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.

[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.

[Rare causes of Hypophosphatemia: diagnostic approach]. / Hypophosphatémies de causes rares : approche diagnostique.

Hypophosphatemia is common and may be overlooked due to its asymptomatic nature or non-specific symptoms. Two main mechanisms are at its origin: a shift towards the intracellular sector and an increase in urinary phosphate excretion. A measurement of the urinary phosphate reabsorption threshold allows a diagnostic orientation. Alongside common forms of parathyroid hormone-dependent hypophosphatemia, one should not ignore rare FGF23-mediated forms, in particular X-linked hypophosphatemic rickets. The treatment, above all etiological, also includes the administration of phosphate and, in the event of an excess of FGF23, supplementation with calcitriol. In cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets, the use of burosumab, an anti-FGF23 antibody, must be considered.

L'hypophosphatémie est fréquente. Pourtant, elle peut parfois être méconnue de par son caractère asymptomatique ou ses symptômes non spécifiques. Deux grands mécanismes sont à son origine : un shift vers le secteur intracellulaire et une augmentation de l'excrétion urinaire de phosphate. Une mesure du seuil de réabsorption urinaire de phosphate permet une orientation diagnostique. À côté de formes communes d'hypophosphatémies parathormone-dépendantes, il ne faut pas méconnaître des formes rares FGF23 médiées, en particulier le rachitisme hypophosphatémique lié à l'X. Le traitement, avant tout étiologique comporte aussi l'administration de phosphate et lors d'un excès de FGF23, une supplémentation en calcitriol. En cas d'ostéomalacie oncogénique et de rachitisme hypophosphatémique lié à l'X, l'emploi de burosumab, anticorps anti-FGF23, doit être considéré.

Reflections on TRP and TP/GFR in the definition of renal phosphate loss: conceptual review.

BACKGROUND: Fractional tubular reabsorption of phosphate (TRP) has been used for over 60 years to establish the existence of renal phosphate loss. It is a parameter of corrected volume per decilitre of glomerular filtration rate (GFR). Later, a mass parameter per dl GFR called TP/GFR (tubular PO4 reabsorption per dl GFR) was devised which some authors have sought to substitute for TRP. The aim of the present work is to attempt to demonstrate that TRP and TP/GFR are similar parameters and, in certain aspects, TRP is more effective for diagnosis. METHODS: Data were gathered on the metabolism of phosphate corresponding to a group of healthy children without hypophosphatemia (n = 47), a group of patients with idiopathic hypercalciuria (n = 27), and ten patients diagnosed with X-linked hypophosphatemia (XLH). The TRP, the TP/GFR, and the percent tubular reabsorption of phosphate were calculated. RESULTS: All the patients with XLH presented TRP values lower than 95 ml/dl GFR and of TP/GFR equal to or lower than 2.8 mg/dl GFR. In the total sample, a direct correlation was observed between TRP and TP/GFR (r = 0.65; p = 0.01). The TRP and the percent tubular reabsorption of phosphate values were the same in the three groups (r = 1; p = 0.01). CONCLUSIONS: TRP and TP/GFR are similar parameters. TRP is more effective than TP/GFR given that in renal hypophosphatemia it is always below 95% and above 95% in reduced phosphatemia and normal kidney proximal tubular function. There is no solid reason for using TP/GFR rather than TRP. A higher resolution version of the Graphical abstract is available as Supplementary information.

Fanconi Syndrome Associated with Long-term Treatment with Zoledronate.

Intravenous bisphosphonate therapy is used to prevent fractures in the management of bone metastasis. However, it may induce renal damage. We herein report an 81-year-old woman with Fanconi syndrome and osteomalacia who had been diagnosed with metastatic breast cancer and received treatment with zolendronate for over 5 years. Her bone markers normalized after switching zolendronate to denosmab and starting vitamin D and mineral supplementation. This case shows that chronic renal damage induced by zolendronate can cause osteomalacia. In patients with intravenous zolendronate therapy, close monitoring of renal and bone markers is needed, even under long-term therapy.

Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome.

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is caused by somatic mosaic NRAS variants and characterized by melanocytic/sebaceous naevi, eye, and brain malformations, and FGF23-mediated hypophosphatemic rickets. The MEK inhibitor Trametinib, acting on the RAS/MAPK pathway, is a candidate for CSHS therapy. A 4-year-old boy with seborrheic nevus, eye choristoma, multiple hamartomas, brain malformation, pleural lymphangioma and chylothorax developed severe hypophosphatemic rickets unresponsive to phosphate supplementation. The c.182A > G;p.(Gln61Arg) somatic NRAS variant found in DNA from nevus biopsy allowed diagnosing CSHS. We administered Trametinib for 15 months investigating the transcriptional effects at different time points by whole blood RNA-seq. Treatment resulted in prompt normalization of phosphatemia and phosphaturia, catch-up growth, chylothorax regression, improvement of bone mineral density, reduction of epidermal nevus and hamartomas. Global RNA sequencing on peripheral blood mononucleate cells showed transcriptional changes under MEK inhibition consisting in a strong sustained downregulation of signatures related to RAS/MAPK, PI3 kinase, WNT and YAP/TAZ pathways, reverting previously defined transcriptomic signatures. CSHS was effectively treated with a MEK inhibitor with almost complete recovery of rickets and partial regression of the phenotype. We identified "core" genes modulated by MEK inhibition potentially serving as surrogate markers of Trametinib action.

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.

Hungry Bone Syndrome After Living Donor Liver Transplant for Biliary Atresia.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

Parenteral iron therapy and phosphorus homeostasis: A review.

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

Hypophosphatemia as an Early Metabolic Bone Disease Marker in Extremely Low-Birth-Weight Infants After Prolonged Parenteral Nutrition Exposure.

BACKGROUND: Early metabolic bone disease (MBD) detection is important in preterm infants to decrease long-term consequence. We aim to explore the early MBD biochemical marker in extremely low-birth-weight (ELBW) infants. METHODS: Retrospective cohort study of 95 preterm infants born in a tertiary care-level neonatal intensive care unit between January 2015 and June 2018, with birth weight <1000 g. Thirty-five infants were "nothing by mouth" for >14 days and categorized as the high-risk group; the remaining 60 were categorized as the control group. Mineral intake in the first 14 days and the trend of serum calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were compared in both groups. RESULTS: The Ca and P supplementation in the first 2 weeks of life were inadequate in both groups. Compared with the control group, significantly lower serum P (mg/dL) levels were noted in the high-risk group on weeks 2 (3.65 ± 1.2 vs 4.67 ± 1.45; P < .001), 4 (3.21 ± 0.95 vs 5.83 ± 1.18; P < .0001), and 6 (3.94 ± 1.1 vs 6.22 ± 0.78; P <.0001). There was no significant difference in the serum Ca level, and significantly higher ALP (U/L) levels were found up until 2 months of life in the high-risk group (458.36 ± 189.02 vs 335.7 ± 111.51; P < .014). CONCLUSION: Hypophosphatemia developed as early as 2 weeks old in high-risk preterm infants because of inadequate supplementation. Neither the serum Ca or ALP levels were affected. Thus, the routine monitoring of serum P level should be started 2 weeks after birth for early MBD detection in extremely ELBW infants.

Normal-range emergency department serum phosphorus levels and all-cause mortality.

PURPOSE OF THE STUDY: Hypophosphataemia and hyperphosphataemia are frequently encountered in hospitalised patients and are associated with significant clinical consequences. However, the prognostic value of normal-range phosphorus levels on all-cause mortality and hospitalisations is not well established. Therefore, we examined the association between normal-range phosphorus levels, all-cause mortality and hospitalisations in patients presenting to the emergency department of a tertiary medical centre in Israel. STUDY DESIGN: A retrospective analysis of patients presenting to the Chaim Sheba Medical Center emergency department between 2012 and 2018. The cohort was divided into quartiles based on emergency department phosphorus levels: 'very-low-normal' (p ≥ 2 mg/dL and p ≤ 2.49 mg/dL), 'low-normal' (p ≥ 2.5 mg/dL and p ≤ 2.99 mg/dL), 'high-normal' (p≥  3 mg/dL and p≤3.49 mg/dL) and 'very-high-normal' (p ≥  3.5 mg/dL and p ≤ 4 mg/dL). We analysed the association between emergency department phosphorus levels, hospitalisation rate and 30-day and 90-day all-cause mortality. RESULTS: Our final analysis included 223 854 patients with normal-range phosphorus levels. Patients with 'very-low-normal' phosphorus levels had the highest mortality rate. Compared with patients with 'high-normal' phosphorus levels, patients with 'very-low-normal' levels had increased 30-day all-cause mortality (OR 1.3, 95% CI 1.1 to 1.4, p<0.001), and increased 90-day all-cause mortality (OR 1.2, 95% CI 1.1 to 1.3, p<0.001). Lower serum phosphorus levels were also associated with a higher hospitalisation rate, both for the internal medicine and general surgery wards (p<0.001). CONCLUSIONS: Lower phosphorus levels, within the normal range, are associated with higher 30-day and 90-day all-cause mortality and hospitalisation rate.

Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus (R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution (R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

Predictors of Hypophosphatemia and Outcomes during Continuous Renal Replacement Therapy.

INTRODUCTION: Hypophosphatemia occurs in up to 80% of patients undergoing continuous renal replacement therapy (CRRT) and has been associated with poor outcomes. Whether preemptive phosphate supplementation is warranted in select patients has not been adequately explored. This single-center, retrospective cohort study evaluates predictors of hypophosphatemia and characterizes treatment approaches in adult patients undergoing at least 12 h of CRRT. METHODS: Patients were divided into 2 groups based on the presence or absence of hypophosphatemia as defined by serum phosphorus <2.5 mg/dL. Select laboratory values at baseline and during CRRT, medications and nutritional sources affecting phosphorus, and CRRT parameters were compared. Patient outcomes including resolution of acute kidney injury (AKI), freedom from renal replacement therapy at hospital discharge, duration of intensive care unit (ICU) and hospital stay, duration of mechanical ventilation, and ICU mortality were evaluated. RESULTS: Seventy-two patients were included. The group was 43% female and 51% African American. CRRT was ordered for AKI in 83% and for end-stage renal disease in 15%. Hypophosphatemia occurred in 45 patients (63%). Mean time to development of hypophosphatemia was 34 ± 22 h. Patients who developed hypophosphatemia received a longer duration of CRRT (p = 0.001), were more likely to have a diet ordered (p = 0.005), less likely to have received calcium infusions (p = 0.045), and had lower phosphorus (p = 0.017) and potassium levels (p = 0.038) and higher calcium levels at baseline (p = 0.048). Development of hypophosphatemia was associated with an increased duration of ICU stay (p = 0.014) but not with the other patient outcomes evaluated. Twenty-seven of the 45 patients (60%) who developed hypophosphatemia received phosphorus supplementation with near equal use of intravenous, oral, and combination routes. Only 17 patients (38%) achieved resolution of hypophosphatemia while on CRRT. CONCLUSION: Hypophosphatemia is common, difficult to correct, and contributes to longer ICU stays in patients requiring CRRT. A preemptive approach to address hypophosphatemia including aggressive supplementation strategies to correct phosphorus is warranted in patients requiring CRRT.

[Diagnosis and treatment of hypophosphatemia]. / Que faire de l'hypophosphatémie†?

Phosphate is widely spread in the human body, filling many roles across various tissues, both in the intra- and extracellular space. Serum phosphorus makes up only a slight fraction of the total body stocks but acts as an exchange between the different compartments. Hypophosphatemia is commonly found among hospitalized patients, especially those in an intensive care unit. Clinical manifestations associated with hypophosphatemia are mainly respiratory, neuromuscular, cardiac and hematologic, all of which are more common in the presence of severe hypophosphatemia. Interventional evidence on the benefit of correcting hypophosphatemia is lacking. Currently available recommendations vary and are based on weak evidence.

Le phosphate a un rôle physiologique essentiel dans l'organisme humain, il est ubiquitaire, tant en intracellulaire qu'en extracellulaire. La phosphatémie ne représente qu'une faible proportion du contenu corporel total de phosphate, mais joue un rôle important dans les échanges entre les différents compartiments de l'organisme. L'hypophosphatémie est fréquente chez les patients hospitalisés, en particulier aux soins intensifs. Des manifestations respiratoires, cardiologiques, neuromusculaires et hématologiques peuvent y être associées, pouvant même être à l'origine d'une surmortalité si elle est sévère. A ce jour, il n'existe pas d'évidence du bénéfice de corriger l'hypophosphatémie. Les recommandations pour la correction d'une hypophosphatémie varient et sont basées sur des évidences faibles.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

OBJECTIVE: To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. METHODS: A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. RESULTS: Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. CONCLUSIONS: In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Reliability of calcium-phosphorus (Ca/P) ratio as a new, accurate and inexpensive tool in the diagnosis of some Ca-P disorders.

PURPOSE: The serum calcium/phosphorus (Ca/P) ratio is an accurate tool to differentiate patients with primary hyperparathyroidism (PHPT) from healthy subjects. However, other disorders of the Ca-P metabolism might impair the Ca/P ratio, such as hypophosphatemia (HypoP) not PHPT related. The aim of this study is to examine the diagnostic value of Ca/P ratio in the diagnosis of PHPT and HypoP not PHPT related. METHODS: Single-center, retrospective, case-control study, including 150 patients with PHPT and 306 patients with HypoP, compared with 150 controls. HypoP patients were enrolled among HIV-infected patients by selecting those with Fanconi-like syndrome due to antiretroviral treatment. Parameters which were measured were serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine). RESULTS: The Ca/P ratio was significantly higher in PHPT and HypoP patients, compared to controls (p < 0.0001). At receiver operator characteristic (ROC) curve analysis, the cut-off of 3.56 (2.75 SI) for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 95%; specificity 93%). Among patients with Ca/P ratio above 3.56, the thresholds of 10.3 mg/dL (2.6 mmol/L) for serum Ca (sensitivity 93%; specificity 98%) and 80.5 pg/mL for PTH (sensitivity 91%; specificity 91%) were defined for the specific diagnosis of PHPT. CONCLUSIONS: The Ca/P ratio above 3.56 (2.75 SI) is a highly accurate tool to identify PHPT and HypoP not PHPT-related patients. Thanks to its simplicity, this index can be proposed as a screening and first-line examination in the diagnostic work-up when a disorder of Ca-P metabolism is suspected or should be ruled out.

Efficacy and safety of a phosphate replacement strategy for severe hypophosphatemia in the ICU.

BACKGROUND: Experience with individualized phosphate replacement is limited in patients with severe hypophosphatemia. This study compares the efficacy and safety of an individualized regimen of serum phosphate < 0.4 mmol/l treatment in ICU patients to patients with moderate hypophosphatemia (0.4-0.6 mmol/l). METHODS: This retrospective cohort study included 36 patients with severe and 35 patients with moderate hypophosphatemia. Supplementation dose was calculated according to the equation: phosphate dose (in mmol) = 0.5 x body weight x (1.25 - [serum phosphate]). Sodium-potassium-phosphate was infused at a rate of 10 mmol/hour. Blood samples were taken at baseline and the next morning at 06.00 hrs. RESULTS: Serum phosphate rose to a level > 0.40 mmol/l in all patients with severe hypophosphatemia. Serum phosphate increased to > 0.60 mmol/l in 56% of patients with severe hypophosphatemia and in 86% of patients with moderate hypophosphatemia (p = 0.01). Mild hyperphosphatemia was observed in one patient only (1.53 mmol/l), hyperkalemia was observed in three patients (all three had severe hypophosphatemia, average potassium after supplementation was 5.2 ±; 0.2 mmol/l) and serum calcium levels remained unchanged in both groups. CONCLUSION: Individualized phosphate replacement was effective and safe for both moderate and severe hypophosphatemia, but was more accurate in moderate hypophosphatemia.

[Hypophosphatemia in preterm infants: a bimodal disorder]. / Hipofosfemia en recién nacidos prematuros: un trastorno bimodal.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal / Hypophosphatemia in preterm infants: a bimodal disorder

Las estrategias nutricionales para prematuros extremos con alto aporte de proteínas, han mostrado alteraciones metabólicas con hipofosfemia precoz, especialmente en el grupo de pacientes con restricción de crecimiento intrauterino (Rein). También se presenta hipofosfemia tardía, característica de la enfermedad metabólica ósea. En este artículo se revisan y actualizan conceptos en relación a la fisiopatología del metabolismo del fósforo en recién nacidos prematuros y uso de parenterales precoces en el contexto de enfermedad metabólica ósea. Los artículos fueron identificados en base de datos electrónicas como Pubmed y Rima. Fueron incluidos artículos en inglés y español. Fueron filtrados por título y resumen. La literatura actual propone diversas estrategias de nutrición precoz que permitan asegurar una adecuada cantidad de nutrientes para continuar con el crecimiento y desarrollo extrauterino. En pacientes con nutrición parenteral pero con diferentes aportes de fósforo, o relación calcio: fósforo inadecuada, a mayor contenido de aminoácidos, se presenta hipofosfemia, hipercalcemia, hipomagnesemia, hipokalemia e hiperglicemia, especialmente en casos de Rein. Estas alteraciones se asocian a prolongación de ventilación mecánica, mayor riesgo de displasia broncopulmonar y aumento de sepsis tardía. La hipofosfemia tardía, descrita ya hace muchos años, se presenta con normocalcemia y aumento de fosfatasas alcalinas, en la enfermedad metabólica ósea del prematuro, con alteración de la mineralización en distintos grados, secundaria a un inadecuado aporte de este mineral para los altos requerimientos de estos pacientes. Esta presentación de hipofosfemia precoz y tardía en el prematuro alerta sobre el control oportuno de fosfemia para ajustar el aporte nutricional. En el prematuro con nutrición parenteral precoz, el control en conjunto con la calcemia en la primera semana de vida, especialmente en Rein, permite tratar la hipofosfemia y prevenir sus complicaciones. En hipofosfemia tardía, el seguimiento semanal o quincenal desde las 4 semanas a los prematuros con riesgo, permite lograr un aporte óptimo de minerales.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose adefovir dipivoxil.

OBJECTIVE: To investigate the predictors of hypophosphatemic osteomalacia induced by adefovir dipivoxil (ADV) and to monitor for early detection. PATIENTS AND METHODS: Hospitalized patients who were diagnosed with ADV-related hypo-phosphatemic osteomalacia were recruited and retrospectively analyzed in our hospital from January 2012 to December 2016. A telephone interview was conducted at 1, 3, 6, 9, 12, and 24 months after cessation of ADV. RESULTS: In the 8 patients enrolled in the study, the hypophosphatemic osteomalacia symptoms developed at an average of 5.14 (4-7) years since ADV treatment (10 mg/d). The average alkaline phosphatase (ALP) level was 279.50 (137-548) U/L, which was significantly higher than the normal level (45-125 U/L). The serum phosphorus level was an average of 0.59 (0.43-0.69) mmol/L, which was lower than the normal range (2.06-2.60 mmol/L). Serum calcium levels of the enrolled patients remained within normal limits. Reduced estimated glomerular filtration rate (eGFR <29 mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly progressive systemic bone and joint pain, frequent fractures, trouble in walking, height reduction (4-6 cm), and so on. After cessation of ADV, symptoms like bone pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months after the withdrawal of ADV. However, in 4 patients, renal function failed to return to normal in 24 months. CONCLUSION: More attention should be paid to the duration of ADV treatment. The level of serum phosphorus and ALP, as well as renal function, should be monitored for early detection of potential adverse drug reactions.