Anion Gap Research Articles

A-092 Siemens Healthineers Commitment to Quality - A Focus on Continuous Improvement and Customer Experience

Abstract Background It is necessary that each step of in vitro diagnostic assay development and manufacturing processes be documented and executed in alignment with established quality management systems. Here, we describe how Siemens Healthineers (SHS) maintains assay traceability and focus on continuous improvement using the Atellica® CH A-LYTE® Integrated Multisensor Technology (IMT) assays measuring electrolytes sodium (Na), potassium (K), and chloride (Cl) as a prime example. Methods Establishing an unbroken chain of comparison from the National Institute of Standards and Technology (NIST) higher standard references to the product calibrators ensures accurate value assignment within stated measurement uncertainties. Traceability and standardization are achieved by creating a panel of 10 serum anchor pools spanning the analytical measuring interval for each electrolyte: Na, K, and Cl. The concentrations of the anchor pools are determined at a reference laboratory using methods calibrated with standard solutions derived from NIST reference material. These serum anchor pools are used by SHS, assigning values to product calibrator material which maintains the chain of traceability to the primary reference methods. In addition to traceability, onboard stability for the A-LYTE® IMT multisensor is continuously monitored and evaluated against allowable drift limits for each electrolyte. Although observed drift was within allowable limits, a design change was implemented to improve recovery drift over the use life of the sensor. Results To ensure consistent, robust, and accurate performance of the A-LYTE IMT, a strict set of testing procedures are used to verify the accuracy of value assignments for each manufactured lot of master standards. The recovery of the NIST standard reference material must fall within manufacturer established acceptable bias limits. Consistency over nine master lots is shown with bias ranging from -0.9% to +1.9%, -2.4% to +1.8% and -1.8 to +0.5%, for Na, K and Cl, respectively. By further optimizing the amount of Na ionophore and the polymer matrix of the Na sensor, drift over the use life was minimized and onboard stability improved. Prior to making the sensor change, customer Na QC data at 116 mmol/L showed an SD of 1.1 mmol/L (n=585), whereas the precision improved to an SD of 0.6 mmol/L (n=470) post-optimization. As Manufacturers optimize assay performance, it may become necessary for laboratories to re-evaluate reference intervals for their patient populations. For example, one large integrated delivery network established a new reference interval for patient anion gap (AG). A re-evaluation of the historical AG reference interval which was 5-15 mmol/L identified the need for an update. AG values were calculated from 16,948 healthy patients and used to establish a new reference interval of 2-10 mmol/L. Conclusions Accurate clinical laboratory measurements are critical for diagnosing, monitoring, and treating diseases. A-LYTE assays have an unbroken chain of traceability to NIST reference material and minimal drift over the life of the multisensor. Continuous monitoring to identify improvement projects and rigorous control systems ensure sensor performance over time. This provides confidence that the patient results produced by the laboratory are accurate and consistent over time and across different laboratory locations.

Elevated osmol gaps in patients with alcoholic ketoacidosis.

The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 27. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

Hyperchloremic metabolic acidosis potentially benefiting sodium bicarbonate therapy: A multi-center cohort study

BackgroundThe use of sodium bicarbonate for metabolic acidosis has been a topic of debate, primarily due to the lack of clinical efficacy evidence. This study aims to identify which types of patients with various acid-base balance parameters can benefit from sodium bicarbonate therapy. MethodsPatients diagnosed with metabolic acidosis were screened from a large multi-center critical care database to form a retrospective cohort. Mortality curves, logistic regression analysis, simulation methods, and propensity scores were used to compare data between sodium bicarbonate (SOB group) and non-treated (Non-SOB group) patients. ResultsThere was an interaction between baseline chloride, anion gap levels and sodium bicarbonate therapy on patients' in-hospital death. As chloride levels increased, the in-hospital mortality curves of the SOB group and Non-SOB group gradually converged, with the difference narrowing from approximately 20 % to 10 %, and then gradually widened with the increase of the anion gap. Furthermore, when patients had high chloride levels (≥112 mmol/L), those in the SOB group exhibited a higher incidence of hypernatremia, hypokalemia, and hypocalcemia at 24 h, and a lower incidence of hyperchloremia. Patients in SOB group also had a lower simulated mortality. Among patients treated with sodium bicarbonate, those with low chloride had more difficulty in normalizing pH compared to those with high chloride. ConclusionsThis study identified an interaction between baseline chloride and sodium bicarbonate therapy on patient survival. Hyperchloremic metabolic acidosis may potentially benefit from sodium bicarbonate therapy. Further prospective randomized controlled studies are warranted.

Treatment of 5-oxyproline Anion Gap Acidosis with N-acetylcysteine

Treatment of 5-oxyproline Anion Gap Acidosis with N-acetylcysteine

Revisiting the Urinary Anion Gap: A Sound Concept during Hyperchloremic Metabolic Acidosis

Revisiting the Urinary Anion Gap: A Sound Concept during Hyperchloremic Metabolic Acidosis

Relationship between the albumin-corrected anion gap and short-term prognosis among patients with cardiogenic shock: a retrospective analysis of the MIMIC-IV and eICU databases

ObjectivesWe aimed to investigate the association between the albumin-corrected anion gap (ACAG) and the prognosis of cardiogenic shock (CS).DesignA multicentre retrospective cohort study.SettingData were collected from the Medical Information Mart...

A side effect that should be considered in patients using metformin: lactic acidosis

The most serious and life-threatening side effect seen in patients using metformin is metabolic acidosis. If there is a history of diabetes in patients with high anion gap metabolic acidosis who present to the emergency department, metformin use should be questioned. In our case, metformin-related lactic acidosis was detected in a 67-year-old female patient who applied to the emergency department with a complaint of palpitations. The patient's kidney function tests were within normal range and he did not describe excessive drug intake. Despite the treatments administered in the emergency room, the patient's blood gas lactate level continued to increase and his acidosis deepened. After other causes of lactic acidosis were excluded, the patient was consulted with internal medicine and transferred to the intensive care unit. With this case report, we tried to draw attention to the fact that the patient group for which metformin will be used in the treatment should be carefully selected and that lactic acidosis, which is a fatal side effect, should be considered in the differential diagnosis and treatment should be started in those using this drug.

Classic ketogenic diet-induced ketoacidosis in the treatment of pyruvate dehydrogenase deficiency: a case report and literature review

BackgroundAs a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD.Case presentationHerein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient.ConclusionsThis rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

Drug-Related Pyroglutamic Acidosis: Systematic Literature Review.

Background: Inborn errors of glutathione metabolism may cause high anion gap metabolic acidosis due to pyroglutamic acid accumulation. Since 1988, cases of this acidosis have been reported in individuals without these defects. Methods: Given the poorly characterized predisposing factors, presentation, management, and prognosis of acquired pyroglutamic acidosis, we conducted a systematic review using the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar databases. Results: A total of 131 cases were found. Most patients were females (79%), adults (92%) aged 51 years or older (66%) with pre-existing conditions (74%) such as undernutrition, alcohol-use disorder, or kidney disease, and had an ongoing infection (69%). The clinical features included diminished consciousness (60%), Kussmaul breathing (56%), and nausea or vomiting (27%). At least 92% of patients were on paracetamol therapy for >10 days at an appropriate dose, 32% on a β-lactamase-resistant penicillin, and 2.3% on vigabatrin. Besides severe anion gap acidosis, patients also presented with hypokalemia (24%) and kidney function deterioration (41%). Management involved discontinuing the offending drug (100%), bicarbonate (63%), acetylcysteine (42%), and acute kidney replacement therapy (18%). The fatality rate was 18%, which was higher without acetylcysteine (24%) compared to with it (11%). Conclusions: Acquired pyroglutamic acidosis is a rare, potentially fatal metabolic derangement, which usually occurs after paracetamol use, frequently combined with a β-lactamase-resistant penicillin or vigabatrin. This condition predominantly affects adults, especially women with factors like undernutrition, alcohol-use disorder, or kidney disease, often during infection. Increased awareness of this rare condition is necessary.

Increased serum albumin corrected anion gap levels are associated with poor prognosis in septic patients with liver cirrhosis

The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258–2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan–Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.

Insights into the baseline blood pH homeostasis at admission and the risk of in-hospital mortality in COVID-19 patients.

Aim: A laboratory finding in critically ill COVID-19 patients is blood academia (pH <7.35). We investigated its cause in connection with the admission baseline blood pH homeostasis.Patients & methods: We retrospectively monitored the baseline blood pH homeostasis of 1215 COVID-19 patients who were admitted with pneumonia using data-driven knowledge. Two categories of patients were identified: non-survivors (107) and survivors (1108).Results: Non-survivors showed greater levels of lactate and lower blood pH, saturation, and partial pressure of oxygen than survivors. A bivariate Spearman's correlation matrix showed that the [HCO3-]/pCO2 and pCO2 of non-survivors exhibited an unmatched connection, but not in the survivor group. When comparing non-survivors to survivors, the dendrograms derived from the bivariate comparison matrix showed differences in gasometry parameters like blood pH, [HCO3-]/pCO2 ratio, anion gap and pO2.Conclusion: The little variations in the gasometry readings between survivors and non-survivors upon admission suggested abnormal changes in the complementary renal and respiratory systems that bring blood pH back to normal. In advanced COVID-19, modest blood acid-base imbalances could become blood acidemia if these compensatory strategies were overused. Data-driven monitoring of acid-base parameters may help predict abnormal blood pH and the advancement of metabolic acidemia before it is too late.

Early Versus Late Administration of Long-Acting Insulin in Adult Diabetic Ketoacidosis.

Evidence is inconclusive if early administration of subcutaneous (SQ) long-acting insulin (LAI) in management of diabetic ketoacidosis (DKA) improves outcomes. This study compares early versus late administration of SQ LAI in time to DKA resolution. This single-center, retrospective study included patients with DKA who received ≥12 hours of continuous intravenous insulin (CIVI) with LAI overlap. Patients were compared based on LAI administration time to CIVI initiation: Early (<12 hours) versus Late (≥12 hours). The DKA resolution is defined as blood glucose < 200 mg/dL and 2 of the following: anion gap < 12 mEq/L, pH > 7.35, or serum carbon dioxide >15 mEq/L. Outcomes included time to DKA resolution, length of stay (LOS), CIVI duration, and adverse events. A total of 27 patients were included in each group. Baseline characteristics were similar between both groups. There was no difference in time to DKA resolution, Early = 17.6 (13.9-26.8) hours versus Late = 19.2 (17.1-32.1) hours, P = 0.16. The Early group had shorter CIVI duration (Early = 19.5 ± 10.3 hours vs Late = 25.6 ± 8.4 hours, P = 0.02) and received less intravenous (IV) fluids in the first 36 hours (Early = 4.04 ± 2.12 L vs Late = 5.85 ± 2.24 L, P = 0.004). No differences were identified with adverse events, including hypoglycemia, or LOS. Administration of SQ LAI < 12 hours did not decrease time to DKA resolution or LOS. Patients in the Early group had received a lower dose of LAI, shorter duration of CIVI infusion, and required less IV fluids within 36 hours of admission. This study supports the need for further research to determine the potential benefits of administering SQ insulin early in managing DKA.

Acute cyanide intoxication due to apricot seed ingestion.

Introduction: Cyanide poisoning, whether it be accidental or intentional, remains a significant danger to adults and children, especially in societies where agriculture is a primary source of income. We examined the clinical follow-up, complications, and results of cyanide poisoning cases that occurred after eating the pits and seeds of plants containing cyanide glycosides, such as apricot kernels and almonds. Methods: Between 01/01/2017 and 01/08/2022, 14 children aged 1-18 years who were followed up with a prediagnosis of cyanide poisoning in our Paediatric Intensive Care Unit (PICU) were retrospectively analysed. Results: Eight of the patients followed with a preliminary diagnosis of cyanide poisoning were female and six were male. The most common admission month was July (42.8%) coinciding with the agricultural season. The most common symptoms at presentation were weakness and fatigue (n = 7). In the PICU, 4 patients presented lip cyanosis; 3, altered level of consciousness. Vomiting, seizure, headache, dizziness and palpitatons were less frequent. Four patients were treated with hydroxocobalamin (Cyanokit®) as an antidote due to acidosis in their blood gases. All patients treated for cyanide poisoning were discharged. Conclusions: Cyanide poisoning should be considered in paediatric patients with suspicious findings, sudden loss of consciousness, increased anion gap acidosis and lactic acidosis. The history of eating the seeds of plants such as apricot and almonds should be investigated.

Serum Anion Gap at Admission Predicts All-Cause Mortality in Critically Ill Patients With Cirrhosis: A Retrospective Cohort Study.

The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis. A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values. Cox regression and Kaplan-Meier survival analysis were used to assess the relationships between AG levels and outcomes. Both cohorts showed strong parameter similarity ( P > 0.05). High AG was associated with significantly lower survival probabilities. Cox models confirmed elevated AG as a risk factor, even after adjusting for covariates (hazard ratio: 1.920, 1.793, and 1.764 for 30-day, 60-day, and hospital mortality, respectively). Subgroup analyses, especially regarding chronic kidney disease, revealed complex interactions. Serum AG displayed predictive power comparable with established scoring systems. Elevated AG at admission is a valuable predictor of poor outcomes and increased mortality risk in critically ill cirrhotic patients. Serum AG can serve as an easily accessible tool for risk assessment and prognosis evaluation in this population.

Hypokalemic paralysis and proximal renal tubular acidosis secondary to tenofovir-induced Fanconi syndrome: A contributing cause of death

Nucleotide reverse transcriptase inhibitors (NRTIs, primarily cidofovir and adefovir, less likely tenofovir) pose a well-known risk of nephrotoxicity. Acute renal failure, nephrogenic diabetes insipidus (NDI), and Fanconi syndrome (FS) are the primarily reported renal adverse effects associated with NRTIs. In this report, we describe a case of a 52-year-old female who presented to the outpatient department of a tertiary-care facility with polyuria, polydipsia, convulsions, myalgias, and hypokalemic paralysis (quadriparesis) after 10 months exposure to tenofovir disoproxil fumarate (TDF), which she was taking for HIV and Hepatitis-B virus coinfection. The patient developed hypokalemic paralysis and proximal renal tubular acidosis (pRTA) with normal anion gap hyperchloremic metabolic acidosis. On evaluation, renal tubulopathy was evident, which was resolved post-TDF discontinuation and therapeutic corrections. A diagnosis of TDF-induced FS, pRTA, and NDI were considered, as there were no clear alternative explanations. This report also highlights the characteristics of TDF-induced FS from the published case reports in the Indian context.

A case report of elevated bromide levels from pyridostigmine bromide for treatment of myasthenia gravis.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Elevated serum bromide levels can cause dermatological, gastrointestinal, and neurological abnormalities. As bromide and chloride are both halogens, bromide may interfere with chloride assays, causing a falsely high serum chloride concentration and a low or negative anion gap. There is a paucity of data describing bromide toxicity from high doses of pyridostigmine bromide (PB). This case report describes a patient with an elevated bromide level with neurological symptoms from a therapeutic dose of PB. A 37-year-old male with myasthenia gravis secondary to type B2 thymoma status following thymectomy presented in myasthenic crisis. He required mechanical ventilation and was managed with steroids, intravenous immune globulin, plasmapheresis, and PB. On day 9, the patient experienced acute agitation. He had an anion gap of 2 mEq/L and a chloride concentration of 109 mEq/L. The plasma creatinine concentration was 0.63 to 1.15mg/dL and urine output was 0.76 to 1.79mL/kg/h throughout his admission. All other laboratory values were normal. The daily dose of PB was 660mg on day 9, but the patient received 76mg of intravenous PB over the first few days of his admission with the largest dose in 24 hours equal to 48mg. On day 10, the patient's bromide level was 37 μg/mL. His agitation was initially managed with quetiapine, followed by PB dose reduction. To our knowledge, there are 2 cases in the literature of bromide toxicity secondary to PB. These patients experienced neurological symptoms with bromide levels of 88 to 90 μg/mL. Bromide concentrations of more than 12 μg/mL are associated with a higher risk of neuronal dysfunction demonstrated as disturbances on an electroencephalogram, and levels greater than 50 μg/mL are considered toxic. While our patient's bromide level was not as high as those previously reported, no other causes for his agitation were identified. Elevated bromide levels from therapeutic PB can occur, and monitoring of these levels should be considered.

Determining lactate concentrations in Korean indigenous calves and evaluating its role as a predictor for acidemia in calf diarrhea

BackgroundCalf diarrhea leads to high mortality rates and decreases in growth and productivity, causing negative effects on the livestock industry. Lactate is closely associated with metabolic acidosis in diarrheic calves. However, there have been no reports on lactate concentrations in Korean indigenous (Hanwoo) calves, especially those with diarrhea. This study aimed to determine the reference range of L-lactate and D-lactate concentrations in Hanwoo calves and to better understand the utility of lactate as predictive factors for acidemia in diarrheic calves.ResultsL-lactate and D-lactate concentrations were measured in healthy (n = 44) and diarrheic (n = 93) calves, and blood gas analysis was performed on diarrheic calves. The reference range in healthy calves was 0.2–2.25 mmol/L for L-lactate and 0.42–1.38 mmol/L for D-lactate. Diarrheic calves had higher concentrations of L-lactate and D-lactate than healthy calves. In diarrheic calves, L-lactate and D-lactate each had weak negative correlation with pH (r = − 0.31 and r = − 0.35). In diarrheic calves with hyper-L-lactatemia, the combined concentrations of L-lactate and D-lactate had moderate correlation with pH (r = − 0.51) and anion gap (r = 0.55). Receiver operating characteristic analysis showed D-lactate had fair predictive performance (AUC = 0.74) for severe acidemia, with an optimal cut-off value of > 1.43 mmol/L. The combined concentrations of L-lactate and D-lactate showed fair predictive performance for predicting acidemia (AUC = 0.74) and severe acidemia (AUC = 0.72), with cut-off values of > 6.05 mmol/L and > 5.95 mmol/L.ConclusionsThe determined reference ranges for L-lactate and D-lactate in Hanwoo calves enable the identification of hyper-L-lactatemia and hyper-D-lactatemia. Diarrheic calves exhibited increased lactate concentrations correlated with acid-base parameters. While the concentrations of L-lactate and D-lactate have limitations as single diagnostic biomarkers for predicting acidemia or severe acidemia, their measurement remains important, and L-lactate has the advantage of being measurable at the point-of-care. Assessing lactate concentrations should be considered by clinicians, especially when used alongside other clinical indicators and diagnostic tests. This approach can improve calf diarrhea management, contributing positively to animal welfare and providing economic benefits to farms.

Unsupervised machine learning to identify subphenotypes among cardiac intensive care unit patients with heart failure.

Hospitalized patients with heart failure (HF) are a heterogeneous population, with multiple phenotypes proposed. Prior studies have not examined the biological phenotypes of critically ill patients with HF admitted to the contemporary cardiac intensive care unit (CICU). We aimed to leverage unsupervised machine learning to identify previously unknown HF phenotypes in a large and diverse cohort of patients with HF admitted to the CICU. We screened 6008 Mayo Clinic CICU patients with an admission diagnosis of HF from 2007 to 2018 and included those without missing values for common laboratory tests. Consensus k-means clustering was performed based on 10 common admission laboratory values (potassium, chloride, anion gap, blood urea nitrogen, haemoglobin, red blood cell distribution width, mean corpuscular volume, platelet count, white blood cell count and neutrophil-to-lymphocyte ratio). In-hospital mortality was evaluated using logistic regression, and 1year mortality was evaluated using Cox proportional hazard models after multivariable adjustment. Among 4877 CICU patients with HF who had complete admission laboratory data (mean age 69.4years, 38.4% females), we identified five clusters with divergent demographics, comorbidities, laboratory values, admission diagnoses and use of critical care therapies. We labelled these clusters based on the characteristic laboratory profile of each group: uncomplicated (25.7%), iron-deficient (14.5%), cardiorenal (18.4%), inflamed (22.3%) and hypoperfused (19.2%). In-hospital mortality occurred in 10.7% and differed between the phenotypes: uncomplicated, 2.7% (reference); iron-deficient, 8.1% [adjusted odds ratio (OR) 2.18 (1.38-3.48), P<0.001]; cardiorenal, 10.3% [adjusted OR 2.11 (1.37-3.32), P<0.001]; inflamed, 12.5% [adjusted OR 1.79 (1.18-2.76), P=0.007]; and hypoperfused, 21.9% [adjusted OR 4.32 (2.89-6.62), P<0.001]. These differences in mortality between phenotypes were consistent when patients were stratified based on demographics, aetiology, admission diagnoses, mortality risk scores, shock severity and systolic function. One-year mortality occurred in 31.5% and differed between the phenotypes: uncomplicated, 11.9% (reference); inflamed, 26.8% [adjusted hazard ratio (HR) 1.56 (1.27-1.92), P<0.001]; iron-deficient, 33.8% [adjusted HR 2.47 (2.00-3.04), P<0.001]; cardiorenal, 41.2% [adjusted HR 2.41 (1.97-2.95), P<0.001]; and hypoperfused, 52.3% [adjusted HR 3.43 (2.82-4.18), P<0.001]. Similar findings were observed for post-discharge 1year mortality. Unsupervised machine learning clustering can identify multiple distinct clinical HF phenotypes within the CICU population that display differing mortality profiles both in-hospital and at 1year. Mortality was lowest for the uncomplicated HF phenotype and highest for the hypoperfused phenotype. The inflamed phenotype had comparatively higher in-hospital mortality yet lower post-discharge mortality, suggesting divergent short-term and long-term prognosis.

Clinical characteristics and genetic profile of children with WDR72-associated distal renal tubular acidosis: a nationwide experience.

Limited data, primarily from small case series, exist regarding the clinical profile, genetic variants, and outcomes of WDR72-associated distal renal tubular acidosis (WDR72-dRTA). Our study enrolled children diagnosed with WDR72-dRTA below 18years of age from 9 Indian centers and analyzed their clinical characteristics, genetic profiles, and outcomes. Potential genotype-phenotype correlations were explored. We report 22 patients (59% female) with WDR72-dRTA who were diagnosed at a median age of 5.3 (3, 8) years with polyuria (n = 17; 77.3%), poor growth (16; 72.7%), and rickets (9; 40.9%). Amelogenesis imperfecta was present in 21 (95.5%) cases. At presentation, all patients had normal anion gap metabolic acidosis; hypokalemia and nephrocalcinosis were seen in 17 (77.3%) patients each. Seven (31.8%) patients had concomitant proximal tubular dysfunction. Genetic analysis identified biallelic nonsense variants in 18 (81.8%) patients, including novel variants in 6 cases. A previously reported variant, c.88C > T, and a novel variant, c.655C > T, were the most frequent variants, accounting for 10 (45.5%) cases. Over a median follow-up of 1.3 (1, 8) years, the height velocity improved by 0.74 (0.2, 1.2) standard deviation scores, while 3 children (13.6%) progressed to chronic kidney disease (CKD) stage 2, with eGFR ranging from 67 to 76mL/min/1.73 m2, respectively, after 11.3-16years of follow-up. No specific genotype-phenotype correlation could be established. WDR72-dRTA should be considered in children with typical features of amelogenesis imperfecta and dRTA. Biallelic nonsense variants are common in Asians. While most patients respond well to treatment with improved growth and preserved eGFR, on long-term follow-up, a decline in eGFR may occur.

Balanced Fluids Versus Normal Saline for Initial Fluid Resuscitation in Adults With Diabetic Ketoacidosis.

Background: Normal saline (NS) has been the choice fluid for volume resuscitation in diabetic ketoacidosis (DKA) for decades. Large volume resuscitation with NS can lead to hyperchloremic metabolic acidosis and is associated with a higher incidence of major adverse kidney events compared to balanced fluids (BF). Objective: Compare safety and effectiveness of fluid resuscitation with BF vs NS in adult patients with DKA. Methods: Single-center retrospective cohort study evaluated patients who received NS or BF for DKA treatment between July 2020 and August 2021. Primary endpoint was time to DKA resolution. Secondary endpoints included time to anion gap ≤12, HCO3 ≥15 and ≥18mmol/L, acute kidney injury, and hospital and intensive care unit length of stay. Results: 110 patients were included (NS 55% (n = 60), BF 45% (n = 50)). Time to DKA resolution was faster in patients who received BF vs NS (13 (10 - 19) hours vs 17 (11 - 25) hours, P = 0.02). Treatment with NS was associated with a longer time to resolution of DKA when adjusted for initial bicarbonate and AKI at admission. Conclusion: BF was associated with a shorter time to DKA resolution compared to NS.