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.

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.

Quality improvement project in a neonatal intensive care unit reduced the prevalence and duration of hypophosphatemia with significant and sustainable results.

BACKGROUND: Hypophosphatemia is associated with prolonged mechanical ventilation and may affect growth, bone mineralization, nephrocalcinosis, and mortality in preterm infants. Optimal nutrition practices may decrease risk for hypophosphatemia and improve outcome. METHODS: A quality improvement project was established to improve parenteral and enteral phosphorus intake with the goal to decrease prevalence and duration of hypophosphatemia in the first 14 days in infants <32 weeks' gestation. RESULTS: Among 406 preterm infants, the prevalence of moderate hypophosphatemia decreased from 44% to 19% (P < 0.01) over 4 years. The median duration of moderate hypophosphatemia decreased from 72 h (48-128) to 24 (24-53) (P < 0.01). Daily intakes of parenteral calcium and phosphorus on the fourth day of life increased from 1.5 to 2.5 mEq/kg/day (P < 0.01) and 0.6 to 1.3 mmol/kg/day (P < 0.01), respectively. The median postnatal age of first serum phosphorus concentration assessment decreased from 53 h (41-64) to 32 (24-40) (P < 0.01). CONCLUSION: During this quality improvement project, reduced prevalence and duration of hypophosphatemia in infants <32 weeks' gestation in the first 14 days of life was achieved through the optimization of parenteral and enteral phosphorus intake and improved response to acute hypophosphatemia.

Incidence, evolution and risk factors of hypophosphatemia in patients with solid tumors receiving ferric carboxymaltose: a retrospective cohort study.

OBJECTIVES: Ferric carboxymaltose (FCM) is increasingly used in the management of cancer-related anemia, yet it may cause hypophosphatemia. This retrospective study describes the incidence, evolution and risk factors of hypophosphatemia in a cohort of patients with solid tumors receiving FCM. METHODS: Serum phosphorus concentration was assessed longitudinally using a random intercepts model. The probability of developing hypophosphatemia, as graded by CTCAE version 4.0, was investigated using a multi-state model. Transition hazards were modeled non-parametrically and semi-parametrically by a Cox model. Causal marginal risk differences between baseline interventions on serum phosphorus and/or FCM dose were obtained via G-computation. RESULTS: In 174 ambulatory patients with solid tumors receiving FCM at two university hospitals between October 2020 and September 2021, the risk of developing moderate-to-severe hypophosphatemia was 36.0% (95% confidence interval (CI) 28.2-43.9%) and peaked within 16 days after first FCM administration. The average duration of moderate-to-severe hypophosphatemia was 12.4 days. After adjustment for confounders, lower baseline serum phosphorus (adjusted hazard ratio (aHR) 0.88 per 0.1 mmol/L increase, 95% CI 0.79-0.98) and higher FCM dose (first dose: aHR 1.12 per 1 mg/kg increase, 95% CI 1.01-1.25; second dose: aHR 1.06 per 1 mg/kg increase, 95% CI 1.00-1.13) significantly increased the hazard of moderate-to-severe hypophosphatemia. CONCLUSION: Approximately one out of three ambulatory patients with solid tumors may develop moderate-to-severe hypophosphatemia after FCM administration. Baseline serum phosphorus and FCM dose may be modifiable risk factors that should be considered for intervention in order to mitigate the risk of hypophosphatemia.

A Retrospective Chart Review to Determine Hypophosphatemia Incidence and Phosphorus Supplementation Requirements in Patients With Severe Thermal Cutaneous Injuries Receiving High-Volume Hemofiltration.

Patients with severe thermal injuries have increased metabolic demands necessitating frequent phosphate supplementation. Patients with acute renal failure may have less requirements, due to reduced elimination. However, patients being supported with renal replacement therapy have varying degree of requirements. Little published evidence depicts the incidence of hypophosphatemia and repletion requirements in patients with severe thermal injuries treated with high-volume hemofiltration (HVHF) and a high-flux membrane. The objective of this retrospective chart review was to determine the incidence of hypophosphatemia and characterize repletion requirements and response in this population. Enrolled patients had at least 20% TBSA thermal injuries and required continuous hemofiltration with prefilter replacement fluid doses ≥35 mL/kg IBW/hr. A randomly selected cohort without acute kidney injury (AKI) and matched based on age and extent of TBSA was used to compare phosphorus requirements over an initial 14-day period. Demographics, diet, and variables affecting phosphorus concentrations were collected. Sixteen patients were included in the retrospective HVHF group and 16 patients in a case-control cohort to better depict the impact of HVHF. The average age was 60.2 ± 15.1 years and median TBSA was 30% (23.4, 56.3) in the HVHF group, compared to 53.3 ± 16.4 years (P = .22) and TBSA 29% (26.4, 33.9; P = .73). All patients in the HVHF group were started on HVHF with a 1.6 m2 polyethersulfone membrane for AKI. As expected, the HVHF group exhibited statistically higher than normal baseline potassium and phosphorous laboratory values. The HVHF group experienced more days with hypophosphatemia (49.6 ± 12.4% vs 29.3 ± 16.3%, P = .012), despite 0.75 mmol/kg/day phosphorous supplementation (compared to 0.66 mmol/kg/day for the control group, P = .45). Patients with longer durations of HVHF therapy experienced increasing risk of hypophosphatemia, reaching 100% by the end of the study period. This study demonstrates severe thermally injured patients receiving HVHF for AKI are at increased risk for hypophosphatemia, and require high phosphate supplementation.

Early hypophosphatemia in critically ill children and the effect of parenteral nutrition: A secondary analysis of the PEPaNIC RCT.

BACKGROUND & AIMS: Hypophosphatemia during critical illness has been associated with adverse outcome. The reintroduction of enteral or parenteral nutrition, leading to refeeding hypophosphatemia (RFH), has been presented as potential risk factor. We investigated the occurrence of early RFH, its association with clinical outcome, and the impact of early parenteral nutrition (PN) on the development of early RFH in pediatric critical illness. METHODS: This is a secondary analysis of the PEPaNIC randomized controlled trial (N = 1440), which showed that withholding supplemental parenteral nutrition (PN) for 1 week (late-PN) in the pediatric intensive care unit (PICU) accelerated recovery and reduced new infections compared to early-PN (<24 h). Patients with renal replacement therapy or unavailable phosphate concentrations were excluded from this analysis. Early RFH was defined as serum/plasma phosphate <0.65 mmol/L and a drop of >0.16 mmol/L within 3 days of admission to the PICU. The association between baseline characteristics and early RFH, and the association of early RFH with clinical outcome were investigated using logistic and linear regression models, both uncorrected and corrected for possible confounders. To examine the impact of nutritional intake on phosphate concentrations, structural nested mean models with propensity score and censoring models were used. RESULTS: A total of 1247 patients were eligible (618 early-PN, 629 late-PN). Early RFH occurred in 40 patients (3%) in total, significantly more in the early-PN group (n = 31, within-group occurrence 5%) than in the late-PN-group (n = 9, within-group occurrence 1%, p < 0.001). Patients who were older (OR 1.14 (95% CI 1.08; 1.21) per year added, p < 0.001) and who had a higher Pediatric Risk of Mortality (PIM3) score had a higher risk of developing early RFH (OR 1.36 (95% CI 1.15; 1.59) per unit added, p < 0.001), whereas patients in the late-PN group had a lower risk of early RFH (OR 0.24 (95% CI 0.10; 0.49), p < 0.001). Early RFH was significantly associated with a 56% longer PICU stay (p = 0.003) and 42% longer hospital stay (p = 0.007), but not with new infections (OR 2.01 (95% CI 0.90; 4.30), p = 0.08) or length of mechanical ventilatory support (OR 1.05 (95% CI -3.92; 6.03), p = 0.68), when adjusted for possible confounders. Increase of parenteral nutrition intake (in % kcal of predicted resting energy expenditure) decreased phosphate concentrations (c = -0.002 (95% CI -0.002; -0.001). CONCLUSIONS: Early RFH occurred in 3% of critically ill children. Patients randomized to late-PN had a lower chance of developing early RFH, which may be explained by the more gradual build-up of nutrition. As early RFH might impact recovery, it is important to closely monitor phosphate concentrations in patients, especially of those at risk for early RFH.

Effect of hypophosphatemia on prognosis after spontaneous intracerebral hemorrhage: a retrospective study.

OBJECTIVE: Hypophosphatemia often occurs after spontaneous intracerebral hemorrhage, but the effect of hypophosphatemia on its prognosis is under debate. METHODS: Clinical data of patients with spontaneous intracerebral hemorrhage admitted to our neurosurgery department from January 2018 to June 2020 were retrospectively analyzed. The patients were divided into the hypophosphatemia group and the nonhypophosphatemia group according to the serum phosphorus test values obtained three times within 1 week after admission. The incidence of complications during hospitalization, 28-day mortality, and 6-month mRS score were compared between the two groups. The influence of low phosphorus in patients with hypophosphatemia on the 6-month mRS score was explored. RESULTS: A total of 133 patients were included, of which 85 had hypophosphatemia. Forty-two patients (21 in the hypophosphatemia group and 21 in the nonhypophosphatemia group) were enrolled after propensity score matching. There were no statistically significant differences in the incidence of complications during hospitalization, 28-day mortality, and 6-month mRS score between the two groups (P > 0.05). In 85 patients with hypophosphatemia, the minimum serum phosphorus was associated with the 6-month mRS score (B = - 3.153, 95% CI: - 5.842 ~ - 0.463, P = 0.022). The cutoff value of serumphosphorus for predicting 6-month mRS score was 0.505 mmol/l. CONCLUSION: Whether hypophosphatemia occurred during hospitalization in patients with spontaneous intracerebral hemorrhage showed no effect on the incidence of complications, 28-day mortality, and 6-month mRS score. A significant decrease in serum phosphorus during hospitalization (≤ 0.505 mmol/l) might correlate with a poor 6-month mRS score. Maintaining serum phosphorus stability after spontaneous intracerebral hemorrhage may improve prognosis.

The prevalence of hypophosphatemia and refeeding-related hypophosphatemia in hospitalized patients requiring parental nutrition: a retrospective study.

OBJECTIVE: Hypophosphatemia might cause respiratory and heart failure and even death. We aimed to evaluate risk factors for hypophosphatemia and refeeding-related hypophosphatemia in patients requiring parental nutrition (PN). METHODS: This was a single-center, retrospective study. Clinical parameters were obtained from medical records. Serum phosphate (inorganic phosphorus) was measured by photometric analysis. Hypophosphatemia was confirmed when serum phosphate level was less than 0.8 mmol/L (≈2.5 mg/dl). Refeeding related hypophosphatemia was confirmed if serum phosphate level had a decrease of 0.16 mmol/L or more from baseline and if the final assessment was below 0.65 mmol/L. RESULTS: A total number of 655 (426 men and 229 women, aged 62.8 ± 14.8 years) hospitalized patients requiring PN were included in the study, and 60.6% of them were patients with cancer. The average body mass index (BMI) was 21.1 ± 4.1 kg/m2 and the median of serum phosphate was 0.9 mmol/L (quartile range: 0.68 mmol/L, 1.11 mmol/L). The prevalence of hypophosphatemia was 37.6% (246/655). Older age (≥ 65 years vs. < 65 years), lower serum level of pre-albumin (< 160 mg/L vs. ≥ 160 mg/L), calcium (< 2.11 mmol/L vs. ≥ 2.11 mmol/L), and magnesium (< 0.75 mmol/L vs. ≥ 0.75 mmol/L) were associated with high risk of hypophosphatemia by multivariate logistic regression (OR ranged from 1.43 to 3.06, all p < 0.05). Refeeding related hypophosphatemia was 9.5% (16/168). Serum level of calcium at baseline was significantly lower in participants with refeeding related hypophosphatemia than those without it. Total calorie and nitrogen delivered during first week of PN period showed no obvious difference between patients with and without refeeding related hypophosphatemia. CONCLUSIONS: Hypophosphatemia is common (37.6%) in hospitalized patients requiring PN. Monitoring of serum level of phosphorus is necessary to facilitate early treatment of hypophosphatemia.

Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions.

BACKGROUND: In patients admitted to the Intensive Care Unit (ICU), Kidney Replacement Therapy (KRT) is an important risk factor for hypophosphataemia. However, studies addressing the development of hypophosphatemia during prolonged intermittent KRT modalities are lacking. Thus, we evaluated the incidence of hypophosphatemia during Sustained Low-Efficiency Dialysis (SLED) in ICU patients; we also examined the determinants of post-SLED serum phosphate level (s-P) and the relation between s-P and phosphate supplementation and ICU mortality. METHODS: We conducted a retrospective analysis on a cohort of critically ill patients with severe renal failure and KRT need, who underwent at least three consecutive SLED sessions at 24-72 h time intervals with daily monitoring of s-P concentration. SLED with Regional Citrate Anticoagulation (RCA) was performed with either conventional dialysis machines or continuous-KRT monitors and standard dialysis solutions. When deemed necessary by the attending physician, intravenous phosphate supplementation was provided by sodium glycerophosphate pentahydrate. We used mixed-effect models to examine the determinants of s-P and Cox proportional hazards regression models with time-varying covariates to examine the adjusted relation between s-P, intravenous phosphate supplementation and ICU mortality. RESULTS: We included 65 patients [mean age 68 years (SD 10.0); mean Acute Physiology and Chronic Health Evaluation II score 25 (range 9-40)] who underwent 195 SLED sessions. The mean s-P before the start of the first SLED session (baseline s-P) was 5.6 ± 2.1 mg/dL (range 1.5-12.3). Serum phosphate levels at the end of each SLED decreased with increasing age, SLED duration and number of SLED sessions (P < .05 for all). The frequency of hypophosphatemia increased after the first through the third SLED session (P = .012). Intravenous phosphate supplementation was scheduled after 12/45 (26.7%) SLED sessions complicated by hypophosphataemia. The overall ICU mortality was 23.1% (15/65). In Cox regression models, after adjusting for potential confounders and for current s-P, intravenous phosphate supplementation was associated with a decrease in ICU mortality [adjusted hazard ratio: 0.24 (95% confidence interval: 0.06 to 0.89; P = 0.033)]. CONCLUSIONS: Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality.

Hypophosphatemia Is Associated With Postoperative Morbidity After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: A Retrospective Study.

INTRODUCTION: Hypophosphatemia following surgery is associated with a higher rate of postoperative complications; however, the significance of postoperative hypophosphatemia after cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. METHODS: A prospectively maintained database was queried for all patients who underwent CRS/HIPEC for any histology at the Mount Sinai Health System. The perioperative serum phosphate levels, postoperative complications, and comorbidities were compared between patients with or without major complications. RESULTS: From 2007 to 2018, 327 patients underwent CRS/HIPEC. Most of the patients had low phosphate levels on postoperative day (POD) 2, reaching a median nadir of 2.3 mg/dL on POD 3. Patients with major complications had significantly lower levels of serum phosphate on POD 5-7 compared with patients without complications, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.4) versus 2.7 mg/dL, (IQR 2.3-3), P < 0.01. Hypophosphatemia on POD 5-7 was also more frequent in patients who developed an anastomotic leak, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.6) versus 2.8 mg/dL (IQR 2.2-3.2), P = 0.001. On multivariate analysis, the number of organs resected at surgery, diaphragm resection, postoperative intensive care unit stay, and serum phosphate level <2.4 mg/dL on POD 5-7 were independently associated with a major complication after CRS/HIPEC. CONCLUSIONS: Following CRS/HIPEC, POD 5-7 hypophosphatemia is associated with severe postoperative complications and anastomotic leak.

Association of Phosphate Containing Solutions with Incident Hypophosphatemia in Critically Ill Patients Requiring Continuous Renal Replacement Therapy.

BACKGROUND: Hypophosphatemia in critically ill patients is a common electrolyte disturbance associated with a myriad of adverse effects. Critically ill patients requiring continuous renal replacement therapy (CRRT) are at high risk of hypophosphatemia and often require phosphate supplementation during therapy. The aim of this study was to evaluate the association of phosphate versus non-phosphate containing CRRT solutions with incident hypophosphatemia in critically ill patients requiring CRRT. MATERIALS AND METHODS: This is a single-center, retrospective, cohort study at a tertiary academic medical center of 1,396 adult patients requiring CRRT during their intensive care unit stay comprising 7,529 (phosphate containing) and 4,821 (non-phosphate containing) cumulative days of CRRT. Multivariable logistic regression was used to model the primary outcome of hypophosphatemia during CRRT according to exposure to phosphate versus non-phosphate containing CRRT solutions. RESULTS: Incident hypophosphatemia during CRRT, serum phosphate <2.5 mg/dL or 0.81 mmol/L, was significantly higher in the non-phosphate versus phosphate containing solution group: 304/489 (62%) versus 175/853 (21%) (p < 0.001). Cumulative phosphate supplementation was also significantly higher in the non-phosphate versus phosphate containing solution group: 79 (IQR: 0-320) versus 0 (0-16) mmol (p < 0.001). Non-phosphate solutions were associated with an 8-fold increase in the incidence of hypophosphatemia (adjusted OR 8.05; 95% CI 5.77, 11.26; p < 0.001). DISCUSSION/CONCLUSIONS: The use of phosphate containing CRRT solutions was independently associated with reduced risk of incident hypophosphatemia and decreased phosphate supplementation during CRRT. Interventional studies to confirm these findings are needed.

Hypophosphatemia in critically ill pediatric patients receiving enteral and oral nutrition.

BACKGROUND: Hypophosphatemia(HP) is related to several comorbidities in pediatric intensive care units (PICUs). This study aimed to evaluate the incidence of HP in severely ill pediatric patients receiving oral and/or enteral nutrition. The secondary objectives were to investigate the association between HP and the inflammatory state, PICU length of stay, severity, mortality, nutrition status, and protein, energy, calcium, vitamin D, and phosphate intake. METHODS: A prospective, observational cohort study was conducted in a PICU of a quaternary hospital. Participants aged between 28 days and 14 years were included. Anthropometric and laboratory assessments were performed ≤72 h after PICU admission and repeated after 7 days for three consecutive times. Energy, protein, calcium, phosphate, and vitamin D intake per day of hospitalization were recorded individually. The Pediatric Index of Mortality 2 (PIM2) was used to determine each patient's severity score. RESULTS: A total of 103 participants were included in the study. Hypophosphatemic events ranged from 27.2% to 37.5% among the assessments. HP was associated with high C-reactive protein levels (P = .012) and lower energy adequacy (P = .037). Serum phosphorus was inversely correlated (weak correlation) with PIM2 (P = .017). CONCLUSION: HP is common in critically ill pediatric patients, even when they are not receiving parenteral nutrition. It is necessary to monitor serum phosphorus levels and consider the possibility of early replacement, especially in patients showing high levels of inflammation. In addition to inflammation itself, low energy intake and illness severity were related to HP.

Hypophosphatemia after high-dose intravenous iron treatment in patients with inflammatory bowel disease: Mechanisms and possible clinical impact.

BACKGROUND: High-dose intravenous iron is an effective treatment option for iron deficiency (ID) or ID anaemia (IDA) in inflammatory bowel disease (IBD). However, treatment with ferric carboxymaltose (FCM) has been associated with the development of hypophosphatemia. AIM: To investigate mechanisms behind the development of hypophosphatemia after intravenous iron treatment, and disclose symptoms and clinical manifestations related to hypophosphatemia short-term. METHODS: A prospective observational study of adult IBD patients with ID or IDA was conducted between February 1, 2017 and July 1, 2018 at two separate university hospitals in the southeast region of Norway. Patients received one dose of 1000 mg of either FCM or ferric derisomaltose (FDI) and were followed for an observation period of at least 7 wk. Blood and urine samples were collected for relevant analyses at baseline, week 2 and at week 6. Clinical symptoms were assessed at the same timepoints using a respiratory function test, a visual analogue scale, and a health-related quality of life questionnaire. RESULTS: A total of 106 patients was available for analysis in this study. The FCM treatment group consisted of 52 patients and hypophosphatemia was present in 72.5% of the patients at week 2, and in 21.6% at week 6. In comparison, the FDI treatment group consisted of 54 patients and 11.3% of the patients had hypophosphatemia at week 2, and 3.7% at week 6. The difference in incidence was highly significant at both week 2 and 6 (P < 0.001 and P < 0.013, respectively). We observed a significantly higher mean concentration of intact fibroblast growth factor 23 (P < 0.001), a significant rise in mean urine fractional excretion of phosphate (P = 0.004), a significant decrease of 1,25-dihydroxyvitamin D (P < 0.001) and of ionised calcium levels (P < 0.012) in the FCM-treated patients compared with patients who received FDI. No clinical symptoms could with certainty be related to hypophosphatemia, since neither the respiratory function test, SF-36 (36-item short form health survey) or the visual analogue scale scores resulted in significant differences between patients who developed hypophosphatemia or not. CONCLUSION: Fibroblast growth factor 23 has a key role in FCM induced hypophosphatemia, probably by inducing loss of phosphate in the urine. Short-term clinical impact of hypophosphatemia was not demonstrated.

Hypophosphatemia in a Specialized Intestinal Failure Unit: An Observational Cohort Study.

BACKGROUND: Patients with intestinal failure (IF) are prone to hypophosphatemia and shifts in magnesium and potassium levels. Although these shifts are often attributed to refeeding syndrome (RFS), the incidence of electrolyte shifts among patients with IF is unknown. We evaluated the occurrence of hypophosphatemia and other electrolyte shifts according to the functional and pathophysiological IF classifications. METHODS: We consecutively included all patients' first admission to an IF unit from 2013 to 2017. Electrolyte shifts were defined as severe hypophosphatemia <0.6 mmol/L (mM) or any 2 other shifts below reference range, comprising hypomagnesemia <0.75 mM, hypophosphatemia <0.8 mM, or hypokalemia <3.5 mM. Outcomes included length of stay, central line-associated bloodstream infection, and other infections. Mortality was evaluated 6 months after discharge. RESULTS: Of 236 patients with IF, electrolyte shifts occurred in 99 (42%), and 127 (54%) of these patients received intravenous supplementation with either phosphate, magnesium, or potassium. In patients who started parenteral nutrition, up to 62% of early-onset shifts (<5 days) related to refeeding, and up to 63% of late-onset shifts (≥5 days) could be ascribed to infections. Derangements occurred in 7 (18%) with type 1 IF, 53 (43%) with type 2 IF, and 39 (53%) readmitted patients with type 3 IF. Of 133 patients with IF secondary to short-bowel syndrome, 65 (49%) developed shifts. CONCLUSION: In patients with IF, electrolyte shifts are frequent but not always due to RFS. Electrolyte shifts are common in patients with type 2 and those readmitted with type 3 IF.

Diets with high carbohydrate contents were associated with refeeding hypophosphatemia: A retrospective study in Japanese inpatients with anorexia nervosa.

OBJECTIVE: Refeeding hypophosphatemia (RH) is a potentially fatal complication in patients with anorexia nervosa (AN), and its dietary preventive strategy is not well established. We aimed to examine the association between carbohydrate content in the diet and the occurrence of RH in inpatients with AN via retrospective medical chart review. METHOD: We performed a chart review to collect data of patients with AN hospitalized at the Department of Psychosomatic Medicine of the University of Tokyo Hospital between April 1, 2012, and February 29, 2020. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point of the percentage of carbohydrate content in the diet for the occurrence of RH. Multivariate logistic regression analysis was performed with occurrence of RH as the dependent variable and the carbohydrate content of more than the identified cutoff point as the independent variable adjusting for the risk factors for RH. RESULTS: The percentage of carbohydrate content that is higher than the cutoff point obtained from the ROC analysis (58.4%) was significantly associated with the occurrence of RH, even after adjusting for variables associated with RH in univariate logistic regression analysis (age and body mass index) as well as the average daily calorie intake (odds ratio, 5.37; 95% confidence interval, 1.60-18.1; p = .0066). DISCUSSION: We identified that diets with higher carbohydrate contents were associated with RH in inpatients with AN, even after adjusting for known risk factors. Our findings may promote the development of dietary preventive strategies against RH in inpatients with AN.

Prevalência de hipofosfatemia e risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva / Prevalence of hypophosphatemia and risk of refeeding syndrome in elderly patients admitted to an intensive care unit

Introdução: A presença de hipofosfatemia é fortemente relacionada à ocorrência de síndrome de realimentação em pacientes críticos, na qual um dos principais grupos de risco é a população idosa. Objetivos: Avaliar a prevalência de hipofosfatemia e o risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva. Métodos: Estudo observacional prospectivo, realizado numa unidade de terapia intensiva com pacientes idosos de ambos os sexos e em uso de terapia nutricional enteral. Foram coletados dados demográficos, clínicos e exames bioquímicos, e realizadas triagem e avaliação nutricional. As necessidades nutricionais foram calculadas e adotou-se o ponto de corte de 90% para estabelecer a adequação da oferta calórica. Para avaliar o risco e a ocorrência de síndrome de realimentação, foram utilizados os critérios propostos pelo grupo NICE. A análise estatística foi realizada com o auxílio do programa SPSS 13.0, com um intervalo de confiança (IC) de 95%. Resultados: Foram estudados 44 pacientes, dos quais 34,1% estavam em magreza; 86,4% dos pacientes iniciaram a terapia nutricional enteral em até 48 horas, com 43,2% de adequação calórica em até 72 horas. A hipofosfatemia foi encontrada em 9,1% dos pacientes na admissão e em 29,5% após o início da dieta. Com isso, 88,6% dos pacientes apresentaram algum risco para desenvolver síndrome de realimentação e 40,9% deles manifestaram a síndrome. Conclusão: Foi identificada elevada prevalência de hipofosfatemia após o início da terapia nutricional. Além disso, o risco de desenvolver síndrome de realimentação foi elevado e sua manifestação se assemelha aos dados encontrados na literatura. (AU)

Introduction: The presence of hypophosphatemia is strongly related to the occurrence of refeeding syndrome in critically ill patients, in which one of the main risk groups is the elderly population. Objectives: To assess the prevalence of hypophosphatemia and the risk of refeeding syndrome in elderly patients admitted to an intensive care unit. Methods: Prospective observational study carried out in an intensive care unit with elderly patients of both genders using enteral nutritional therapy. Demographic, clinical and biochemical data were collected, and nutritional screening and assessment were performed. The energy and nutrient requirements were calculated and a cutoff point of 90% was adopted to establish the adequacy of the caloric supply. To assess the risk and occurrence of refeeding syndrome, the criteria proposed by the NICE group were used. Statistical analyses were performed using the SPSS 13.0 program, with a 95% confidence interval (CI). Results: 44 patients were studied, of which 34.1% were malnourished; 86.4% of patients started enteral nutritional therapy within 48 hours, with 43.2% of caloric adequacy within 72 hours. Hypophosphatemia was found in 9.1% of patients on admission and in 29.5% after starting the diet. Thus, 88.6% of patients had some risk of developing the refeeding syndrome and 40.9% of them manifested the syndrome. Conclusion: A high prevalence of hypophosphatemia was identified after starting nutritional therapy. In addition, the risk of developing refeeding syndrome was high and its manifestation is similar to data found in the literature. (AU)

Ferric carboxymaltose (Ferinject®) associated hypophosphataemia: case report illustrating the need for increased awareness to minimise incidence and risk.

Ferric carboxymaltose (Ferinject®) is an infusion administered for the treatment of iron deficiency anaemia. A number of previous case reports have shown the occurrence of hypophosphataemia after Ferinject® treatment, supposedly managed though high dose phosphate therapy. This case report highlights the risk associated with, and futility of, managing this adverse effect through high dose phosphate infusion. A review of the available literature suggests that if hypophosphataemia develops as a result of Ferinject®, through upregulation of the renal protein Fibroblast Growth Factor-23, it cannot be readily reversed and on average persists for circa 50 days. Acute medical units should be aware of this - likely underreported - adverse effect, and avoid treating these hypophosphataemic patients with high dose phosphate since it can compound symptoms.

Refeeding syndrome in small ruminants receiving parenteral nutrition.

BACKGROUND: Small ruminants presented to tertiary care facilities commonly suffer from severe protein-calorie malnutrition. Some of these patients require parenteral nutrition (PN; amino acids and dextrose with or without lipids) during hospitalization. Refeeding syndrome, a potentially fatal shift of electrolytes seen in malnourished patients during refeeding, may occur. OBJECTIVE: (a) To report the prevalence of refeeding syndrome in small ruminants receiving PN and (b) to determine risk factors for the development of refeeding syndrome. ANIMALS: Hospitalized small ruminants (n = 20) that received PN from 2010 to 2018 and that had serial (≥2) monitoring of serum electrolyte concentrations after initiation of PN. METHODS: Retrospective case series. Refeeding syndrome was defined as the presence of at least 2 of the following electrolyte abnormalities after initiation of PN: hypophosphatemia, hypokalemia, hypomagnesemia, or some combination of these. Data was analyzed using Fisher's exact test, followed by univariate logistic regression. RESULTS: Eleven of 20 (55%) animals met the definition of refeeding syndrome. Mean minimum serum phosphorus concentration in animals with refeeding syndrome was 1.96 ± 0.69 mg/dL (reference range, 4.2-7.6 mg/dL). Eleven of 20 animals survived to discharge. Survival rate did not differ significantly between refeeding cases (4/11, 36.3%) and nonrefeeding cases (7/9, 77.8%; P = .09). Mean serum phosphorus concentration was significantly lower in nonsurvivors than in survivors (1.88 ± 0.10 mg/dL vs 4.32 ± 0.70 mg/dL, P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE: We report the prevalence of refeeding syndrome in small ruminants receiving PN. Clinicians should anticipate refeeding syndrome after initiation of PN and consider pre-emptive supplementation with phosphorus, potassium, magnesium, or some combination of these.

High Risk of Hypophosphatemia in Patients with Previous Bariatric Surgery Receiving Ferric Carboxymaltose: A Prospective Cohort Study.

BACKGROUND: Iron deficiency is a common finding in patients with previous bariatric surgery, and parenteral supplementation is frequently required. Ferric carboxymaltose (FCM) is among the preferred compounds used but may be associated with new-onset hypophosphatemia. This study was undertaken to study the prevalence of hypophosphatemia following FCM in patients with previous bariatric surgery, a population that may be at particular risk due to highly prevalent secondary hyperparathyroidism. METHODS: Patients with previous bariatric surgery and iron depletion scheduled for FCM infusion were prospectively studied before and one week after FCM application. The primary endpoint was new-onset hypophosphatemia. Patients were followed until plasma phosphate had normalized without replacement. RESULTS: Fifty-two patients (40 females) following Roux-en-Y gastric bypass (n = 50) or sleeve gastrectomy (n = 2), with a median age of 46 years (range 22-68) and a BMI of 32.2 kg/m2 (27.5-37.3), were analyzed. Fifteen patients (29%) developed new-onset hypophosphatemia, with 11 (21%) requiring oral phosphate supplementation for a median duration of 14 days (14-25). The plasma phosphate decreased by 0.3 mmol/l (-0.5--0.2; p < 0.001) secondary to a 56% increase in the fractional urinary phosphate excretion (p < 0.001). This was associated with a significant increase in serum intact FGF23 (+30%; p < 0.001) and a decrease in serum 1,25(OH)2 vitamin D3 concentrations (-37.6%; p < 0.001). CONCLUSION: Patients with previous bariatric surgery receiving FCM are at considerable risk of developing significant hypophosphatemia secondary to increased renal phosphate wasting through a mechanism involving FGF23. Monitoring plasma phosphate should be considered following FCM in patients with previous bariatric surgery. CLINICAL TRIAL REGISTRATION: ISRCTN registry, ISRCTN12291677, https://www.isrctn.com.