Inverse association between serum chloride levels and the risk of atrial fibrillation in chronic kidney disease patients.

Background: Electrolyte abnormalities are common symptoms of chronic kidney disease (CKD), but previous studies have mainly focussed on serum potassium and sodium levels. Chloride is an important biomarker for the prognosis of various diseases. However, the relationship between serum chloride levels and atrial fibrillation (AF) in CKD patients is unclear. Objective: In this study, we sought to determine the association between serum chloride homeostasis and AF in CKD patients. Methods: In this retrospective cohort study, we included patients who met the diagnostic criteria for CKD in China between 2000 and 2021. Competing risk regression for AF was performed. The associations of the baseline serum chloride concentration with heart failure (HF) and stroke incidence were also calculated by competing risk regression. The association of baseline serum chloride levels with all-cause death was determined by a Cox regression model. Results: The study cohort comprised 20 550 participants. During a median follow-up of 350 days (interquartile range, 123-730 days), 211 of the 20 550 CKD patients developed AF. After multivariable adjustment, every decrease in the standard deviation of serum chloride (5.02 mmol/l) was associated with a high risk for AF [sub-hazard ratio (sHR) 0.78, 95% confidence interval (CI) 0.65-0.94, P = .008]. These results were also consistent with those of the stratified and sensitivity analyses. According to the fully adjusted models, the serum chloride concentration was also associated with a high risk for incident HF (sHR 0.85, 95% CI 0.80-0.91, P < .001), a high risk for incident stroke (sHR 0.87, 95% CI 0.81-0.94, P < .001), and a high risk for all-cause death [hazard ratio (HR) 0.82, 95% CI 0.73-0.91, P < .001]. Conclusion: In this CKD population, serum chloride levels were independently and inversely associated with the incidence of AF. Lower serum chloride levels were also associated with an increased risk of incident HF, stroke, and all-cause death.

L-shaped association between serum chloride levels with 90-day and 365-day all-cause mortality in critically ill patients with COPD: a retrospective cohort study.

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.

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

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).

Predictive value of the prognostic nutritional index combined with serum chloride levels for the prognosis of patients with acute decompensated heart failure.

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 χ2 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.

Association between normal saline infusion volume in the emergency department and acute kidney injury in heat stroke patients: a multicenter retrospective study.

BACKGROUND: Previous studies have shown that intravenous normal saline (NS) may be associated with the incidence of acute kidney injury (AKI). This study aimed to evaluate the association between the volume of NS infusion and AKI in heat stroke (HS) patients. METHODS: This multicenter retrospective cohort study included 138 patients with HS. The primary outcome was the incidence of AKI. Secondary outcomes included the need for continuous renal replacement therapy (CRRT), admission to the intensive care unit (ICU), length of stay in the ICU and hospital, and in-hospital mortality. Multivariate regression models, random forest imputation, and genetic and propensity score matching were used to explore the relationship between NS infusion and outcomes. RESULTS: The mean volume of NS infusion in the emergency department (ED) was 3.02 ± 1.45 L. During hospitalization, 33 patients (23.91%) suffered from AKI. In the multivariate model, as a continuous variable (per 1 L), the volume of NS infusion was associated with the incidence of AKI (OR, 2.51; 95% CI, 1.43-4.40; p = .001), admission to the ICU (OR, 3.46; 95% CI 1.58-7.54; p = .002), and length of stay in the ICU (ß, 1.00 days; 95% CI, 0.44-1.56; p < .001) and hospital (ß, 1.41 days; 95% CI, 0.37-2.45; p = .008). These relationships also existed in the forest imputation cohort and matching cohort. There were no differences in the use of CRRT or in-hospital mortality. CONCLUSIONS: The volume of NS infusion was associated with a significant increase in the incidence of AKI, admission to the ICU, and length of stay in the ICU and hospital among patients with HS.

The association between serum chloride and mortality in ICU patients with heart failure: The impact of bicarbonate.

OBJECTIVE: To assess whether serum chloride predicts risk of death in intensive care unit (ICU) patients with heart failure (HF) and the effect of bicarbonate on the efficacy of serum chloride in predicting risk of death in ICU patients. METHODS: A total of 9364 HF patients hospitalized in the ICU were enrolled. Patients were divided into hypochloremia (< 96 mEq/L), normal chloride (96-108 mEq/L), and hyperchloremia (> 108 mEq/L) groups. Similarly, we divided the serum bicarbonate level into three groups: low bicarbonate (< 22 mEq/L), medium bicarbonate (22-26 mEq/L), and high bicarbonate (> 26 mEq/L). The outcome of this study was in-hospital mortality. Then, we analyzed the association between abnormal serum chloride and mortality according to the category of serum bicarbonate and assessed the interaction effect. Restricted cubic spline (RCS) was used to show possible nonlinear associations. RESULTS: In the overall study population, hypochloremia was associated with a higher risk of in-hospital mortality than normal chloride (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.26-1.86, P < 0.001), hyperchloremia was not significantly related to in-hospital mortality (OR 1.00, 95% CI 0.85-1.19, P = 0.962). However, a linear association between serum chloride and in-hospital mortality was found in the low and normal bicarbonate groups (all P for nonlinear >0.05). CONCLUSIONS: Hypochloremia is associated with in-hospital mortality and longer hospital stay in critically ill patients with HF. In addition, risk of death in the low and medium serum bicarbonate groups decreased with increasing serum chloride level.

L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study.

BACKGROUND: Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. OBJECTIVE: This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. METHODS: Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. RESULTS: A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). CONCLUSIONS: In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.

Serum chloride as a respiratory failure marker in amyotrophic lateral sclerosis.

Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carbonate (HCO3-) blood levels and reflect metabolic compensation of respiratory acidosis. Despite its wide availability and low cost, few data on serum chloride as a prognostic marker exist in ALS literature. In the present study, we evaluated serum chloride values at diagnosis as prognostic biomarkers for overall survival and NIV adaptation in a retrospective center-based cohort of ALS patients. We collected all ALS patients with serum chloride assessment at diagnosis, identified through the Piemonte and Valle d'Aosta Register for ALS, evaluating the correlations among serum chloride, clinical features, and other serum biomarkers. Thereafter, time-to-event analysis was modeled to predict overall survival and NIV start. We found a significant correlation between serum chloride and inflammatory status markers, serum sodium, forced vital capacity (FVC), ALS functional rating scale-revised (ALSFRS-R) item 10 and 11, age at diagnosis, and weight loss. Time-to-event analysis confirmed both in univariate analysis and after multiple confounders' adjustment that serum chloride value at diagnosis significantly influenced survival and time to NIV start. According to our analysis, based on a large ALS cohort, we found that serum chloride analyzed at diagnosis is a low-cost marker of impending respiratory decompensation. In our opinion, it should be added among the serum prognostic biomarkers that are able to stratify patients into different prognostic categories even when performed in the early phases of the disease.

Prognosis value of serum chloride on 1-year mortality in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt.

BACKGROUND AND PURPOSE: Emerging researches have regarded serum chloride as a capable predictor of mortality in liver cirrhosis. We aim to investigate the clinical role of admission chloride in cirrhotic patients with esophagogastric varices receiving transjugular intrahepatic portosystemic shunt (TIPS), which is unclear. METHODS: We retrospectively analyzed data of cirrhotic patients with esophagogastric varices undergoing TIPS in Zhongnan Hospital of Wuhan University. Mortality outcome was obtained by following up for 1-year after TIPS. Univariate and multivariate Cox regression were used to identify independent predictors of 1-year mortality post-TIPS. The receiver operating characteristic (ROC) curves were adopted to assess the predictive ability of the predictors. In addition, log-rank test and Kaplan-Meier (KM) analyses were employed to evaluate the prognostic value of predictors in the survival probability. RESULTS: A total of 182 patients were included ultimately. Age, fever symptom, platelet-to lymphocyte-ratio (PLR), lymphocyte-to-monocyte ratio (LMR), total bilirubin, serum sodium, chloride, and Child-Pugh score were related to 1-year follow-up mortality. In multivariate Cox regression analysis, serum chloride (HR = 0.823, 95%CI = 0.757-0.894, p < 0.001) and Child-Pugh score (HR = 1.401, 95%CI = 1.151-1.704, p = 0.001) were identified as independent predictors of 1-year mortality. Patients with serum chloride <107.35 mmol/L showed worse survival probability than those with serum chloride ≥107.35 mmol/L no matter with or without ascites (p < 0.05). CONCLUSION: Admission hypochloremia and increasing Child-Pugh score are independent predictors of 1-year mortality in cirrhotic patients with esophagogastric varices receiving TIPS.

Persistent Hypochloremia Is Associated with Adverse Prognosis in Patients Repeatedly Hospitalized for Heart Failure.

BACKGROUND: Hypochloremia reflects neuro-hormonal activation in patients with heart failure (HF). However, the prognostic impact of persistent hypochloremia in those patients remains unclear. METHODS: We collected the data of patients who were hospitalized for HF at least twice between 2010 and 2021 (n = 348). Dialysis patients (n = 26) were excluded. The patients were divided into four groups based on the absence/presence of hypochloremia (<98 mmol/L) at discharge from their first and second hospitalizations: Group A (patients without hypochloremia at their first and second hospitalizations, n = 243); Group B (those with hypochloremia at their first hospitalization and without hypochloremia at their second hospitalization, n = 29); Group C (those without hypochloremia at their first hospitalization and with hypochloremia at their second hospitalization, n = 34); and Group D (those with hypochloremia at their first and second hospitalizations, n = 16). RESULTS: a Kaplan-Meier analysis revealed that all-cause mortality and cardiac mortality were the highest in Group D compared to the other groups. A multivariable Cox proportional hazard analysis revealed that persistent hypochloremia was independently associated with both all-cause death (hazard ratio 3.490, p < 0.001) and cardiac death (hazard ratio 3.919, p < 0.001). CONCLUSIONS: In patients with HF, prolonged hypochloremia over two hospitalizations is associated with an adverse prognosis.

Renin-angiotensin system inhibitor exerts prognostic effects in HFpEF patients with low baseline chloride level.

BACKGROUND: Few interventions have shown improved prognosis in patients with heart failure and preserved ejection fraction (HFpEF). Serum chloride levels, which are affected by serum renin secretion, are associated with the prognosis of HFpEF patients. However, the relationship between serum chloride levels and the effects of renin-angiotensin system inhibitors (RASi) in HFpEF patients remains unclear. We investigated whether the prognostic benefit of RASi depends on baseline serum chloride levels in HFpEF patients. METHODS: This observational study included 506 hospitalized patients with HFpEF (ejection fraction ≥50%) who were discharged. They were divided into two categories based on serum chloride levels at admission (cutoff level: 101 mEq/L) according to previous reports. In each chloride category, all-cause mortality, the primary endpoint, was compared between patients who received RASi and those who did not. RESULTS: Patients who received RASi had a significantly lower mortality rate after discharge than those who did not, but only in the lower chloride category (log-rank, P = 0.001). Multivariable Cox regression analysis confirmed the effect of risk reduction by RASi on all-cause mortality in the lower chloride category (adjusted hazard ratio: 0.31, 95% confidence interval: 0.11-0.84). The prognostic advantages of RASi were evident in the lower chloride category, but not in the higher chloride category, at admission (P for interaction = 0.027). CONCLUSION: RASi administration was associated with an improved prognosis only in HFpEF patients with a low baseline serum chloride level. Clinicians should consider RASi administration if patients' serum chloride levels are low, to improve the long-term prognosis of HFpEF patients.

Associations between serum electrolyte and short-term outcomes in patients with acute decompensated heart failure.

INTRODUCTION: There is a dearth of comprehensive studies on the association between serum electrolyte and adverse short-term prognosis of Chinese patients with acute decompensated heart failure (ADHF). PATIENTS AND METHODS: A total of 5166 patients with ADHF were divided into four serum electrolyte-related study populations (potassium (n = 5145), sodium (n = 5135), chloride (n = 4966), serum total calcium (STC) (n = 4143)) under corresponding exclusions. Different logistic regression models were utilized to gauge the association between these electrolytes or the number of electrolyte abnormalities and the risk of a composite of all-cause mortality or 30-day heart failure (HF) readmission. RESULTS: In multivariable adjusted analysis, patients with potassium below 3.5 mmol/L (odds ratios (ORs) 1.45; 95% confidence interval (CI):1.07-1.95), 4.01-4.50 mmol/L (OR: 1.29, CI: 1.02-1.62), 4.51-5.00 mmol/L (OR: 1.43, CI: 1.08-1.90) and above 5.00 mmol/L (OR: 1.74, CI: 1.21-2.51) had an increased risk of outcome when compared with potassium at 3.50-4.00 mmol/L. Sodium levels were inversely related to the risk of a composite outcome (<130 mmol/L: OR: 2.73 (95% CI, 1.81-4.12); 130-134 mmol/L: OR, 1.97 (CI, 1.45-2.68); 135-140 mmol/L: OR, 1.45 (CI, 1.17-1.81); p for trend < 0.001) in comparison with sodium at 141-145 mmol/L. Chloride < 95 mmol/L corresponded to a higher risk of a composite outcome with an OR of 1.65 (95% CI, 1.16-2.37) in contrast to chloride levels at 101-105 mmol/L. In addition, the adjusted ORs (95% CI) for a composite outcome comparing the STC < 2.00 and 2.00-2.24 vs. 2.25-2.58 mmol/L were 0.98 (0.69-1.43) and 1.13 (0.89-1.44), respectively. Besides that, the number of electrolyte abnormalities was positively related to the risk of a composite outcome (N = 1, OR 1.40, 95% CI: 1.13-1.73; N = 2, OR 2.51, 95% CI: 1.85-3.42; N = 3, OR 2.47, 95% CI: 1.45-4.19; p for trend < 0.001) in comparison with N = 0. CONCLUSIONS: A deviation of potassium levels from 3.50 to 4.00 mmol/L, lower sodium levels and hypochloremia were associated with poorer short-term prognosis of ADHF. Furthermore, the number of electrolyte abnormalities positively correlated with adverse short-term prognosis of patients with ADHF. Key MessagesADHF patients with baseline serum potassium at first half part of normal range (3.50-4.00 mmol/L) may herald the lowest risk of recent cardiovascular events.Serum sodium and chloride levels exhibit discrepancies in terms of risk of short-term adverse events of ADHF patients.The number of electrolyte abnormalities is a significant predictor of poor short-term prognosis in patients with ADHF. CLINICAL TRIAL REGISTRATION URL: http://www.chictr.org.cn/showproj.aspx?proj=23139. Unique identifier: ChiCTR-POC-17014020.

Serum Chloride Is Inversely Associated With 3 Months Outcomes in Chinese Patients With Heart Failure, a Retrospective Cohort Study.

Background: Serum chloride was recently found to be associated with prognosis of heart failure in western countries. However, the evidence was scarce in Asia. We aimed to investigated the relationship between serum chloride and clinical outcomes in a Chinese cohort with hospitalized heart failure. Methods: We retrospectively analyzed the data from PhysioNet, involving 1996 patients who were admitted with heart failure between December 2016 and June 2019. Outcome was a composite endpoint of all-cause death or rehospitalization at 3 months. Results: The incidence of the composite endpoint was 26.8% (535/1,996); it was 32.2% (213/662), 25.0% (165/661), and 23.3% (157/673) by chloride tertiles (from the lowest to the highest), respectively. The serum chloride at admission was independently and inversely associated with the composite endpoint risk (hazard ratio: 0.967; 95% confidence interval: 0.939 to 0.996; p = 0.026) in contrast to sodium, which was no longer significant (p > 0.05) after multivariable adjustment. Pearson correlation between serum chloride and sodium was 0.747 (p < 0.001). However, an increased AUC was not observed by adding sodium to model composed of age, sex, NYHA class, diabetes, log BNP and chloride (0.620 vs. 0.612, p = 0.132). Subgroup analysis showed the presence or absence of hyponatremia did not affect the association between chloride and composite endpoint risk. Conclusions: Low serum chloride at admission was associated with poor outcomes in Chinese hospitalized patients with heart failure. These findings warrant future studies for tackling the potential pathophysiological mechanisms and correction methods of hypochloremia in heart failure.

Prognostic significance of serum chloride level in heart failure patients with preserved ejection fraction.

AIMS: The prognostic value of serum chloride level has been reported primarily in patients with heart failure with reduced ejection fraction, and hence, there is limited evidence in patients of heart failure with preserved ejection fraction (HFpEF). This study was conducted to clarify the relationship between serum chloride level and clinical outcomes in patients with HFpEF with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Patient data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, a prospective multicentre observational registry for ADHF-HFpEF in Osaka. The data of 870 patients were analysed after excluding patients with in-hospital death, missing follow-up data, missing data of serum chloride level, or on chronic dialysis therapy. The primary endpoint of this study was all-cause mortality. At discharge, right ventricular systolic dysfunction was significantly associated with the lowest tertile of serum chloride level after multivariable adjustment (P = 0.0257). During a mean follow-up period of 1.8 ± 1.0 years, 186 patients died. Cox multivariable analysis showed that serum chloride level at discharge (P = 0.0017) was independently associated with all-cause mortality after multivariable adjustment of major confounders, whereas serum sodium level was no longer significant (P = 0.6761). Kaplan-Meier survival curve analysis revealed a significantly increased risk of mortality stratified by the tertile of serum chloride level [29% vs. 19% vs. 16%, P = 0.0002; hazard ratio (HR): 2.09 (95% confidence interval, CI: 1.31 to 3.34), HR: 1.03 (95% CI: 0.65 to 1.64)]. CONCLUSIONS: Serum chloride level was useful for the prediction of poor outcome in ADHF patients with preserved ejection fraction.

Association between serum chloride levels with mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Lower serum chloride (Cl) levels have been associated with excess mortality in pre-dialysis chronic kidney disease patients. However, the relationship between serum Cl levels and clinical outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 1656 eligible incident patients undergoing CAPD from 2006 to 2013, and followed until December 2018. Cox regression analyses were used to examine the association between baseline and time-varying serum Cl levels and mortality. During a median follow-up of 46 months, 503 patients (30.4%) died. In analyses of baseline serum Cl, the adjusted hazard ratios (HR) for tertile 1 (<100.0 mmol/L), tertile 2 (100.0-103.0 mmol/L) versus tertile 3 (>103.0 mmol/L) were 2.34 [95% confidence interval (CI) 1.43-3.82] and 1.73 (95% CI 1.24-2.42) for all-cause mortality, 2.86 (95% CI 1.47-5.56) and 1.90 (95% CI 1.19-3.02) for cardiovascular disease (CVD) mortality, respectively. And a linear relationship was observed between serum Cl and mortality. Further, the inverse association between serum Cl and CVD mortality was particularly accentuated in the patients who were ≥50 years or with a history of diabetes. Similarly, lower time-varying serum Cl levels were also associated with a significant increased risk of all-cause and CVD death. CONCLUSION: Lower serum Cl levels predicted higher risk of all-cause and CVD mortality in CAPD patients.

Increase in chloride from baseline is independently associated with mortality in intracerebral hemorrhage patients admitted to intensive care unit: A retrospective study.

Background: Hyperchloremia is associated with increased mortality in critically ill patients. The objective of this study was to investigate the association between increased chloride levels and mortality outcomes in intracerebral hemorrhage (ICH) patients admitted to the intensive care unit (ICU). Methods: We performed a retrospective study of all patients diagnosed with ICH and included in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ) from 2001 to 2012. Inclusion criteria were the first diagnosis of ICH, ICU length of stay (LOS) over 72 h, and not receiving hypertonic saline treatment. Serum chloride perturbation within 72 h of admission was evaluated as a predictor of outcomes. The increase in chloride from baseline was dichotomized based on an increase in chloride in 72 h (≤5 mmol/L or >5 mmol/L). The primary outcome was 90-day mortality. Results: A total of 376 patients (54.5% male, median age 70 years, interquartile range:58-79 years) were included. The overall 90-day mortality was 32.2% (n=121), in-hospital mortality was 25.8% (n=97), and Day 2 acute kidney injury (AKI) occurred in 29.0% (n=109) of patients. The prevalence of hyperchloremia on admission, during the first 72 h, and an increase in chloride (>5 mmol/L) were 8.8%, 39.4%, and 42.8%, respectively. After adjusting for confounders, the hazard ratio of increase in chloride (>5 mmol/L) was 1.66 (95% confidence interval:1.05-2.64, P=0.031). An increase in chloride (>5 mmol/L) was associated with a higher odds ratio for 90-day mortality in both the AKI and non-AKI groups. Conclusions: An increase in chloride from baseline is common in adult patients with ICH admitted to ICU. The increase is significantly associated with elevated mortality. These results support the significance of diligently monitoring chloride levels in these patients.

Is there any benefit with pantoprazole treatment in infantile hypertrophic pyloric stenosis?

CONTEXT: Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2 receptor antagonists. AIMS: We investigated if similar outcomes are achieved with IV pantoprazole, a proton-pump inhibitor (PPI), including the subgroup of delayed presenters in the South African setting. SETTINGS AND DESIGN: A 5-year retrospective record review (January 2014-December 2018) compared the rate of metabolic correction in patients with hypertrophic pyloric stenosis at two tertiary centres. SUBJECTS AND METHODS: One centre routinely administers IV pantoprazole (1 mg/kg daily) preoperatively (PPI group) and the other does not (non-PPI group). Fluid administration, chloride supplementation and post-operative emesis were evaluated. STATISTICAL ANALYSIS: Spearman's rank correlation coefficient was used to calculate statistical significance for discrete dependent variables. Continuous variables were compared between the groups using the Student t-test. Fisher's exact contingency tables were used to classify categorical data and to assess the significance of outcome between two treatment options. P < 0.05 was considered statistically significant. RESULTS: Forty-two patients received IV pantoprazole and 24 did not. The mean time of metabolic correction was 8 h shorter in the PPI group (P = 0.067). Total pre-operative chloride administration correlated to the rate of metabolic correction in both cohorts (P < 0.0001). Profound hypochloraemia (chloride <85 mmol/l) was corrected 23 h faster in the PPI group (P < 0.004). Post-operative emesis was noted: 0.45 episodes/patient in the PPI group and 0.75 episodes/patient in the non-PPI group (P = 0.01). CONCLUSIONS: Pre-operative IV pantoprazole administration showed a faster correction of metabolic derangements, and in profound hypochloraemia, the correction occurred substantially faster in the PPI group. Post-operative emesis was significantly less frequent in the PPI group.

Serum Chloride and Mortality in patients on continuous ambulatory peritoneal dialysis: A multi-center retrospective study.

BACKGROUND: Lower serum chloride is associated with a higher risk of mortality in the general population. However, the association has received little attention in peritoneal dialysis patients. The study aimed to examine the association between serum chloride and mortality in peritoneal dialysis patients. METHODS: In this multicenter retrospective cohort study, 2376 Chinese incident patients on peritoneal dialysis between January 1, 2005, and March 31, 2020, were included. Patients were grouped according to quartiles of serum chloride at baseline. The associations of baseline serum chloride and cardiovascular mortality and all-cause mortality were evaluated using cause-specific hazards models. FINDINGS: Of 2376 patients, the mean age was 45.9 (45.3,46.5) years, 50.1% of patients were men. The median serum chloride levels were 103.0 (99.0,106.9) mmol/L. During 9304.5 person-years of follow-up, 462 patients died, of which 235 deaths were caused by cardiovascular disease. The highest quartile group was associated with a higher risk of cardiovascular mortality (adjusted hazards ratio [HR], 2.95; 95% confidence interval [CI], 1.80 to 4.95) and all-cause mortality (adjusted HR, 2.03; 95% CI, 1.45 to 2.83) compared with the lowest quartile. The similar trend was also found when serum chloride levels were deal as continuous variable. INTERPRETATION: Higher serum chloride at the initial of peritoneal dialysis was associated with a higher risk of cardiovascular mortality and all-cause mortality in patients on peritoneal dialysis. FUNDING: This work was supported by Shanghai Municipal Health Commission (2019SY018).

Serum Chloride Level Is Associated With Abdominal Aortic Calcification.

BACKGROUND: Abdominal aortic calcification is a potentially important independent risk factor for cardiovascular health. The aim of this study was to determine the relationship between serum chloride level and abdominal artery calcification. METHODS: We obtained the data of 3,018 individuals from the National Health and Nutrition Examination Survey database and analyzed the relationship between serum chloride and abdominal artery calcification. We performed stratified and single factor analysis, multiple equation regression analysis, smooth curve fitting, and threshold effect and saturation effect analysis. R and EmpowerStats were used for data analysis. RESULTS: Serum chloride is independently related to the AAC total 24 score (AAC-24). The smooth curves fitted were all inverted-U shaped. Below a cutoff value of 92 mmol/L, increase in serum chloride level was associated with increase in AAC-24; however, above that cutoff, increase in serum chloride level was associated with decrease in AAC-24. CONCLUSIONS: At serum levels below 92 mmol/L, chloride is a risk factor for abdominal aortic calcification but levels above 92 mmol/L appear to protect against abdominal aortic calcification.

Ion chromatography as candidate reference method for the determination of chloride in human serum.

BACKGROUND: We developed an ion chromatography (IC) method for measurement of chloride in human serum which was regarded as a simple, rapid, accurate, and sensitive technique. The method will be hopefully selected as a candidate reference method. METHOD: Serum aliquots of 0.1 mL were diluted 500 times with Milli-Q water, and chloride in serum samples was measured by IC with a gradient elution procedure using a KOH eluent generator. RESULTS: Based on the data, chloride in human serum was well detected by IC. The calibration curve for chloride was linear in the concentration range from 0 to 0.42 mmol/L with a correlation coefficient of .99995 under the optimum experimental conditions. The chloride concentration had a good linear relationship with the peak areas of chloride. This method was sensitive because of the low limit of detection (LOD) and the low limit of quantification (LOQ) 9.87 × 10-5  mmol/L and 3.27 × 10-4  mmol/L, respectively. Besides, the method was highly precise with the within-run coefficient of variations (CVs) for the measurement of low, medium, and high concentration level samples 0.32%, 0.73%, and 0.50%. As for the evaluation of accuracy, the biases were less than ±1% and 2% by comparing with National Institute of Science and Technology (NIST) standard material SRM 956d and 2013-2018 IFCC-RELA samples, respectively. Finally, the biases between IC method and the inductively coupled plasma mass spectrometry (ICP-MS) method were less than 1% which showed good agreement. CONCLUSION: Ion chromatography is a simple sample treatment procedure for the determination of chloride in human serum with high sensitivity and specificity. The proposed method could be recommended as a candidate reference method for the determination of serum chloride in human serum.