Prognostic value of hypochloremia on mortality in patients with heart failure: a systematic review and meta-analysis.

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.

Electrolyte disturbances in patients hospitalized for COVID-19 infection: An observational study.

There are multiple mechanisms by which The Coronavirus-19 (COVID-19) infection can cause electrolyte abnormalities, which may not be the case for bacterial causes of pneumonia. This study aimed to assess the differences in electrolyte levels between patients suffering from COVID-19 and bacterial pneumonia. This is an original, retrospective study. Two cohorts of hospitalized patients were included, 1 suffering from COVID-19 and the other from bacterial pneumonia. Their day 1 and day 3 levels of sodium, potassium, magnesium, and phosphorus, as well as their outcomes, were extracted from the charts. Statistical analysis was subsequently performed. Mean admission levels of sodium, potassium, phosphorus, and magnesium were 135.64 ±â€…6.13, 4.38 ±â€…0.69, 3.53 ±â€…0.69, and 2.03 ±â€…0.51, respectively. The mean day 3 levels of these electrolytes were 138.3 ±â€…5.06, 4.18 ±â€…0.59, 3.578 ±â€…0.59, and 2.11 ±â€…0.64, respectively. Patients suffering from bacterial pneumonia were significantly older (N = 219, mean = 64.88 ±â€…15.99) than patients with COVID-19 pneumonia (N = 240, mean = 57.63 ±â€…17.87). Bacterial pneumonia group had significantly higher serum potassium (N = 211, mean = 4.51 ±â€…0.76), and magnesium (N = 115, mean = 2.12 ±â€…0.60) levels compared to COVID-19 group (N = 227, mean = 4.254 ±â€…0.60 for potassium and N = 118, mean = 1.933 ±â€…0.38 for magnesium). Only magnesium was significantly higher among day 3 electrolytes in the bacterial pneumonia group. No significant association between electrolyte levels and outcomes was seen. We found that COVID-19 patients had lower potassium and magnesium levels on admission, possibly due to the effect of COVID-19 on the renin-angiotensin-aldosterone system as well as patient characteristics and management. We did not find enough evidence to recommend using electrolyte levels as a determinator of prognosis, but more research is needed.

Development and validation of potential phenotypes of serum electrolyte disturbances in critically ill patients and a Web-based application.

BACKGROUND: Electrolyte disturbances are highly heterogeneous and severely affect the prognosis of critically ill patients. Our study was to determine whether data-driven phenotypes of seven electrolytes have prognostic relevance in critically ill patients. METHODS: We extracted patient information from three large independent public databases, and clustered the electrolyte distribution of ICU patients based on the extreme value, median value and coefficient of variation of electrolytes. Three plausible clinical phenotypes were calculated using K-means clustering algorithm as the basic clustering method. MIMIC-IV was considered a training set, and two others have been designated as verification set. The robustness of the model was then validated from different angles, providing dynamic and interactive visual charts for more detailed characterization of phenotypes. RESULTS: 15,340, 12,445 and 2147 ICU patients with electrolyte records during early ICU stay in MIMIC-IV, eICU-CRD and AmsterdamUMCdb were enrolled. After clustering, three reasonable and interpretable phenotypes are defined as α, ß and γ according to the order of clusters. The α and γ phenotype, with significant differences in electrolyte distribution and clinical variables, higher 28-day mortality and longer length of ICU stay (p < 0.001), was further demonstrated by robustness analysis. The α phenotype has significant kidney injury, while the ß phenotype has the best prognosis. In addition, the assignment methods of the three phenotypes were developed into a web-based tool for further verification and application. CONCLUSIONS: Three different clinical phenotypes were identified that correlated with electrolyte distribution and clinical outcomes. Further validation and characterization of these phenotypes is warranted.

Fluid status in the first 10 days of life and death/bronchopulmonary dysplasia among preterm infants.

OBJECTIVE: To investigate the association between fluid and sodium status in the first 10 postnatal days and death/bronchopulmonary dysplasia (BPD) among infants born <29 weeks' gestation. STUDY DESIGN: Single center retrospective cohort study (2015-2018) of infants born 23-28 weeks'. Three exposure variables were evaluated over the first 10 postnatal days: cumulative fluid balance (CFB), median serum sodium concentration, and maximum percentage weight loss. Primary outcome was death and/or BPD. Multivariable logistic regression adjusting for patient covariates was used to assess the association between exposure variables and outcomes. RESULTS: Of 191 infants included, 98 (51%) had death/BPD. Only CFB differed significantly between BPD-free survivors and infants with death/BPD: 4.71 dL/kg (IQR 4.10-5.12) vs 5.11 dL/kg (IQR 4.47-6.07; p < 0.001). In adjusted analyses, we found an association between higher CFB and higher odds of death/BPD (AOR 1.56, 95% CI 1.11-2.25). This was mainly due to the association of CFB with BPD (AOR 1.60, 95% CI 1.12-2.35), rather than with death (AOR 1.08, 95% CI 0.54-2.30). CONCLUSION: Among preterm infants, a higher CFB in the first 10 days after delivery is associated with higher odds of death/BPD. IMPACT: Previous studies suggest that postnatal fluid status influences survival and respiratory function in neonates. Fluid balance, serum sodium concentration, and daily weight changes are commonly used as fluid status indicators in neonates. We found that higher cumulative fluid balance in the first 10 days of life was associated with higher odds of death/bronchopulmonary dysplasia in neonates born <29 weeks. Monitoring of postnatal fluid balance may be an appropriate non-invasive strategy to favor survival without bronchopulmonary dysplasia. We developed a cumulative fluid balance chart with corresponding thresholds on each day to help design future trials and guide clinicians in fluid management.

Identification of a Novel Natriuretic Protein in Patients With Cerebral-Renal Salt Wasting-Implications for Enhanced Diagnosis.

BACKGROUND: The most vexing problem in hyponatremic conditions is to differentiate the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from cerebral/renal salt wasting (C-RSW). Both have identical clinical parameters but diametrically opposite therapeutic goals of water- restricting water-logged patients with SIADH or administering salt and water to dehydrated patients with C-RSW. While C-RSW is considered a rare condition, the report of a high prevalence of C-RSW in the general hospital wards creates an urgency to differentiate one syndrome from the other on first encounter. We decided to identify the natriuretic factor (NF) we previously demonstrated in plasma of neurosurgical and Alzheimer diseases (AD) who had findings consistent with C-RSW. METHODS: We performed the same rat renal clearance studies to determine natriuretic activity (NA) in serum from a patient with a subarachnoid hemorrhage (SAH) and another with AD and demonstrated NA in their sera. The sera were subjected to proteomic and SWATH (Sequential Windowed Acquisition of All) analyses which identified increased levels of haptoglobin related protein (Hpr) without signal peptide (Hpr-WSP). RESULTS: Recombinant Hpr with His tag at the N terminus had no NA. Hpr-WSP had a robust NA in a dose-dependent manner when injected into rats. Serum after recovery from C-RSW in the SAH patient had no NA. CONCLUSIONS: Hpr-WSP may be the NF in C-RSW which should be developed as a biomarker to differentiate C-RSW from SIADH on first encounter, introduces a new syndrome of C-RSW in AD and can serve as a proximal diuretic to treat congestive heart failure.

New onset adrenal insufficiency in a patient with COVID-19.

SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.

Vascular endothelial growth factor D is a biomarker of fluid overload in haemodialysis patients.

BACKGROUND: Improved understanding and assessment of the complex physiology of volume regulation in haemodialysis (HD) patients are required to improve patient care and reduce mortality associated with fluid overload (FO). METHODS: We searched for FO-related biomarkers among 184 peptides associated with cardiovascular disease in a cohort of 30 HD patients. First, we assessed the direct impact of HD on the peptides of interest by comparing plasma concentrations before and after treatment. Then, we compared cardiovascular peptide profiles between patients with and without FO as defined by bioimpedance analysis (BIA). The plasma concentration of selected candidate biomarkers for FO was determined by enzyme-linked immunosorbent assay (ELISA) and correlated with previously described FO-related clinical and laboratory parameters. For validation, results were confirmed in an independent cohort of 144 HD patients. RESULTS: We found seven peptides positively [NT-proBNP, B-type natriuretic peptide (BNP), vascular endothelial growth factor D (VEGFD), tumour necrosis factor-related apoptosis-inducing ligand receptor 2, growth differentiation factor 15, tumour necrosis factor ligand superfamily member 13B, chitinase-3-like protein 1] and five negatively (leptin, renin, epidermal growth factor receptor, interleukin-1 receptor antagonist, myeloblastin) correlated to FO. In addition to natriuretic peptides, VEGFD emerged as third peptide highly correlated with BIA (ρ = 0.619, P < 0.0001). In line with this, VEGFD concentration verified by ELISA correlated with BIA, BNP and soluble CD146 but not with vascular endothelial growth factor C (VEGFC). Notably, levels of VEGFD were unrelated to cardiac systolic function (P = 0.63), contrary to BNP (P = 0.0003). Finally, we observed that 1-year all-cause mortality was higher in patients with high BNP (P = 0.0002), FO (defined by BIA, P = 0.04) and high VEGFD (P = 0.02), but not with high VEGFC (P = 0.48). CONCLUSION: VEGFD is a novel FO-related biomarker with unique diagnostic and prognostic properties.

Modulation of the Association of Hypobicarbonatemia and Incident Kidney Failure With Replacement Therapy by Venous pH: A Cohort Study.

RATIONALE & OBJECTIVE: Studies showing an association between lower bicarbonate levels and worse kidney disease prognosis have not accounted for the influence of pH. It remains unknown whether this association is consistent across a wide range of blood pH values. This study sought to assess how pH modifies the relationship between hypobicarbonatemia and incident kidney failure requiring kidney replacement therapy (KFRT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,058 Japanese patients with estimated glomerular filtration rates<60mL/min/1.73m2. EXPOSURE: Baseline venous bicarbonate levels and venous pH. OUTCOME: KFRT defined as initiation of kidney replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation). ANALYTICAL APPROACH: Cox proportional hazards model assessing the interaction between baseline bicarbonate levels and venous pH on incident KFRT. RESULTS: In the lowest bicarbonate quartile (≤21.5 mEq/L), 59% of patients had acidemia (pH<7.32), whereas 38% had venous pH within the normal range and 3% had alkalemia (pH>7.42). During a median follow-up of 3.0 years, 374 patients developed KFRT. Venous pH modified the association between bicarbonate level and rate of KFRT (P for interaction=0.04). After adjustment for potential confounders, including capacity for respiratory compensation, the lowest (vs the highest) bicarbonate quartile was associated with a 2.29-fold (95% CI, 1.10-4.77; P=0.03) higher rate of KFRT among patients with acidemia (pH<7.32). In contrast, among patients without acidemia (pH≥7.32), no significant association was found between bicarbonate level and KFRT. In an exploratory analysis, patients with higher respiratory compensation capacity had a lower rate of KFRT (HR per 0.1 increase in respiratory compensation capacity, 0.90; 95% CI, 0.87-0.94; P<0.001). LIMITATIONS: Observational study design; blood gas measurements were performed in a select patient population. CONCLUSIONS: Venous pH modified the association of hypobicarbonatemia with progression of chronic kidney disease to KFRT. Measurement of venous pH may be valuable for identifying patients with chronic kidney disease and hypobicarbonatemia and may inform treatment.

Assessment of Hydration Status in Peritoneal Dialysis Patients: Validity, Prognostic Value, Strengths, and Limitations of Available Techniques.

BACKGROUND: The majority of patients undergoing peritoneal dialysis (PD) suffer from volume overload and this overhydration is associated with increased mortality. Thus, optimal assessment of volume status in PD is an issue of paramount importance. Patient symptoms and physical signs are often unreliable indexes of true hydration status. SUMMARY: Over the past decades, a quest for a valid, reproducible, and easily applicable technique to assess hydration status is taking place. Among existing techniques, inferior vena cava diameter measurements with echocardiography and natriuretic peptides such as brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide were not extensively examined in PD populations; while having certain advantages, their interpretation are complicated by the underlying cardiac status and are not widely available. Bioelectrical impedance analysis (BIA) techniques are the most studied tool assessing volume overload in PD. Volume overload assessed with BIA has been associated with technique failure and increased mortality in observational studies, but the results of randomized trials on the value of BIA-based strategies to improve volume-related outcomes are contradictory. Lung ultrasound (US) is a recent technique with the ability to identify volume excess in the critical lung area. Preliminary evidence in PD showed that B-lines from lung US correlate with echocardiographic parameters but not with BIA measurements. This review presents the methods currently used to assess fluid status in PD patients and discusses existing data on their validity, applicability, limitations, and associations with intermediate and hard outcomes in this population. Key Message: No method has proved its value as an intervening tool affecting cardiovascular events, technique, and overall survival in PD patients. As BIA and lung US estimate fluid overload in different compartments of the body, they can be complementary tools for volume status assessment.

Clinical effect and safety of continuous renal replacement therapy in the treatment of neonatal sepsis-related acute kidney injury.

BACKGROUND: Sepsis is the leading cause of acute kidney injury (AKI) in the neonatal intensive care unit (NICU). The aim of the study is to explore the efficacy and security of continuous renal replacement therapy (CRRT) in the treatment of neonatal sepsis-related AKI. METHOD: Totally12 sepsis-related AKI neonates treated with CRRT were hospitalized in the NICU of Shanghai Children's Hospital between November 2012 and November 2019, and the clinical data of these 12 cases were retrospectively analyzed. Renal function, acid-base balance, electrolytes, blood pressure and hemodynamics indexes were recorded before CRRT initiation, 12/24/48 h after CRRT initiation and at the end of CRRT respectively. The efficacy of CRRT was evaluated and the clinical outcome was observed in these 12 sepsis-related AKI neonates. Repeated measurement analysis of variance was used for statistical analysis of the data. RESULT: (1) Continuous veno-venous hemodialysis filtration (CVVHDF) was used in 12 cases of sepsis-related AKI neonates. There were 6 cases with oliguria, 3 cases with fluid overload (FO), 3 cases with septic shock. The duration of CRRT was 49 ~ 110 h, average (76.2 ± 23.5) h. (2) The blood pressure (BP) of 12 sepsis -related AKI neonates could reach the normal level (40-60 mmHg) 12 h after CRRT initiation, and the normal BP level could be maintained during the CRRT treatment. After 12 h CRRT, the blood pH value increased to the normal range (7.35 ~ 7.45). After 12 h CRRT treatment, the oxygenation index of 12sepsis-related AKI neonates could reach 200 mmHg. After 24 h CRRT treatment, it could rise to more than 300 mmHg. Serum potassium, serum urea nitrogen and serum creatinine levels decreased significantly 12 h after CRRT initiation, and reached the normal range 24 h after CRRT initiation. The urine volume significantly increased 24 h after CRRT initiation. (3) Venous catheterization was performed successfully in all sepsis-related AKI neonates. We observed 2 cases of thrombocytopenia, 1 case of obstruction and 1 case of hypotension in the course of CRRT. There were no complications such as hypothermia, hemorrhage, thrombosis and infection.11 neonates were cured and discharged. One neonate was treated with CRRT and passed through the oliguria stage of AKI, but died after the parents gave up the treatment. CONCLUSIONS: It is safe and effective to treat neonatal sepsis-related AKI with CRRT, which should be an effective measure for the treatment of sepsis-related AKI neonates.

Association of predialysis serum sodium level with fluid status in patients on maintenance hemodialysis.

PURPOSE: The ability to maintain sodium and water homeostasis is impaired in patients with end-stage renal disease (ESRD), leading to hyponatremia and fluid overload. The aim of this study was to evaluate the association between serum sodium level and body fluid status in patients on maintenance hemodialysis (HD). METHODS: This was a prospective observational study on patients with ESRD and who were on maintenance HD between June and November 2018. Assessment of body fluid status using bioimpedance spectroscopy and measurement of serum sodium level were conducted simultaneously predialysis. The association of fluid status with predialysis sodium level was analyzed. RESULTS: Sixty-two patients were enrolled in the study group. Compared with patients with predialysis normonatremia, those with predialysis hyponatremia had higher levels of blood urea nitrogen, serum potassium, phosphate, normalized protein catabolic rate, and interdialytic weight gain (IDWG) (p < 0.05). The correlations of predialysis sodium level with chronic fluid status, such as fluid overload, were not significant. Logistic regression analysis found significant association of IDWG with predialysis hyponatremia. CONCLUSION: Predialysis hyponatremia was associated with increased IDWG. The substantial variation in serum sodium levels, regardless of fluid status, indicated the complex relationship between sodium and water balance in patients on maintenance HD.

Electrolyte Abnormalities in Patients Presenting With Ventricular Arrhythmia (from the LYTE-VT Study).

Electrolyte abnormalities are a known trigger for ventricular arrhythmia, and patients with heart disease on diuretic therapy may be at higher risk for electrolyte depletion. Our aim was to determine the prevalence of electrolyte depletion in patients presenting to the hospital with sustained ventricular tachycardia or ventricular fibrillation (VT/VF) versus heart failure, and identify risk factors for electrolyte depletion. Consecutive admissions to a tertiary care hospital for VT/VF were identified between July 2016 and October 2018 using the electronic medical record and compared with an equal number of consecutive admissions for heart failure (CHF). The study included 280 patients (140 patients in each group; mean age 63, 60% male, 59% African American). Average EF in the VT/VF and CHF groups was 30% and 33%, respectively. Hypokalemia (K < 3.5 mmol/L) and severe hypokalemia (K < 3.0 mmol/L) were present in 35.7% and 13.6%, respectively, of patients with VT/VF, compared to 12.9% and 2.7% of patients with CHF (p < 0.001 and p = 0.001, respectively, between groups). Hypomagnesemia was found in 7.8% and 5.8% of VT/VF and CHF patients, respectively (p = 0.46). Gastrointestinal illness and recent increases in diuretic dose were strongly associated with severe hypokalemia in VT/VF patients (odds ratio: 11.1 and 21.9, respectively; p < 0.001). In conclusion, hypokalemia is extremely common in patients presenting with VT/VF, much more so than in patients with CHF alone. Preceding gastrointestinal illness and increase in diuretic dose were strongly associated with severe hypokalemia in the VT/VF population, revealing a potential opportunity for early intervention and arrhythmia risk reduction.

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

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

B-type natriuretic peptide levels and diagnostic accuracy: excess fluid volume.

AIM: To analyze the behavior of B-type natriuretic peptide (BNP) in the presence of defining characteristics (DCs) of the nursing diagnosis Excess fluid volume (00026) in patients hospitalized for acute decompensated heart failure. METHODS: Cohort study of patients admitted with acute decompensated heart failure (September 2015 to September 2016) defined by Boston Criteria. Patients hospitalized for up to 36 h with BNP values ≥ 100 pg/ml were included; BNP values at baseline-final assessment were compared by Wilcoxon test, the number of DCs at baseline-final assessment was compared by paired t-test. RESULTS: Sixty-four patients were included; there was a significant positive correlation between delta of BNP and the number of DCs present at initial clinical assessment. CONCLUSIONS: The behavior of BNP was correlated to the DCs indicating congestion. With clinical compensation, DCs and BNP decreased. The use of this biomarker may provide additional precision to the nursing assessment.

Acute Bromide Intoxication in a Patient with Preserved Renal Function.

BACKGROUND Electrolyte imbalance is frequent in many situations, but severe hyperchloremia is markedly rare in the absence of renal impairment. We report a patient with preserved renal function who exhibited severe hyperchloremia and negative anion gap. CASE REPORT A 70-year-old female with preserved renal function presented with fatigue and impaired consciousness. Venous blood gas analysis was notable for a chloride level of 137 mEq/L and anion gap of -18.2 mEq/L. Careful history taking revealed that she had taken bromide-containing over-the-counter painkillers. Her symptoms and laboratory tests gradually improved after intravenous hydration and painkiller withdrawal. The serum level of bromide ions on admission was later found to be 4-times higher than that considered toxic. CONCLUSIONS It is important to recognize that hyperchloremia with a negative anion gap strongly suggests bromide intoxication, and that bromide intoxication can develop even in patients with preserved renal function. Careful history taking is essential to the diagnosis because some over-the-counter drugs that are widely available and a few prescription drugs contain bromides.

The dynamic relationship between serum chloride and cardiorenal syndrome.

Low serum sodium concentration has long been recognized as an established marker of short- and long-term morbidity and mortality in patients with heart failure (HF), and is commonly included in various risk prediction models. Mechanisms leading to hyponatremia (e.g. maladaptive neurohormonal activation) could also lead to concurrent decline in serum chloride levels. Besides, chloride has distinct biological roles (e.g. modulation of renal tubular sodium transporters) that are relevant to the pathophysiology and therapy of HF, making it a potent cardiorenal connector. Several clinical studies have recently reported on a potentially overlooked link between low serum chloride levels and adverse outcomes in patients with a wide variety of HF syndromes, which could indeed be stronger than that of sodium. While evidence on predictive value of chloride is accumulating in various patient populations and settings, the limited available interventional studies have so far yielded conflicting results. It remains to be elucidated whether hypochloremia represents a marker of disease severity and prognosis, or it is an actual pathogenetic mechanism, hence being a potential novel target of therapy. Current ongoing studies are designed to better understand the mechanistic aspects of the role of hypochloremia in HF and shed light on its clinical applicability.

Effects of hyperchloremia on renal recovery in critically ill children with acute kidney injury.

BACKGROUND: Serum chloride derangements are associated with poor clinical outcomes, including acute kidney injury (AKI) and mortality. We sought to determine the association between persistent hyperchloremia and renal recovery in critically ill children with AKI. METHODS: We performed a retrospective cohort study of all patients with day 2 AKI admitted to a large academic pediatric intensive care unit from January 2014 to December 2015. After applying exclusion criteria, 348 patients were categorized as (1) hyperchloremia on both day 2 and day 7 (PersistentCl), (2) hyperchloremia on day 2 with normochloremia on day 7 (RecoveredCl), (3) normochloremia on day 2 with hyperchloremia on day 7 (DelayedCl), and (4) no hyperchloremia on day 2 nor day 7 (NormalCl). Hyperchloremia was defined as ≥ 110 mEq/L. The primary outcome was renal recovery on day 7, defined as the absence of AKI criteria. Secondary outcomes included discharge renal recovery, mortality, duration of mechanical ventilation, and hospital length of stay. RESULTS: Day 7 renal recovery rates for PersistentCl, RecoveredCl, DelayedCl, and NormalCl were 37%, 66%, 71%, and 52% respectively. PersistentCl had lower odds of day 7 renal recovery (aOR = 0.29; 95% CI, 0.14 to 0.60; p = 0.0009), lower odds of discharge renal recovery (aOR = 0.22; 95% CI, 0.11 to 0.48; p = 0.0001), and higher odds of mortality (aOR = 3.50; 95% CI, 1.11 to 11.10; p = 0.03) when compared with RecoveredCl after adjusting for confounders. CONCLUSIONS: Persistent hyperchloremia is independently associated with impaired renal recovery as well as higher mortality. Prospective studies are indicated to determine if serum chloride represents a modifiable risk factor for poor outcomes. Graphical abstract.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.