai et al.)

Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters., Methods: We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 4289 hospitalized adult patients with acute kidney injury at admission. The standardized difference of each variable was calculated to identify each cluster's key features. We assessed the association of each acute kidney injury cluster with hospital and one-year mortality., Results: Consensus clustering analysis identified four distinct clusters. There were 1201 (28%) patients in cluster 1, 1396 (33%) patients in cluster 2, 1191 (28%) patients in cluster 3, and 501 (12%) patients in cluster 4. Cluster 1 patients were the youngest and had the least comorbidities. Cluster 2 and cluster 3 patients were older and had lower baseline kidney function. Cluster 2 patients had lower serum bicarbonate, strong ion difference, and hemoglobin, but higher serum chloride, whereas cluster 3 patients had lower serum chloride but higher serum bicarbonate and strong ion difference. Cluster 4 patients were younger and more likely to be admitted for genitourinary disease and infectious disease but less likely to be admitted for cardiovascular disease. Cluster 4 patients also had more severe acute kidney injury, lower serum sodium, serum chloride, and serum bicarbonate, but higher serum potassium and anion gap. Cluster 2, 3, and 4 patients had significantly higher hospital and one-year mortality than cluster 1 patients ( p < 0.001)., Conclusion: Our study demonstrated using machine learning consensus clustering analysis to characterize a heterogeneous cohort of patients with acute kidney injury on hospital admission into four clinically distinct clusters with different associated mortality risks.

Objectives: Diabetic ketoacidosis (DKA) is typically characterized by low or low-normal serum sodium concentrations, which rise as hyperglycemia resolves. In retrospective studies, researchers found associations between declines in sodium concentrations during DKA and cerebral injury. We prospectively investigated determinants of sodium concentration changes and associations with mental status alterations during DKA., Methods: Using data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis Trial, we compared children who had declines in glucose-corrected sodium concentrations with those who had rising or stable concentrations. Children were randomly assigned to 1 of 4 intravenous fluid protocols that differed in infusion rate and sodium content. Data from the first 4, 8, and 12 hours of treatment were analyzed for 1251, 1086, and 877 episodes, respectively., Results: In multivariable analyses, declines in glucose-corrected sodium concentrations were associated with higher sodium and chloride concentrations at presentation and with previously diagnosed diabetes. Treatment with 0.45% (vs 0.9%) sodium chloride fluids was also associated with declines in sodium concentration; however, higher rates of fluid infusion were associated with declines in sodium concentration only at 12 hours. Frequencies of abnormal Glasgow Coma Scale scores and clinical diagnoses of cerebral injury were similar in patients with and without declines in glucose-corrected sodium concentrations., Conclusions: Changes in glucose-corrected sodium concentrations during DKA treatment are influenced by the balance of free-water loss versus sodium loss at presentation and the sodium content of intravenous fluids. Declines in glucose-corrected sodium concentrations are not associated with mental status changes during treatment., Competing Interests: POTENTIAL CONFLICTS OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: Pseudohyperchloremia results in a very low or negative anion gap. Historically, the most common cause of this artifact was bromide poisoning. Bromide salts have been removed from most medications and bromism has become very uncommon. More recently, the introduction of chloride ion selective sensing electrodes (Cl-ISE) has generated a new cause of pseudohyperchloremia-salicylate poisoning. We describe 5 such patients and quantitate the error generated by this measurement artifact., Methods: The magnitude of artifactual hyperchloremia generated by high salicylate levels was quantified in 5 patients by measuring chloride concentration with several Cl-ISEs from different manufacturers and with Cl-ISEs of different "ages," and comparing these results to measurements with a chloridometer (coulometric titration), which is free of the salicylate artifact., Results: Cl-ISEs from different manufacturers generated a wide range of artifactual chloride concentration elevation. Furthermore, the same Cl-ISE generated increasingly severe pseudohyperchloremia as it was repeatedly reused over time and "aged.", Conclusions: Salicylate interferes with measurement of the blood chloride concentration when a Cl-ISE is used. The severity of this artifact is related to the salicylate level, the specific Cl-ISE, and the "age" of the electrode. Toxic blood salicylate levels can generate marked pseudohyperchloremia, and consequently, an artifactual very small or negative anion gap. The large anion gap metabolic acidosis typical of salicylate poisoning is masked by this artifact. Salicylate has become the most common cause of pseudohyperchloremia, and physicians should immediately consider salicylate poisoning whenever the combination of hyperchloremia and a very small or negative anion gap is reported by the laboratory., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Intravenous magnesium sulfate (MgSO4) is used in equine practice to treat hypomagnesemia, dysrhythmias, neurological disorders, and calcium dysregulation. MgSO4 is also used as a calming agent in equestrian events. Hypercalcemia affects calcium-regulating hormones, as well as plasma and urinary electrolytes; however, the effect of hypermagnesemia on these variables is unknown. The goal of this study was to investigate the effect of hypermagnesemia on blood parathyroid hormone (PTH), calcitonin (CT), ionized calcium (Ca2+), ionized magnesium (Mg2+), sodium (Na+), potassium (K+), chloride (Cl-) and their urinary fractional excretion (F) after intravenous administration of MgSO4 in healthy horses. Twelve healthy female horses of 4-18 years of age and 432-600 kg of body weight received a single intravenous dose of MgSO4 (60 mg/kg) over 5 minutes, and blood and urine samples were collected at different time points over 360 minutes. Plasma Mg2+ concentrations increased 3.7-fold over baseline values at 5 minutes and remained elevated for 120 minutes (P < 0.05), Ca2+ concentrations decreased from 30-60 minutes (P < 0.05), but Na+, K+ and Cl- concentrations did not change. Serum PTH concentrations dropped initially to rebound and remain elevated from 30 to 60 minutes, while CT concentrations increased at 5 minutes to return to baseline by 10 minutes (P < 0.05). The FMg, FCa, FNa, FK, and FCl increased, while urine osmolality decreased from 30-60 minutes compared baseline (P < 0.05). Short-term experimental hypermagnesemia alters calcium-regulating hormones (PTH, CT), reduces plasma Ca2+ concentrations, and increases the urinary excretion of Mg2+, Ca2+, K+, Na+ and Cl- in healthy horses. This information has clinical implications for the short-term effects of hypermagnesemia on calcium-regulation, electrolytes, and neuromuscular activity, in particular with increasing use of Mg salts to treat horses with various acute and chronic conditions as well as a calming agent in equestrian events., Competing Interests: Dr. Stephen Schumacher is employed by the sponsor of the project (USEF). However, this affiliation does not alter our adherence to all PLOS ONE policies on sharing data and materials.

Titanium dioxide nanoparticles (TiO 2 ) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO 2 ) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO 2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO 2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO 2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Meryem Bakour et al.)

Objectives: Hyperchloraemia is associated with poor clinical outcomes in sepsis patients; however, this association is not well studied for hypochloraemia. We investigated the prevalence of chloride imbalance and the association between hypochloraemia and 28-day mortality in ED patients with septic shock., Methods: A retrospective analysis of data from 11 multicentre EDs in the Republic of Korea prospectively collected from October 2015 to April 2018 was performed. Initial chloride levels were categorised as hypochloraemia, normochloraemia and hyperchloraemia, according to sodium chloride difference adjusted criteria. The primary outcome was 28-day mortality. A multivariate logistic regression model adjusting for age, sex, comorbidities, acid-base state, sepsis-related organ failure assessment (SOFA) score, lactate and albumin level was used to test the association between the three chloride categories and 28-day mortality., Results: Among 2037 enrolled patients, 394 (19.3%), 1582 (77.7%) and 61 (3.0%) patients had hypochloraemia, normochloraemia and hyperchloraemia, respectively. The unadjusted 28-day mortality rate in patients with hypochloraemia was 27.4% (95% CI, 23.1% to 32.1%), which was higher than in patients with normochloraemia (19.7%; 95% CI, 17.8% to 21.8%). Hypochloraemia was associated with an increase in the risk of 28-day mortality (adjusted OR (aOR), 1.36, 95% CI, 1.00 to 1.83) after adjusting for confounders. However, hyperchloraemia was not associated with 28-day mortality (aOR 1.35, 95% CI, 0.82 to 2.24)., Conclusion: Hypochloraemia was more frequently observed than hyperchloraemia in ED patients with septic shock and it was associated with 28-day mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Chloride is an important electrolyte in the body. In this study, we aimed to evaluate the associations between chloride levels on emergency department (ED) admission and neurologic outcomes by stratifying patients undergoing targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) into three groups (hyper/normo/hypochloremia); we also assessed the effect of changes in chloride levels from baseline over time on outcomes., Methods: This retrospective, observational cohort study of 346 patients was conducted between 2011 and 2019. The chloride levels were categorized as hypochloremia, normochloremia, and hyperchloremia by predetermined definitions. The primary endpoint was poor neurologic outcomes after hospital discharge. We evaluated the associations between chloride levels on ED admission and neurologic outcomes and assess the effect of changes in chloride levels over time on clinical outcomes., Results: On ED admission, compared with normochloremia, hypochloremia was significantly associated with unfavorable neurologic outcomes (OR, 2.668; 95% CI, 1.217-5.850, P = 0.014). Over time, unfavorable neurologic outcomes were significantly associated with increases in chloride levels in the hyperchloremia and normochloremia groups after ED admission. The rates of poor neurologic outcomes in the hyperchloremia and normochloremia groups were increased by 14.2% at Time-12, 20.1% at Time-24, and 9.3% at Time-48 with a 1-mEq/L increase in chloride levels., Conclusion: In clinical practice, chloride levels can be routinely and serially measured cost-effectively. Thus, baseline chloride levels may be a promising tool for rapid risk stratification of patients after OHCA. For fluid resuscitation after cardiac arrest, a chloride-restricted solution may be an early therapeutic strategy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease., Subjects and Methods: Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney stones were prospectively collected between April 2011 and February 2017. Data were analysed to determine the utility of serum calcium, parathyroid hormone (PTH), urate, chloride, bicarbonate, potassium and phosphate assays in screening for primary hyperparathyroidism, normocalcaemic hyperparathyroidism, hyperuricosuria, distal renal tubular acidosis (dRTA) and hypercalciuria., Results: An elevated serum calcium level was detected in 2.3% of patients. Further investigations prompted by this finding resulted in a diagnosis of primary hyperparathyroidism in 0.2% of men and 4.6% of women for whom serum calcium was recorded. An elevated serum PTH level in the absence of hypercalcaemia was detected in 15.1% of patients. Of these patients, 74.6% were vitamin D-insufficient; no patients were diagnosed with normocalcaemic hyperparathyroidism. Hyperuricosuria was present in 21.6% of patients and hypercalciuria in 47.1%. Hyperuricaemia was not associated with hyperuricosuria, nor was hypophosphataemia associated with hypercalciuria. No patient was highlighted as being at risk of dRTA using serum chloride and bicarbonate as screening tests., Conclusion: This study indicates that individuals presenting with renal calculi should undergo metabolic screening with a serum calcium measurement alone. Use of additional blood tests to screen for metabolic disorders is not cost-effective and may provide false reassurance that metabolic abnormalities are not present. A full metabolic assessment with 24-h urine collection should be undertaken in recurrent stone formers and in those at high risk of future stone disease to identify potentially treatable metabolic abnormalities., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Purpose: We recently demonstrated that coingestion of NaHCO3 to counteract ketoacidosis resulting from oral ketone ester (KE) intake improves mean power output during a 15-min time trial (TT) at the end of a 3-h cycling race by ~5%. This ergogenic effect occurred at a time when blood ketone levels were low, as ketosis was only induced during the initial ~2 h of the race. Therefore, in the current study, we investigated whether performance also increases if blood ketone levels are increased in the absence of ketoacidosis during high-intensity exercise., Methods: In a double-blind crossover design, 14 well-trained male cyclists completed a 30-min TT (TT30') followed by an all-out sprint at 175% of lactate threshold (SPRINT). Subjects were randomized to receive (i) 50 g KE, (ii) 180 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON)., Results: KE ingestion increased blood d-ß-hydroxybutyrate to ~3-4 mM during the TT30' and SPRINT (P < 0.001 vs CON). In KE, blood pH and bicarbonate concomitantly dropped, causing 0.05 units lower pH and 2.6 mM lower bicarbonate in KE compared with CON during the TT30' and SPRINT (P < 0.001 vs CON). BIC coingestion resulted in 0.9 mM higher blood d-ß-hydroxybutyrate (P < 0.001 vs KE) and completely counteracted ketoacidosis during exercise (P > 0.05 vs CON). Mean power output during TT30' was similar between CON and BIC at 281 W, but was 1.5% lower in the KE conditions (main effect of KE: P = 0.03). Time to exhaustion in the SPRINT was ~64 s in CON and KE and increased by ~8% in the BIC conditions (main effect of BIC: P < 0.01)., Discussion: Neutralization of acid-base disturbance by BIC coingestion is insufficient to counteract the slightly negative effect of KE intake during high-intensity exercise., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

To practically determine the effect of chloride (Cl) on the acid-base status, four approaches are currently used: accepted ranges of serum Cl values; Cl corrections; the serum Cl/Na ratio; and the serum Na-Cl difference. However, these approaches are governed by different concepts. Our aim is to investigate which approach to the evaluation of the effect of Cl is the best. In this retrospective cohort study, 2529 critically ill patients who were admitted to the tertiary care unit between 2011 and 2018 were retrospectively evaluated. The effects of Cl on the acid-base status according to each evaluative approach were validated by the standard base excess (SBE) and apparent strong ion difference (SIDa). To clearly demonstrate only the effects of Cl on the acid-base status, a subgroup that included patients with normal lactate, albumin and SIG values was created. To compare approaches, kappa and a linear regression model for all patients and Bland-Altman test for a subgroup were used. In both the entire cohort and the subgroup, correlations among BECl, SIDa and SBE were stronger than those for other approaches (r = 0.94 r = 0.98 and r = 0.96 respectively). Only BECl had acceptable limits of agreement with SBE in the subgroup (bias: 0.5 mmol L-1) In the linear regression model, only BECl in all the Cl evaluation approaches was significantly related to the SBE. For the evaluation of the effect of chloride on the acid-base status, BECl is a better approach than accepted ranges of serum Cl values, Cl corrections and the Cl/Na ratio., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We sought to describe the association between serum chloride levels and mortality among unselected cardiac intensive care unit (CICU) patients., Materials and Methods: We retrospectively reviewed adult patients admitted to our CICU from 2007 to 2015. The association of dyschloremia and hospital mortality was assessed in a multiple variable model including additional confounders, and the association of dyschloremia and post-discharge mortality were assessed using Cox proportional-hazards analysis., Results: 9,426 patients with a mean age of 67±15 years (37% females) were included. Admission hypochloremia was present in 1,384 (15%) patients, and hyperchloremia was present in 1,606 (17%) patients. There was a U-shaped relationship between admission chloride and unadjusted hospital mortality, with increased hospital mortality among patients with hypochloremia (unadjusted OR 3.0, 95% CI 2.5-3.6, p<0.001) or hyperchloremia (unadjusted OR 1.9, 95% CI 1.6-2.3, p<0.001). After multivariate adjustment, hypochloremia remained associated with higher hospital mortality (adjusted OR 2.1, 95% CI 1.6-2.9, p <0.001). Post-discharge mortality among hospital survivors was higher among patients with admission hypochloremia (adjusted HR 1.3, 95% CI 1.1-1.6; p<0.001)., Conclusion: Abnormal serum chloride on admission to the CICU is associated with increased short- and long-term mortality, with hypochloremia being a strong independent predictor., Competing Interests: The authors have declared that no competing interests exist.

Background: Isotonic saline (IS) is widely used to secure perioperative cardiovascular stability. However, the high amount of chloride in IS can induce hyperchloremic acidosis. Therefore, IS is suspected to increase the risk of acute kidney injury (AKI). Biomarkers may have potential as indicators., Methods: In a double-blinded, placebo-controlled study, 38 patients undergoing primary uncemented hip replacement were randomized to IS or PlasmaLyte (PL). Infusion was given during surgery as 15 ml/kg the first hour and 5 ml/kg the following two hours. Urinary samples were collected upon admission and the day after surgery. As surgery was initiated, urine was collected over the course of 4 h. Hereafter, another urine collection proceeded until the morning. Urine was analyzed for markers of AKI neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Arterious and venous blood samples for measurements of pH and plasma electrolytes including chloride (p-Cl) were collected as surgery was initiated, at the end of surgery and the following morning., Results: IS induced an increase in p-Cl (111 ± 2 mmol/L after IS and 108 ± 3 after PL, p = 0.004) and a decrease in pH (7.39 ± 0.02 after IS and 7.43 ± 0.03 after PL, p = 0.001). Urinary NGAL excretion increased in both groups (ΔNGAL: 5.5 [4.1; 11.7] μg/mmol creatinine p = 0.004 after IS vs. 5.5 [2.1;9.4] μg/mmol creatinine after PL, p < 0.001). No difference was found between the groups (p = 0.839). Similarly, urinary KIM-1 excretion increased in both groups (ΔKIM-1: IS 115.8 [74.1; 156.2] ng/mmol creatinine, p < 0.001 vs. PL 152.4 [120.1; 307.9] ng/mmol creatinine, p < 0.001). No difference between the groups (p = 0.064). FE Na increased (1.08 ± 0.52% after IS and 1.66 ± 1.15% after PL, p = 0.032). ENaC excretion was different within groups (p = 0.019)., Conclusion: A significantly higher plasma chloride and a lower pH was present in the group receiving isotonic saline. However, u-NGAL and u-KIM-1 increased significantly in both groups after surgery despite absence of changes in creatinine. These results indicate that surgery induced subclinical kidney injury. Also, the IS group had a delayed sodium excretion as compared to the PL group which may indicate that IS affects renal sodium excretion differently from PL., Trial Registration: ClinicalTrials.gov Identifier:  NCT02528448 , 19/08/2015.

Background: Muscle cramp is a painful, involuntary muscle contraction, and that occurs during or following exercise is referred to as exercise-associated muscle cramp (EAMC). The causes of EAMC are likely to be multifactorial, but dehydration and electrolytes deficits are considered to be factors. This study tested the hypothesis that post-exercise muscle cramp susceptibility would be increased with spring water ingestion, but reduced with oral rehydration solution (ORS) ingestion during exercise., Methods: Ten men performed downhill running (DHR) in the heat (35-36 °C) for 40-60 min to reduce 1.5-2% of their body mass in two conditions (spring water vs ORS) in a cross-over design. The body mass was measured at 20 min and every 10 min thereafter during DHR, and 30 min post-DHR. The participants ingested either spring water or ORS for the body mass loss in each period. The two conditions were counter-balanced among the participants and separated by a week. Calf muscle cramp susceptibility was assessed by a threshold frequency (TF) of an electrical train stimulation to induce cramp before, immediately after, 30 and 65 min post-DHR. Blood samples were taken before, immediately after and 65 min after DHR to measure serum sodium, potassium, magnesium and chroride concentrations, hematocrit (Hct), hemoglobin (Hb), and serum osmolarity. Changes in these varaibles over time were compared between conditions by two-way repeated measures of analysis of variance., Results: The average (±SD) baseline TF (25.6 ± 0.7 Hz) was the same between conditions. TF decreased 3.8 ± 2.7 to 4.5 ± 1.7 Hz from the baseline value immediately to 65 min post-DHR for the spring water condition, but increased 6.5 ± 4.9 to 13.6 ± 6.0 Hz in the same time period for the ORS condition (P < 0.05). Hct and Hb did not change significantly (P > 0.05) for both conditions, but osmolarity decreased (P < 0.05) only for the spring water condition. Serum sodium and chloride concentrations decreased (< 2%) at immediately post-DHR for the spring water condition only (P < 0.05)., Conclusions: These results suggest that ORS intake during exercise decreased muscle cramp susceptibility. It was concluded that ingesting ORS appeared to be effective for preventing EAMC.

Purpose: To reduce the need for invasive and expensive measures of human biomarkers, sweat is becoming increasingly popular in use as an alternative to blood. Therefore, the (in)dependency of blood and sweat composition has to be explored., Methods: In an environmental chamber (33 °C, 65% relative humidity; RH), 12 participants completed three subsequent 20-min cycling stages to elicit three different local sweat rates (LSR) while aiming to limit changes in blood composition: at 60% of their maximum heart rate (HR max ), 70% HR max and 80% HR max , with 5 min of seated-rest in between. Sweat was collected from the arm and back during each stage and post-exercise. Blood was drawn from a superficial antecubital vein in the middle of each stage. Concentrations of sodium, chloride, potassium, ammonia, lactate and glucose were determined in blood plasma and sweat., Results: With increasing exercise intensity, LSR, sweat sodium, chloride and glucose concentrations increased (P ≤ 0.026), while simultaneously limited changes in blood composition were elicited for these components (P ≥ 0.093). Sweat potassium, lactate and ammonia concentrations decreased (P ≤ 0.006), while blood potassium decreased (P = 0.003), and blood ammonia and lactate concentrations increased with higher exercise intensities (P = 0.005; P = 0.007, respectively). The vast majority of correlations between blood and sweat parameters were non-significant (P > 0.05), with few exceptions., Conclusion: The data suggest that sweat composition is at least partly independent of blood composition. This has important consequences when targeting sweat as non-invasive alternative for blood measurements.

The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m 2 . The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.

Aim: Prolonged postoperative ileus (PPOI) occurs in around 15% of patients after major abdominal surgery, posing a significant clinical and economic burden. Significant fluid and electrolyte changes may occur peri-operatively, potentially contributing to PPOI; however, this association has not been clearly elucidated. A joint clinical-theoretical study was undertaken to evaluate peri-operative electrolyte concentration trends, their association with ileus, and predicted impact on bioelectrical slow waves in interstitial cells of Cajal (ICC) and smooth muscle cells (SMC)., Methods: Data were prospectively collected from 327 patients undergoing elective colorectal surgery. Analyses were performed to determine associations between peri-operative electrolyte concentrations and prolonged ileus. Biophysically based ICC and SMC mathematical models were adapted to evaluate the theoretical impacts of extracellular electrolyte concentrations on cellular function., Results: Postoperative day (POD) 1 calcium and POD 3 chloride, sodium were lower in the PPOI group (p < 0.05), and POD3 potassium was higher in the PPOI group (p < 0.05). Deficits beyond the reference range in PPOI patients were most notable for sodium (Day 3: 29.5% ileus vs. 18.5% no ileus, p = 0.04). Models demonstrated an 8.6% reduction in slow-wave frequency following the measured reduction in extracellular NaCl on POD5, with associated changes in cellular slow-wave morphology and amplitude., Conclusion: Low serum sodium and chloride concentrations are associated with PPOI. Electrolyte abnormalities are unlikely to be a primary mechanism of ileus, but their pronounced effects on cellular electrophysiology predicted by modeling suggest these abnormalities may adversely impact motility recovery. Resolution and correction of electrolyte abnormalities in ileus may be clinically relevant., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To determine the significance and impact of additional chloride testing as part of a diagnostic laboratory test battery for borderline primary hyperparathyroidism (pHPT)., Study Design: Retrospective database review of parathyroidectomy patients., Setting: A tertiary care, academic health sciences center., Subjects and Methods: Patients referred to a head and neck endocrine clinic for evaluation and treatment for pHPT., Results: After exclusions, there were a total of 226 patients who underwent parathyroidectomy for primary hyperparathyroidism with the requisite preoperative and postoperative labs. Seventy-seven additional patients who had a thyroid operation for a nonmalignant cause were included as controls. Of the 303 total patients, 166 had normal calcium levels (<10.4 mg/dL), and 54 (32.5%) also exhibited hyperchloremia (>106 mmol/L). Of the 47 patients with normal calcium and parathyroid hormone (PTH) levels (<88 pg/mL), 6 (12.8%) had hyperchloremia, and of the 118 patients with normocalcemic pHPT, 48 (40.7%) were hyperchloremic. The area under the curve for the Cl:PO4 was 0.712. When using a cutoff of 33, the reported sensitivity and specificity of the curve were 58.4% and 28.6%, respectively., Conclusion: The Cl:PO4 ratio was a moderately sensitive test for the diagnosis of the borderline variants of primary hyperparathyroidism. The Ca:PO4 ratio was superior to the Cl:PO4 ratio. Our data also showed the superiority of preoperative calcium and ionized calcium over PTH when predicting the presence of pHPT.