The Incidence and Risk Factors of Refeeding Syndrome-like Hypophosphatemia in Inflammatory Bowel Disease: A Preliminary Study.

BACKGROUND AND AIMS: Refeeding syndrome (RFS) is defined by the presence of acute electrolyte disturbances, including hypophosphatemia. Underlying disease(s), malnutrition and hospitalisation are known risk factors for RFS. It can occur in patients with inflammatory bowel disease (IBD). We aimed to determine the frequency of hypophosphatemia and the relationship between hypophosphatemia, disease severity and nutritional status in hospitalized patients with IBD. METHODS: This study was performed prospectively in hospitalized adult patients for the treatment of IBD in a tertiary-care hospital. Disease severity was assessed using Truelove and Witts score for ulcerative colitis (UC) and Crohn's Disease Activity Index for Crohn's disease (CD). Nutritional status was determined using Subjective Global Assessment (SGA). Serum phosphate concentration was recorded for first 7 days after hospitalization, and less than 0.65 mmol/l was defined as hypophosphatemia. RESULTS: Fifty participants (33 with UC and 17 with CD) were included in the study. The mean age of the study sample was 43.4±14.9 years, of which 64% were male. A total of 8.8% of patients with UC and 37.5% of patients with CD had severe (>moderate) disease upon study admission. Seventeen patients (34%) were malnourished. During the 7 study days, 23 participants (46%) had at least one episode of hypophosphatemia. Serum phosphate concentration was significantly and moderately correlated with serum potassium concentration in both the patients and the hypophosphatemia group on study day 3 (p<0.05). Multivariate logistic regression analysis showed that the presence of malnutrition [odds ratio (OR) = 3.64, 95% confidence interval (CI): 1.52-5.58, p=0.008), the administration of parenteral nutrition (OR=2.91, 95%Cl: 1.37-4.63, p=0.015), and severe IBD (OR=1.74, 95%CI: 1.03-3.42, p=0.020) were associated with hypophosphatemia. CONCLUSIONS: Approximately half of the participants exhibited at least one instance of hypophosphatemia during the study period. Hypophosphatemia was found to be associated with malnutrition, parenteral nutrition, and severe disease in patients with IBD requiring hospitalization.

Hypophosphatemia Correction Reduces ICANS Incidence and Duration in CAR T-cell Therapy: A Pooled Clinical Trial Analysis.

A common complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS), which presents with encephalopathy, aphasia, inattention, somnolence, seizures, weakness, or cerebral edema. Despite its significant morbidity, there are currently no effective targeted treatments. Given the clinical similarities between ICANS and the neurological manifestations of acute hypophosphatemia, we retrospectively reviewed 499 patients treated with CD19-targeted CAR T-cell therapy across multiple clinical trials between 2015 and 2020. In addition to clinical toxicities experienced by the patients, we also interrogated the impact of serum electrolyte data and repletion of corresponding electrolyte deficiencies with ICANS incidence, severity, and duration. Hypophosphatemia was a common occurrence in CAR T-cell recipients and the only electrolyte derangement associated with a significantly higher cumulative incidence of ICANS. Moreover, phosphorus repletion in patients with hypophosphatemia was associated with significantly decreased ICANS incidence and duration. Hypophosphatemia was uniquely associated with encephalopathy neurological adverse events, which also showed the strongest positive correlation with both ICANS and cytokine release syndrome severity. These findings suggest that serum phosphorus could be a reliable biomarker for ICANS, and expeditious, goal-directed phosphorus repletion in response to serum hypophosphatemia could be a safe, inexpensive, and widely available intervention for such patients. SIGNIFICANCE: Herein we show that phosphorus repletion in patients with hypophosphatemia receiving anti-CD19 chimeric antigen receptor T-cell therapeutics was associated with significantly decreased immune effector cell-associated neurotoxicity syndrome (ICANS) incidence and symptom duration. Given the significant morbidity associated with ICANS and lack of targeted interventions, hypophosphatemia may serve as both a useful biomarker and an inexpensive intervention for ICANS.

Electrolyte and Acid-Base Abnormalities After Kidney Transplantation.

Kidney transplantation is the optimal therapeutic approach for individuals with end-stage kidney disease. The Scientific Registry of Transplant Recipients has reported a continuous rise in the total number of kidney transplants performed in the United States, with 25,500 new kidney recipients in 2022 alone. Despite an improved glomerular filtration rate, the post-transplant period introduces a unique set of electrolyte abnormalities that differ from those encountered in chronic kidney disease. A variety of factors contribute to the high prevalence of hypomagnesemia, hyperkalemia, metabolic acidosis, hypercalcemia, and hypophosphatemia seen after kidney transplantation. These include the degree of allograft function, immunosuppressive medications and their diverse mechanisms of action, and metabolic changes after transplant. This article aims to provide a comprehensive review of the key aspects surrounding the most commonly encountered electrolyte and acid-base abnormalities in the post-transplant setting.

Contributing factors to hypophosphatemia development in critically Ill ventilated patients: a retrospective cohort study.

Hypophosphatemia (serum phosphate < 2.5 mg/dL) is a major concern when initiating nutritional support. We evaluated which factors contribute to hypophosphatemia development in critically ill patients, as well as the association between hypophosphatemia and mortality. A retrospective cohort study of patients who were ventilated for at least 2 days in a 16-bed mixed ICU. Data collected includes demographics, Acute Physiology & Chronic Health Evaluation 2 (APACHE2) admission score, Sequential Organ Failure Assessment score at 24 h (SOFA24), hourly energy delivery, plasma phosphate levels during the first 2 weeks of admission, ICU length of stay (LOS), length of ventilation (LOV), and mortality (ICU and 90 days). For the hypophosphatemia development model, we considered mortality as a competing risk. For mortality analysis, we used the Cox proportional hazards model considering hypophosphatemia development as a time-varying covariate. 462 patients were used in the analysis. 59.52% of the patients developed hypophosphatemia. Several factors were associated with a decreased risk of hypophosphatemia: age, BMI, pre-admission diabetes diagnosis, APACHE2, SOFA24, first kidney SOFA score, hospital admission time before ICU admission, and admission after liver transplantation. Admission due to trauma was associated with an increased risk of hypophosphatemia. Survival analysis with hypophosphatemia as a time-varying covariate showed a protective effect of hypophosphatemia from mortality (HR 0.447, 95% CI 0.281, 0.712). Age, APACHE2, and SOFA24 score were found to be significantly associated with ICU mortality. Fasting duration in the ICU before nutritional support initiation was not found to be significantly associated with hypophosphatemia. We examined several fasting intervals (12 h, 24 h, 36 h, 48 h, 60 h, 72 h). In each fast interval, we compared the prevalence of hypophosphatemia among patients who fasted the specified length of time, with those who did not fast for the same length of time. In each fasting interval, hypophosphatemia prevalence was lower in the fasting group compared to the non-fasting group. However, this difference was insignificant. BMI, APACHE2, and hospital LOS before ICU admission were inversely associated with hypophosphatemia development. Fasting for up to 72 h in the ICU before starting nutritional support did not affect hypophosphatemia occurrence. Hypophosphatemia was associated with lower mortality.

Prospective multicenter study to describe the prevalence, outcomes, and management of phosphate disorders in intensive care patients: Study protocol for part B of the international GUTPHOS study.

BACKGROUND: Aberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes. METHODS: This multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe). DISCUSSION: The GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial. CLINICAL TRIAL REGISTRY: NCT05909722.

The association between serum phosphate and length of hospital stay and all-cause mortality in adult patients: a cross-sectional study.

BACKGROUND: Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients. METHODS: This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64-0.8 mmol/L; G3, iP 0.8-1.16 mmol/L; G4, iP 1.16-1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records. RESULTS: A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An "L-shaped" non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4. CONCLUSIONS: Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention.

Hypophosphataemia and late-onset sepsis in extremely preterm neonates: A case-control study.

AIM: Late-onset sepsis (LOS) is common in extreme prematurity. These infants are at risk of refeeding syndrome-associated hypophosphataemia. Our objective was to investigate whether hypophosphataemia predisposes to LOS in extremely premature neonates. METHODS: A retrospective case-control study of neonates born before 29 weeks' gestation in an Australian NICU from 2016 to 2020. Cases developed LOS or localised infection. Two controls, matched within 2 gestational weeks and 90 calendar days, were selected per case. RESULTS: Amongst 48 cases and 93 controls, cases were smaller at birth (767 g vs. 901 g, P = 0.01), but were otherwise comparable. Hypophosphataemia was more common in cases (26% vs. 15%, P = 0.18). Increased intravenous protein intake in the first week was protective against LOS (OR = 0.9, 95% CI 0.76-1.00, P = 0.04); median 2.1 g/kg/day in cases, 2.3 g/kg/day in controls. CONCLUSIONS: Hypophosphataemia as part of refeeding syndrome is prevalent and under-recognised in extremely premature neonates. We did not find an association between hypophosphataemia and LOS. Low intravenous protein may be an independent risk factor for infection.

[Prevalence of hypophosphatemia in children with diabetic ketoacidosis and treatment with subcutaneous regular insulin. Observational study]. / Prevalencia de Hipofosfatemia en niños con cetoacidosis diabética y tratamiento con insulina regular subcutánea. Estudio observacional.

Diabetic ketoacidosis (DKA) is one of the most serious complications of type 1 diabetes mellitus. Its treatment requires fluid and electrolyte replacement and insulin. Hypophosphatemia as a complication of treatment has been scarcely evaluated. OBJECTIVES: To estimate the incidence of hypophosphatemia in children with DKA, treated with subcutaneous regular insulin (IRS), and to explore factors associated with this complication. PATIENTS AND METHOD: Prospective, observational study. Patients diagnosed with DKA hospitalized in the general care ward were included. Data on phosphatemia, glycemia, acid-base status, and IRS amount (U/kg) received were recorded at baseline and after 24 h of treatment. Hypophosphatemia was defined as values below 2.5 mg/dl. The correlation between initial phosphate and at 24 h of treatment was evaluated; the incidence of hypophosphatemia at 24 h was expressed as a percentage of the total number of patients. RESULTS: 30 patients were included, 15 were female, mean age 11.4 ± 3.2 years. At 24 h of treatment with IRS, 36.7% (95%CI 22-55%) presented hypophosphatemia, mean value 1.9 ± 1.5 mg/dl. Initial bicarbonate < 10 mmol/L acted as a predictor of hypophosphatemia (OR 7.5; 95%CI 1.4-39.8%; p = 0.01). No patient required intravenous phosphate correction, and no associated clinical complications were observed. CONCLUSION: In the group studied, the incidence of hypophosphatemia reached 36.7% at 24 hours of treatment. Initial bicarbonate lower than 10 mmol/L was significantly associated with hypophosphatemia. No complications associated with hypophosphatemia were observed.

Medical and Psychiatric Characteristics of Patients Hospitalized for Severe Restrictive Eating Disorders: Analysis of 545 Consecutive Patients with Severe Anorexia Nervosa or Avoidant/Restrictive Food Intake Disorder.

BACKGROUND: People with severe eating and feeding disorders regularly require hospitalization due to complications inherent to their disease, though formal training regarding this care is limited. METHODS: This retrospective study included 545 patients with severe anorexia nervosa (AN) or avoidant restrictive food intake disorder hospitalized in a medical stabilization unit between 2018 and 2021. Biometrics were obtained throughout hospitalization. Nutrition was increased until patients were gaining 0.2 kg/day. RESULTS: Average admission body mass index was 13 kg/m2 with diagnoses of 46% AN-R (restricting), 39% AN-BP (binge-purge), and 15% avoidant restrictive food intake disorder. Average daily Kcals by discharge were 3343 for females and 3962 for males; 26% required nasogastric feeding. Hypoglycemia was common until day 7, correlated with elevated liver function tests and low prealbumin. Liver function tests were abnormal in 31% of patients. Refeeding hypophosphatemia developed in 26% of patients starting day 2 and was associated with lower body mass index. Hypokalemia appeared on admission among 39%, twice as common in patients diagnosed with AN-BP. Initial electrocardiograms were abnormal in 50% of patients, usually sinus bradycardia. Average QTc was normal, but only 14% prolonged. Bone density testing revealed 70% osteoporosis. History of suicide attempts were present in 19%, while 76% and 50% presented with anxiety and depressive disorders, respectively. CONCLUSIONS: Given the inextricability of medical complications from severe eating and feeding disorders, familiarity among consult-liaison psychiatrists with the prevalence of frequently observed abnormal findings can inform consultation, prevent adverse events, prevent unnecessary intervention, and facilitate weight restoration and medical stabilization.

Incidence of hypophosphataemia after ICU admission in mechanically ventilated patients and its relationship with risk factors for refeeding syndrome.

OBJECTIVE: To describe the incidence of hypophosphatemia in patients admitted to the ICU who have required mechanical ventilation. To analyze the presence of risk factors and its relationship with nutritional practice. DESIGN: Prospective observational study. SETTING: Polyvalent ICUs of 2 University Hospitals. PATIENTS OR PARTICIPANTS: Patients on invasive mechanical ventilation ≥72 h with normal level of phosphorus at admission. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Electrolyte levels (phosphorus, magnesium, potassium) were determined on admission to the ICU and at 96 h. Risk categories on admission, caloric intake, insulin doses and acid-base status during the first 4 days of admission were recorded. Incidence was calculated as the number of patients who developed hypophosphataemia after admission. Univariate analysis was performed for between-group comparison and multivariate analysis of potential risk factors. RESULTS: 89 patients were included. The incidence of hypophosphataemia was 32.6%. In these patients phosphorus decreased from 3.57 ±â€¯1.02 mmol/l to 1.87 ±â€¯0.65 mmol/l (52.3%). The mean kcal/kg/24 h provided in the first 4 days was 17.4 ±â€¯4.1, with no difference between the group that developed hypophosphataemia and the group that did not. Significant risk factors were insulin doses administered and pH and PaCO2 values. CONCLUSIONS: The incidence of hypophosphataemia at 96 h from admission in mechanically ventilated patients is high and unrelated to the risk category and hypocaloric nutritional practice used. Insulin dosis and acid-base status are the main determinants of its occurrence.

Prevalence of FGF23 elevation in patients with hypophosphatemia.

BACKGROUND AND AIMS: To investigate the contribution of FGF23 in explaining the cases of hypophosphatemia observed in clinical practice, we aimed to determine for the first time the prevalence of FGF23 elevation in patients with hypophosphatemia and to describe the different mechanisms of FGF23-related hypophosphatemic disorders. MATERIALS AND METHODS: We performed a prospective, observational, multicenter, cohort study of 260 patients with hypophosphatemia. Blood measurements (PTH, 1,25-dihydroxyvitamin D, bone alkaline phosphatase, 25-hydroxyvitamin D, and FGF23) were performed on a Liaison XL® (DiaSorin) analyzer. RESULTS: Primary elevation of FGF23 (>95.4 pg/mL) was reported in 10.4% (95CI: 7.0-14.7) of patients (n = 27) with hypophosphatemia, suggesting that at least 1 in 10 cases of hypophosphatemia was erroneously attributed to an etiology other than FGF23 elevation. Patients with elevated blood FGF23 were grouped according to the etiology of the FGF23 elevation. Thus, 10 patients had a renal pathology, chronic kidney disease or post-renal transplantation condition. The remaining patients (n = 17) had the following etiologies: malignancies (n = 9), benign pancreatic tumor (n = 1), post-cardiac surgery (n = 4), cirrhosis (n = 2), and chronic obstructive pulmonary disease (n = 1). CONCLUSION: In order to improve patient management, it seems essential to better integrate plasma FGF23 measurement into the routine evaluation of hypophosphatemia.

Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

Incidence and Prevalence of Fibrous Dysplasia/McCune-Albright Syndrome: A Nationwide Registry-Based Study in Denmark.

CONTEXT: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD/MAS, absence of registries, heterogeneous presentation, and possibly asymptomatic phenotype. FD/MAS may present with FGF23-mediated hypophosphatemia, of which the epidemiology is also unclear. OBJECTIVE: Evaluate incidence and prevalence of FD/MAS and FD/MAS-related hypophosphatemia. METHODS: This cohort study based on the nationwide Danish National Patient Registry from 1995-2018, included patients identified by ICD-10 codes M85.0 (monostotic FD [MFD]) and Q78.1 (polyostotic FD [PFD]/MAS). Incidence rates and prevalence were calculated and stratified by sex, age, calendar period, and diagnosis code. Cases were screened for FD-associated hypophosphatemia by diagnosis code E.83 (disorder of mineral metabolism) and dispatched vitamin D analogues. RESULTS: A total of 408 patients were identified, 269 with MFD (66%), 139 with PFD/MAS (34%), comparable between sexes. Incidence of FD/MAS demonstrated increasing secular trend with a rate of 3.6 per 1 000 000 person-years (95% CI: 2.9, 4.5) in 2015-2018. Incidence peaked between age 11 and 20. Prevalence of FD/MAS increased over time to 61.0 (95% CI: 54.6, 67.4) per 1 000 000 persons in 2018. The incidence rate of MFD was 1.5-fold that of PFD/MAS in the first decade, rising to 2.5-fold in the last decade. No FD/MAS cases were registered with diagnosis code or treatment for hypophosphatemia. CONCLUSION: FD/MAS is rare, diagnosis peaks during adolescence without sex predominance, and MFD is most prevalent. Hypophosphatemia may be underdiagnosed and undertreated, or it may be underregistered, comparing this study to literature.

The impact of tubular dysfunction and its relationship with acute kidney injury in children.

BACKGROUND: Tubular dysfunction can cause electrolyte disturbances with potentially serious consequences. We studied the epidemiology and outcomes of electrolyte disturbances and tubular dysfunction among critically ill children and evaluated their relationships with acute kidney injury (AKI). METHODS: We conducted a prospective cohort study recruiting children aged 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (PICU) from 6/2020 to 6/2021. The serum levels of sodium, potassium, calcium, phosphate, and magnesium were reviewed and simultaneous urinary investigations for tubular function were performed among children with electrolyte disturbances. RESULTS: Altogether there were 253 episodes of admission. The median (interquartile) age was 4.9 (1.3-11.0) years and 58.1% were male. The median number of electrolyte disorders was 3 (2-4) types. Hypophosphatemia (74.2%), hypocalcemia (70.3%) and hypermagnesemia (52.9%) were the three commonest types of disturbances. Urinary electrolyte wasting was commonly observed among children with hypomagnesemia (70.6%), hypophosphatemia (67.4%) and hypokalemia (28.6%). Tubular dysfunction was detected in 82.6% of patients and urinary ß2-microglobulin level significantly correlated with the severity of tubular dysfunction (p < 0.001). The development of tubular dysfunction was independent of AKI status. Tubular dysfunction was associated with mortality (p < 0.001) and was an independent predictor of PICU length of stay (LOS) (p < 0.001). The incorporation of the tubular dysfunction severity into the AKI staging system improved the prediction of PICU LOS. CONCLUSIONS: Tubular dysfunction was associated with both morbidity and mortality in critically ill children and its assessment may help to capture a more comprehensive picture of acute kidney insult.

Refeeding Hypophosphatemia in Oldest Old Critically Ill Patients.

BACKGROUND: Refeeding syndrome is characterized by metabolic and electrolyte alterations that result from the initiation of feeding after a period of inadequate caloric intake. Especially, in the elderly with acute and/or chronic illness, nutritional deficiencies are common, and diminished oral intake with effects of catabolic status yields malnutrition. This study was conducted to evaluate refeeding hypophosphatemia and its consequences on outcomes in the oldest old critically ill patients. METHODS: This study was designed as a retrospective cohort study that included patients who were 80 years old or older admitted to ICU. Patients were grouped depending on whether hypophosphatemia occurred after 48 hours of admission who started feeding. RESULTS: The median age of all patients was 87[82-90] years and 61(73%) of them were female. Refeeding hypophosphatemia was observed in 25(30%) patients. When patients were grouped depending on the occurrence of hypophosphatemia, groups were similar according to the severity scores, and comorbidities. Neither ICU mortality nor hospital mortality was different between groups (p=0.76 and p=0.19, respectively). CONCLUSION: Refeeding hypophosphatemia incidence was similar to previous studies, although study patients were the highest risk group. Outcome parameters including mortality rate and length of ICU stay were not different between patients with or without refeeding hypophosphatemia.

Incidence of Hypophosphatemia After Intravenous Administration of Iron: A Matching-Adjusted Indirect Comparison of Data from Japanese Randomized Controlled Trials.

INTRODUCTION: Intravenous (IV) administration of iron is considered a safe and efficacious treatment for iron deficiency anemia (IDA), recommended in patients requiring rapid replenishment of iron, or intolerant or unresponsive to oral administration of iron. Recent randomized controlled trials (RCTs) have shown high incidence of hypophosphatemia after administration of two IV iron preparations: saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM). The present study aimed to conduct matching-adjusted indirect comparison (MAIC) of hypophosphatemia incidence with these iron formulations and ferric derisomaltose (FDI) based on data from head-to-head RCTs conducted in Japan. METHODS: A MAIC of hypophosphatemia incidence was conducted on the basis of data from two head-to-head RCTs. The relative odds of hypophosphatemia with FDI versus SFO were obtained from patient-level data from a recent RCT and adjusted for cumulative iron dose, while parametric models of serum phosphate levels from a separate RCT were used to estimate the relative odds of hypophosphatemia with FCM with SFO. An anchored MAIC was then conducted comparing FDI with FCM. RESULTS: The adjusted odds of experiencing hypophosphatemia were significantly lower with FDI than SFO [odds ratio (OR) of 0.02; 95% confidence interval (CI) 0.01-0.05]. The parametric models of serum phosphate from the RCT comparing FCM with SFO provided an estimated OR of 1.17 for the incidence of hypophosphatemia with FCM versus SFO. Combining the two estimates in the MAIC showed that the odds of experiencing hypophosphatemia would be 52.5 (95% CI 27.7-99.4) times higher with FCM than FDI in patients with IDA associated with heavy menstrual bleeding in Japan. CONCLUSIONS: Direct comparison of patient-level data and a MAIC from two RCTs in Japanese patients with heavy menstrual bleeding indicated that hypophosphatemia is less frequent in patients treated with FDI than those with FCM or SFO. Results are in agreement with RCTs comparing FDI and FCM in patients with various etiologies conducted in the USA and Europe.

Elevated morbidity and mortality in patients with chronic idiopathic hypophosphatemia: a nationwide cohort study.

Background: Chronic idiopathic hypophosphatemia (CIH) induced by X-linked hypophosphatemic rickets or tumor-induced osteomalacia is a rare inherited or acquired disorder. However, due to its rarity, little is known about the epidemiology and natural course of CIH. Therefore, we aimed to identify the prevalence and long-term health outcomes of CIH patients. Methods: Using the Korean Health Insurance Review and Assessment claims database, we evaluated the incidence of hypophosphatemia initially diagnosed from 2003 to 2018. After excluding secondary conditions that could change serum phosphorus levels, we identified 154 patients (76 men and 78 women) with non-secondary and non-renal hypophosphatemia. These hypophosphatemic patients were compared at a ratio of 1:10 with age-, sex-, and index-year-matched controls (n = 1,540). Results: In the distribution of age at diagnosis, a large peak was observed in patients aged 1-4 years and small peaks were observed in ages from 40-70 years. The age-standardized incidence rate showed non-statistically significant trend from 0.24 per 1,000,000 persons in 2003 to 0.30 in 2018. Hypophosphatemic patients had a higher risk of any complication (adjusted hazard ratio [aHR], 2.17; 95% confidence interval [CI], 1.67-2.69) including cardiovascular outcomes, chronic kidney disease, hyperparathyroidism, osteoporotic fractures, periodontitis, and depression. Hypophosphatemic patients also had higher risks of mortality and hospitalization than the controls (aHR, 3.26; 95% CI, 1.83-5.81; and aHR, 2.49; 95% CI, 1.97-3.16, respectively). Conclusion: This first nationwide study of CIH in South Korea found a bimodal age distribution and no sex differences among patients. Hypophosphatemic patients had higher risks of complications, mortality, and hospitalization compared to age- and sex-matched controls.

Incidence and predictors of hypophosphataemia after ferric carboxymaltose use-A 3-year experience from a single institution in Singapore.

Ferric carboxymaltose (FCM) administration helps reduce transfusion requirements in the perioperative situation, which improves patient outcomes and reduces healthcare costs. However, there is increasing evidence of hypophosphataemia after FCM use. We aim to determine the incidence of hypophosphataemia after FCM administration and elucidate potential biochemical factors associated with the development of subsequent hypophosphataemia. A retrospective review of anonymised data of all FCM administrations in a single institution was conducted from August 2018 to August 2021. Each unique FCM dose administered was examined to assess its effect on Hb and serum phosphate levels within the subsequent 28 days from each FCM administration. Phosphate levels were repeatedly measured within the 28-day interval and the lowest phosphate level within that period was determined. Patients' serum phosphate levels within 28 days of FCM administration were compared against normal serum phosphate levels within 2 weeks before FCM administration. The odds ratios of various pre-FCM serum markers were calculated to elucidate potential biochemical predictors of post-FCM hypophosphataemia. In 3 years, a total of 1296 doses of FCM were administered to 1069 patients. The mean improvement in Hb was 2.45 g/dL (SD = 1.94) within 28 days of FCM administration, with the mean time taken to peak Hb levels being 6.3 days (SD = 8.63), which is earlier than expected, but was observed in this study and hence reported. The incidence of hypophosphataemia <0.8 mmol/L was 22.7% (n = 186), and <0.4 mmol/L was 1.6% (n = 9). This figure is lower than the numbers reported in previously published meta-analyses given that routine checks of serum phosphate levels were not conducted initially and hence could possibly be higher. The odds of developing hypophosphataemia (<0.8 mmol/L) were 27.7 (CI: 17.3-44.2, p < 0.0001) if baseline serum phosphate was less than 1 mmol/L. The odds of developing hypophosphataemia (<0.8 mmol/L) were 1.3 (CI: 1.08-1.59, p < 0.01) if the change in Hb levels observed after FCM administration were more than 4 g/dL. Hypophosphataemia after FCM administration is significant and FCM should be used by clinicians with caution.

Hypophosphatemia in infants with severe bronchiolitis and association with length of mechanical ventilation.

OBJECTIVES: Electrolyte disorders occurs frequently in children with bronchiolitis. The aim of the present study was to describe the frequency of hypophosphatemia and to evaluate its association with length of mechanical ventilation in infants admitted to a pediatric intensive care unit (PICU) with bronchiolitis. METHODS: This retrospective cohort study included infants aged between 7 days and 3 months admitted to a PICU between September 2018 and March 2020 and diagnosed with severe acute bronchiolitis requiring respiratory support. Infants with a chronic condition that could potentially be a confounding factor were excluded. The primary outcome was the frequency of hypophosphatemia (<1.55 mmol/L); the secondary outcomes were the frequency of hypophosphatemia during the PICU stay, and the association with length of mechanical ventilation (LOMV). RESULTS: Among the 319 infants admitted 178 had at least one phosphatemia value and were included in the study. The frequency of hypophosphatemia was 41% at PICU admission (61/148) and 46% during the PICU stay (80/172). The median [IQR] LOMV was significantly longer in children with hypophosphatemia at admission (109 [65-195] h vs. 67 [43-128] h, p = 0.007), and in multivariable linear regression lower phosphatemia at admission was associated with longer LOMV (p < 0.001) after controlling for severity (PELOD2 score) and weight. CONCLUSION: Hypophosphatemia was frequent in infants with severe bronchiolitis admitted to a PICU and was associated with a longer LOMV.

Hypophosphataemia definitions, incidence and associated outcomes in paediatric intensive care: A retrospective cohort study in post-cardiac surgical patients <2 years of age.

AIM: Hypophosphataemia has been linked to higher morbidity and mortality in intensive care but there is inconsistency in the definition of hypophosphataemia for infants and children. We aimed to determine the incidence of hypophosphataemia in a group of at-risk children in paediatric intensive care unit (PICU) and associations with patient characteristics and clinical outcomes using three different hypophosphataemia thresholds. METHODS: Retrospective cohort study of 205 post-cardiac surgical patients <2 years of age admitted to Starship Child Health PICU, Auckland, New Zealand. Patient demographics and routine daily biochemistry for 14 days after PICU admission were collected. Rates of sepsis, mortality and length of mechanical ventilation were compared between groups with different serum phosphate concentrations. RESULTS: Out of 205 children, 6 (3%), 50 (24%) and 159 (78%) had hypophosphataemia at thresholds of <0.7, <1.0 and <1.4 mmol/L, respectively. There were no differences in gestational age at birth, sex, ethnicity or mortality in those with and without hypophosphataemia at any threshold. Children with a serum phosphate <1.4 mmol/L had more mean (SD) total hours of mechanical ventilation (85.2 (79.6) vs. 54.9 (36.2) h, P = 0.02) and those with mean serum phosphate <1.0 mmol/L had more mean hours of mechanical ventilation (119.4 (102.8) vs. 65.2 (54.8) h, P < 0.0001), episodes of sepsis (14% vs. 5%, P = 0.03) and longer length of stay (6.4 (4.8-20.7) vs. 4.9 (3.9-6.8) days, P = 0.02). CONCLUSIONS: Hypophosphataemia is common in this PICU cohort and serum phosphate <1.0 mmol/L is associated with increased morbidity and length of stay.