Phosphaturic mesenchymal tumor-induced bilateral osteomalacia femoral neck fractures: a case report.

Phosphaturic mesenchymal tumors (PMT) are rare and distinctive tumors that typically result in paraneoplastic syndrome known as tumor-induced osteomalacia (TIO). We report a case of bilateral osteoporotic femoral neck fracture caused by PMT. PMT was surgically resected, followed by sequential treatment of bilateral femoral neck fractures with total hip arthroplasty (THA). A 49-year-old perimenopausal woman experienced consistent bone pain with limb weakness persisting for over 2 years. Initially, she was diagnosed with early osteonecrosis of the femoral head and received nonsurgical treatment. However, from 2020 to 2022, her pain extended to the bilateral shoulders and knees with increased intensity. She had no positive family history or any other genetic diseases, and her menstrual cycles were regular. Physical examination revealed tenderness at the midpoints of the bilateral groin and restricted bilateral hip range of motion, with grade 3/5 muscle strength in both lower extremities. Laboratory findings revealed moderate anemia (hemoglobin 66 g/L), leukopenia (2.70 × 109/L), neutropenia (1.28 × 109/L), hypophosphatemia (0.36 mmol/L), high alkaline phosphatase activity (308.00 U/L), and normal serum calcium (2.22 mmol/L). After surgery, additional examinations were performed to explore the cause of hypophosphatemic osteomalacia. After definitive diagnosis, the patient underwent tumor resection via T11 laminectomy on August 6, 2022. Six months after the second THA, the patient regained normal gait with satisfactory hip movement function without recurrence of PMT-associated osteomalacia or prosthesis loosening. By providing detailed clinical data and a diagnostic and treatment approach, we aimed to improve the clinical understanding of femoral neck fractures caused by TIO.

[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.

Tumour-induced osteomalacia: the long road to diagnosis and recovery.

Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated. 68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.

Nomogram for predicting early hypophosphatemia in term infants.

BACKGROUND: Physiological processes rely on phosphate, which is an essential component of adenosine triphosphate (ATP). Hypophosphatasia can affect nearly every organ system in the body. It is crucial to monitor newborns with risk factors for hypophosphatemia and provide them with the proper supplements. We aimed to evaluate the risk factors and develop a nomogram for early hypophosphatemia in term infants. METHODS: We conducted a retrospective study involving 416 term infants measured serum phosphorus within three days of birth. The study included 82 term infants with hypophosphatemia (HP group) and 334 term infants without hypophosphatemia (NHP group). We collected data on the characteristics of mothers, newborn babies, and childbirth. Furthermore, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for hypophosphatemia in term infants, and a nomogram was developed and validated based on the final independent risk factors. RESULTS: According to our analysis, the multivariate logistic regression analysis showed that male, maternal diabetes, cesarean delivery, lower serum magnesium, and lower birth weight were independent risk factors for early hypophosphatemia in term infants. In addition, the C-index of the developed nomogram was 0.732 (95% CI = 0.668-0.796). Moreover, the calibration curve indicated good consistency between the hypophosphatemia diagnosis and the predicted probability, and a decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSIONS: The analysis revealed that we successfully developed and validated a nomogram for predicting early hypophosphatemia in term infants.

Hypophosphatemia after Start of Medical Nutrition Therapy Indicates Early Refeeding Syndrome and Increased Electrolyte Requirements in Critically Ill Patients but Has No Impact on Short-Term Survival.

Refeeding syndrome (RFS) is a potentially life-threatening complication in malnourished (critically ill) patients. The presence of various accepted RFS definitions and the inclusion of heterogeneous patient populations in the literature has led to discrepancies in reported incidence rates in patients requiring treatment at an intensive care unit (ICU). We conducted a prospective observational study from 2010 to 2013 to assess the RFS incidence and clinical characteristics among medical ICU patients at a large tertiary center. RFS was defined as a decrease of more than 0.16 mmol/L serum phosphate to values below 0.65 mmol/L within seven days after the start of medical nutrition therapy or pre-existing serum phosphate levels below 0.65 mmol/L. Overall, 195 medical patients admitted to the ICU were included. RFS was recorded in 92 patients (47.18%). The presence of RFS indicated significantly altered phosphate and potassium levels and was accompanied by significantly more electrolyte substitutions (phosphate, potassium, and magnesium). No differences in fluid balance, energy delivery, and insulin requirements were detected. The presence of RFS had no impact on ICU length of stay and ICU mortality. Screening for RFS using simple diagnostic criteria based on serum phosphate levels identified critically ill patients with an increased demand for electrolyte substitutions. Therefore, stringent monitoring of electrolyte levels is indicated to prevent life-threatening complications.

An infant developing hypercalcemia and hypophosphatemia due to the use of exclusively almond milk.

OBJECTIVES: Plant-based milk alternatives are increasingly utilized in children with cow milk allergy, lactose intolerance, and personal preference. However, notable differences exist in mineral content between cow milk and plant-based alternatives. Almond milk, in particular, varies in mineral and caloric content across different brands. This case report highlights a toddler who developed hypercalcemia and hypophosphatemia attributed to almond milk consumption. CASE PRESENTATION: A fourteen-month-old girl with a history of biliary atresia underwent liver transplant at seven months of age. She was exclusively consuming almond milk for two months prior to presentation. She was admitted to the hospital for severe hypercalcemia (14.6 mg/dL) and hypophosphatemia (1.6 mg/dL). She had elevated random urine calcium to creatinine ratio (2.56 mg/g) and low urine phosphorus to creatinine ratio (<0.44 mg/g) were noted. Parathyroid hormone (PTH) level was appropriately suppressed (<6 pg/mL), while 1,25 dihydroxyvitamin D level was slightly elevated at 88 pg/mL. Initial management included intravenous fluids, followed by a switch to a formula with higher phosphorus and lower calcium concentrations. The patient was discharged after six days with normalized calcium and phosphorus levels, which remained within the normal range. CONCLUSIONS: Although plant-derived milk serves as a viable alternative to cow milk, careful consideration of mineral content, particularly in infants and toddlers, is imperative. Sole reliance on almond milk for nutritional needs in this population is not recommended. Caregivers should be informed about the potential risks associated with almond milk consumption in infants and toddlers.

Phosphaturic mesenchymal tumor: Clinicopathological features with outcomes in 10 patients with review of literature.

BACKGROUND: Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal tumors, associated with long-standing, non-specific but often debilitating symptoms in the affected patients. These tumors display characteristic histopathological features and in case, identified timely, can be a boon for patients, given an excision is completely curative. AIMS: To evaluate the clinical and histopathological features of 10 PMTs, diagnosed at our institution, along with clinical outcomes in those patients. MATERIALS AND METHODS: This was a retrospective study, wherein 10 PMTs, diagnosed from January 2013 to July 2022, were included. RESULTS: The average age at the time of diagnosis was 40 years with an M:F ratio of 4:1. Clinical features included lumps, weakness, bone pain, difficulty in moving and walking, and pathologic fractures. The biochemical analysis showed normal serum calcium levels (average = 9.5 mg/dL), with low serum phosphorus (average = 2.2 mg/dL) and raised serum fibroblast growth factor 23 (FGF23) levels, in all the cases, wherever available. On histopathology, all tumors showed cells arranged in a hemangiopericytomatous pattern, including oval to short spindle forms. Multinucleate giant cells were present in nine tumors, and characteristic "grungy calcifications" was observed in eight tumors. Prominent pseudo cystic spaces were seen in eight tumors. A significant number of mitotic figures and tumor necrosis were not seen in any tumor. In five cases where follow-up was available, there was complete resolution of symptoms post-resection with no recurrence or metastasis. All those patients were free of disease until the last follow-up. CONCLUSION: This constitutes the first largest comprehensive study on these rare tumors from our country. PMTs can be diagnosed based on certain histopathological features and correlation with clinicoradiological and biochemical findings. These are invariably benign neoplasms. Patients are relieved of their debilitating symptoms after adequate surgical tumor resection. Therefore, their correct and timely diagnosis is crucial.

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.

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.

The pathophysiology of hypophosphatemia.

After identification of fibroblast growth factor (FGF) 23 as the pivotal regulator of chronic serum inorganic phosphate (Pi) levels, the etiology of disorders causing hypophosphatemic rickets/osteomalacia has been clarified, and measurement of intact FGF23 serves as a potent tool for differential diagnosis of chronic hypophosphatemia. Additionally, measurement of bone-specific alkaline phosphatase (BAP) is recommended to differentiate acute and subacute hypophosphatemia from chronic hypophosphatemia. This article divides the etiology of chronic hypophosphatemia into 4 groups: A. FGF23 related, B. primary tubular dysfunction, C. disturbance of vitamin D metabolism, and D. parathyroid hormone 1 receptor (PTH1R) mediated. Each group is further divided into its inherited form and acquired form. Topics for each group are described, including "ectopic FGF23 syndrome," "alcohol consumption-induced FGF23-related hypophosphatemia," "anti-mitochondrial antibody associated hypophosphatemia," and "vitamin D-dependent rickets type 3." Finally, a flowchart for differential diagnosis of chronic hypophosphatemia is introduced.

Hypophosphatemia as a Predictor of Clinical Outcomes in Acute Pancreatitis: A Retrospective Study.

OBJECTIVE: Phosphate is crucial for cellular repair after injury and may be important in recovery following acute pancreatitis (AP). This study aimed to evaluate the association between hypophosphatemia and severity of AP. METHODS: Patients admitted with AP between 2014-2018 were identified and their records were retrospectively reviewed. Pancreatitis severity was defined using the modified Atlanta Criteria. Hypophosphatemia was defined as phosphate <2 mg/dL and was assessed at three time points: within one day, within two days, at any time during admission. The proportion of patients who developed severe AP was compared between patients with and without hypophosphatemia. RESULTS: Of 312 patients, 30.1% (n = 94) developed severe AP. Hypophosphatemia occurred in 25.0% overall, within one day in 19.7%, and within two days in 20.0%. A higher proportion of patients with hypophosphatemia developed severe AP (overall: 47.4% vs. 24.4%, P < 0.001; one day: 47.4% vs. 23.9%, P = 0.004; two days: 42.9% vs. 24.5%, P = 0.01). Patients with hypophosphatemia within one day were also more likely to have ICU admission ( P < 0.001) and longer length of stay ( P < 0.001). CONCLUSIONS: Early hypophosphatemia during an admission for AP was associated with increased AP severity, ICU admission, and longer length of stay.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

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.

Phosphate: An underrated component of primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a systemic disease that affects all the systems of the body, specifically the bones and the kidneys. Its main action is on calcium homeostasis. It tries to preserve the body's calcium level at the cost of phosphate. The criteria for surgery in asymptomatic PHPT patients revolve around raised serum calcium levels, renal dysfunction or nephrolithiasis, and bone health. It does not take into account the serum phosphate levels. Depending on the serum level, Hypophosphatemia is divided into mild, moderate, and severe categories. In PHPT, several studies have suggested that asymptomatic PHPT patients with moderate hypophosphatemia may warrant surgical intervention. Treatment of hypophosphatemia in PHPT is based upon the degree of hypophosphatemia, and treatment is given according to that oral or intravenous route; after surgical and medical treatment of PHPT, phosphate levels gradually normalized. But even after these considerations, phosphate levels in PHPT are not given much importance.

[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

Impact of Intensity of Continuous Renal Replacement Therapy on Duration of Ventilation in Critically Ill Patients: A Secondary Analysis of the RENAL Trial.

INTRODUCTION: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. METHODS: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. RESULTS: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5-16] vs. 8 [5-15] days; adjusted median difference, 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). CONCLUSIONS: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.