Normal Phosphate Levels Research Articles

Clinical Outcomes in Patients with Phosphate Abnormalities After Cardiac Surgery: A Retrospective Cohort Study.

The clinical significance and incidence of phosphate abnormalities in cardiac surgery have not been investigated extensively. We hypothesize that phosphate abnormalities are associated with a longer time to tracheal extubation. This was a single-center, retrospective cohort study in patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. Serum phosphate levels were measured within 6 hours of arrival to the intensive care unit (ICU). Select clinical outcomes were extracted from an intramural database: time to tracheal extubation, hospital length of stay, and in-hospital mortality. The lactate level within 6 hours of arrival to the ICU was extracted as well. A total of 2659 patients were included. There were 502 (18.9%) patients who were found to be hypophosphatemic (phosphate <2.5 mg/dL), 1905 (71.6%) had normal phosphate levels (phosphate 2.5-4.5 mg/dL), and 252 (9.5%) were hyperphosphatemic (phosphate >4.5 mg/dL). Hyperphosphatemia was associated with 26% longer time to tracheal extubation (incident rate ratio, 1.26, 95% confidence interval [CI], 10%, 44%, P = .001), 37% longer hospital length of stay (acceleration factor = 0.63, 95% CI, -43% to -30%); P < .001), and increased in-hospital mortality (odds ratio, 4.0; 95% CI, 2.3-7.1; P < .001) when compared to patients with normal phosphate levels. These associations were not found for hypophosphatemia. Hyperphosphatemia in the immediate postoperative period after cardiac surgery is associated with adverse clinical outcomes. Future studies will need to investigate if actively correcting the phosphate level has an impact on clinical outcomes.

Correlation of serum fibroblast growth factor-23 levels and calcium phosphate products levels in chronic kidney disease; sub analysis of chronic kidney disease-mineral and bone disorder study

&lt;em data-sider-select-id="0e59b1fc-fce5-41b4-b987-316daa778de4"&gt;Introduction: The body produces fibroblast growth factor-23 (FGF-23) to maintain normal phosphate levels when hyperphosphatemia occurs. Production of FGF-23 indirectly causes hypocalcemia. Phosphate and calcium disturbances also occur in chronic kidney disease (CKD), therefore this adaptation mechanism applies. This situation; however, only manifests in the early stages of CKD; if the estimated glomerular filtration rate (eGFR) is less than 30% of normal. This adaptation is no longer adequate and levels of calcium-phosphate (Ca×P) products and FGF-23 still rise. &lt;em data-sider-select-id="f0dc3bf1-1598-419e-9de6-fe837eadc8e6"&gt;Objectives: In this study, the correlation between both the serum levels of FGF-23 and Ca×P products in CKD was analyzed. &lt;em data-sider-select-id="a367eeb1-7c32-4bf0-98ef-e6ae52522dc7"&gt;Patients and Methods: A cross-sectional study including 78 subjects with CKD stages 3 to 5 dialysis was conducted. Serum FGF-23 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method and Ca×P product levels were calculated using the formula calcium (mg/ dL) × phosphate (mg/dL). The Kolmogorov-Smirnov test and Spearman’s test were conducted in the statistical study. If the P value is less than 0.05, the statistical findings are significant. &lt;em data-sider-select-id="e286c166-6c09-432e-b832-c902b1a13b81"&gt;Results: Serum FGF-23 levels and Ca×P product levels were shown to be significantly correlated. This analysis of the two correlations was independent of age and diabetes mellitus (DM). Based on stages of CKD, serum FGF-23 levels and Ca×P product levels were discovered to be significantly correlated only at stage 5 of non-dialysis. &lt;em data-sider-select-id="9b3534d4-deaa-4ccf-8b82-745bb5380661"&gt;Conclusion: Increasing serum FGF-23 levels were correlated with increased Ca×P product levels, particularly in CKD stage 5 non-dialysis subjects. This correlation was independent of age and DM.

Exploring the association between serum phosphate levels and mortality in patients hospitalized with infectious diseases: a nationwide study.

The purpose of this study was to examine associations of serum phosphate levels with mortality, target organ damage and length of hospital stay in adults with infectious diseases hospitalized outside of the intensive care unit. This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. The main exposure variable was the first serum phosphate levels at admission (up to 1 week). The analysis included multivariable logistic regression models and quantile regression. Of 126,088 patients (49% males, mean age: 69.3 years), 24,809 (19.7%) had decreased phosphate levels, 92,730 (73.5%) normal phosphate levels, and 8,549 (6.8%) elevated phosphate levels on admission. Overall- and in-hospital mortality rates were highest among those with hyperphosphatemia (74.5 and 16.4%, respectively), followed by those with normophosphatemia (57.0 and 6.6%), and lastly the hypophosphatemia group (48.7 and 5.6%); p < 0.001 for all. After adjusting for confounders, the lowest predicted mortality rate was observed in the normophosphatemia group. In the multivariable model, hyperphosphatemia conferred a higher probability of target organ damage (OR [95% CI]: 2.43 [2.06-2.86]), while moderate hypophosphatemia conferred a lower probability (OR [95% CI]: 0.73 [0.65-0.82]), compared to normal phosphate levels and extreme hypophosphatemia showed a non-significant association (OR [95% CI]: 0.87 [0.57-1.28]). The associations were independent of renal failure. In a multivariable model, hyperphosphatemia was associated with a slight increase of 0.33 days in length of stay compared to normal phosphate levels. A J-shaped relation was found between phosphate levels and prognosis in patients hospitalized with infectious diseases, regardless of their renal function.

The association between phosphate level at admission and early mortality in acute pancreatitis.

Abnormal phosphate levels are associated with adverse outcomes in critical illness. However, there is scarce evidence on phosphate's impact on acute pancreatitis outcomes, and the few studies examining this subject are relatively small and show conflicting data. We sought to determine the association between phosphate level at admission and the clinical course and outcomes of acute pancreatitis. In this retrospective single-center observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Phosphate levels at admission were classified as normal (2.8-4.5mg/dl), low (below 2.8mg/dl), or high (above 4.5mg/dl). Out of 2308 cases, 1868 patients had documented phosphate levels at admission and were thus included in our final analysis. 1096 (59%) had normal phosphate levels, 686 (37%) had hypophosphatemia, and 86 (4.6%) had hyperphosphatemia on admission. 30-day mortality rates were 3.4%, 3.8%, and 19% in normal, low, and high phosphate levels, respectively. In univariate analysis, hyperphosphatemia was significantly associated with 30-day mortality, with an OR of 6.54 (95% CI 3.39-12.2, p < 0.001; AUC = 0.58). In a multivariate analysis adjusting for age, MAP, GFR, BUN, and pH, hyperphosphatemia remained a statistically significant independent predictor of early mortality (OR-2.93, 95% CI 1.28-6.51, p = 0.009). Hypophosphatemia was not significantly associated with 30-day mortality in univariate analysis, OR of 1.13 (95% CI 0.67-1.87, p = 0.6). Hyperphosphatemia at admission was independently associated with increased 30-day mortality in patients with acute pancreatitis. Hypophosphatemia at admission was not significantly associated with 30-day mortality.

Chronic dialysis patient with severe secondary hyperparathyroidism undergoing parathyroidectomy in Indonesia: a case series

Link of Video Abstract: https://youtu.be/d196XKGsPekBackground: Parathyroidectomy is a method of treating secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD), which has been largely abandoned in developed countries due to the existence of calcimimetic drugs which are reported to be effective in treating secondary hyperparathyroidism in this population. However, in developing countries like Indonesia, the availability of Calcimimetic drugs is still rare and expensive, so that parathyroidectomy can be an option. The study aimed to present four case reports of chronic HD patients with SHPT accompanied by clinical symptoms. As far as our knowledge goes, this is the first case series reported from Indonesia. Case Presentation: This research is a multicenter case series study. All patients had undergone dialysis for five years and complained of body aches. All calcium levels were within the normal range, while three patients had hyperphosphatemia and one patient had normal phosphate levels. All patients had iPTH levels &gt;1000 pg/ml in the last six months. Before the surgery, all patients had received long-term phosphate-binding drugs, including calcium-based and non-calcium-based drugs and vitamin D3 agonists. All patients underwent total parathyroidectomy with autotransplantation of parathyroid tissue in the right antebrachial regions, except for the second patient who received the transplant in the left antebrachial region due to an AV fistula in the right arm. Conclusion: In dialysis patients, especially in developing countries, approximately 10.7% of them experience SHPT with PTH levels &gt;1,000 pg/mL, and one study in Indonesia showed that around 35% of patients undergoing chronic hemodialysis had PTH levels &gt;200 pg/ml, making parathyroidectomy a highly possible option considering that medications such as cinacalcet are more expensive and not widely available.

Frequency and Risk Factors of Hypophosphatemia in Patients Admitted to Emergency Intensive Care Unit in Zagazig University Hospitals.

Inorganic phosphate is a major electrolyte that participates in many functional and integral processes in the human body. Low Pi levels may lead to multiple organ dysfunction. It is estimated to occur in 40-80% of intensive care unit (ICU) patients. However, it may be ignored during the initial evaluation in ICU. This prospective cross-sectional study included 500 adult ICU cases in two groups; a group with normal Pi levels and a group with hypophosphatemia. All admitted patients were subjected to full history taking, and clinical, laboratory, and radiological evaluation. Collected data were coded, processed, and analyzed using statistical package for social sciences (SPSS) software. Among 500 adult ICU patients; 56.8% had normal phosphate levels while the remaining 43.2% had low phosphate levels. Patients in the hypophosphatemia group were associated with a significantly higher Acute Physiological and Chronic Health Evaluation (APACHE II) score, a longer hospital and ICU stay, a higher incidence of mechanical ventilation use with a longer duration on it, and a significantly higher mortality rate. Risk factors for hypophosphatemia include a higher APACHE II score, longer stay in the hospital and ICU, a higher ratio of mechanical ventilation, and a higher mortality rate. El-Sayed Bsar AEM, El-Wakiel SAR, El-Harrisi MAH, Elshafei ASH. Frequency and Risk Factors of Hypophosphatemia in Patients Admitted to Emergency Intensive Care Unit in Zagazig University Hospitals. Indian J Crit Care Med 2023;27(4):277-282.

Molecular Mechanisms of PTH/PTHrP Class B GPCR Signaling and Pharmacological Implications.

The classical paradigm of G protein-coupled receptor (GPCR) signaling via G proteins is grounded in a view that downstream responses are relatively transient and confined to the cell surface, but this notion has been revised in recent years following the identification of several receptors that engage in sustained signaling responses from subcellular compartments following internalization of the ligand-receptor complex. This phenomenon was initially discovered for the parathyroid hormone (PTH) type 1 receptor (PTH1R), a vital GPCR for maintaining normal calcium and phosphate levels in the body with the paradoxical ability to build or break down bone in response to PTH binding. The diverse biological processes regulated by this receptor are thought to depend on its capacity to mediate diverse modes of cyclic adenosine monophosphate (cAMP) signaling. These include transient signaling at the plasma membrane and sustained signaling from internalized PTH1R within early endosomes mediated by PTH. Here we discuss recent structural, cell signaling, and in vivo studies that unveil potential pharmacological outputs of the spatial versus temporal dimension of PTH1R signaling via cAMP. Notably, the combination of molecular dynamics simulations and elastic network model-based methods revealed how precise modulation of PTH signaling responses is achieved through structure-encoded allosteric coupling within the receptor and between the peptide hormone binding site and the G protein coupling interface. The implications of recent findings are now being explored for addressing key questions on how location bias in receptor signaling contributes to pharmacological functions, and how to drug a difficult target such as the PTH1R toward discovering nonpeptidic small molecule candidates for the treatment of metabolic bone and mineral diseases.

Phosphate Frustration: Treatment Options to Complement Current Therapies.

Hyperphosphatemia eventually develops in almost all patients with advanced chronic kidney disease and is associated with negative clinical outcomes. Thus, guidelines recommend targeting treatment to normal phosphate levels in patients with chronic kidney disease. Despite low phosphorus diets, clearance by dialysis, and phosphate binder use, many patients with chronic kidney disease on dialysis are unable to consistently achieve and maintain serum phosphate concentrations <5.5 mg/dL. A chart audit of patients on dialysis receiving phosphate binders showed that 74 to 86% were unable to consistently achieve serum phosphate ≤5.5 mg/dL over 6 months. Furthermore, although there is evidence that serum phosphate concentrations <4.5 mg/dL are associated with improved survival and cardiovascular outcomes, real-world phosphate control data suggest achieving and maintaining this goal for most patients would be extremely challenging, if not near impossible, using current therapies. As phosphate binders can only remove approximately 300 mg of the 2,500 mg or more daily dietary phosphate intake, therapeutic innovations are necessary to improve phosphate management. We present treatment options to complement current therapies including tenapanor, a novel sodium/hydrogen exchanger isoform 3 inhibitor that blocks the dominant paracellular phosphate absorption pathway and has been shown to reduce phosphate levels in several clinical trials.

MO811: A Closed Loop Audit of CKD-MBD Parameters in Patients Receiving Home Haemodialysis in North West London Centre

Abstract BACKGROUND AND AIMS Hyperphosphatemia is common in end-stage renal disease and increases the risk of fractures, cardiovascular disease and all-cause mortality. Achieving normal phosphate levels is dependent on optimization of dialysis, diet and phosphate medication. Home haemodialysis (HHD) offers exciting opportunities for individualised approaches to management, allowing for a more liberal, lifestyle-centred patient experience. Our aim was to determine, in line with the UK Renal Association 2015 standards for Chronic Kidney Disease—Mineral Bone Disease (CKD-MBD), the percentage of patients in the North West London HHD program with: METHOD We conducted a retrospective review of the six most recent monthly biochemistry results for serum phosphate, corrected calcium and PTH levels of all patients actively receiving HHD under the care of Hammersmith Hospital (n = 33) between January and September 2020. Subsequently, a monthly multidisciplinary review of blood tests (with nephrologists, specialist nurses and dieticians) focusing on CKD-MBD parameters was implemented to facilitate timely prescription changes. Additionally, two questionnaires were conducted: (1) an adapted Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) questionnaire assessed adherence with phosphate binders and (2) a diet questionnaire assessed dietary phosphate knowledge. At the end of 12 months, a re-audit was conducted in the patients from the original cohort (n = 23; following 4 transplants, 3 in-centre transitions and 3 deaths). RESULTS The initial audit revealed that of the 33 included patients, 14 (42%) recorded all bone parameters within the target range. Examining CKD-MBD parameters individually, 27 (82%) had adjusted calcium within target range [4 (12%) &amp;lt; 2.2 mmol/L and 1 (3%) &amp;gt; 2.6 mmol/L], 22 (66%) had a serum PTH in target range [9 (27%) &amp;gt; 9× ULN and 2 (8%) &amp;lt; 2× ULN, excluding those with parathyroidectomies] and 17 (51%) recorded a median serum phosphate within target [11 (33%) &amp;gt; 1.7 mmol/L and 5 (15%) &amp;lt;1.1 mmol/L]. Table 1 summarizes baseline demographics of the final audit group (n = 23). Re-audit after 12 months revealed 10 (43%) recorded all bone parameters within the target range. Examining CKD-MBD parameters individually, PTH targets had improved (from 66% to 83%). This was associated with increased use of calcimimetics, with 3 (17%) recording PTH &amp;gt; 9× ULN [from 9 (27%) at baseline]. However, there was no significant change in phosphate [12 (54%) within the target range, 7 (29%) above the range] and calcium [18 (78%) within the target range]. Of the 23 patients included for final analysis, 15 (65%) were actively prescribed phosphate binders. The BAASIS questionnaire revealed notable non-adherence, with 8 (53%) admitting to having missed doses in the last month, 5 (33%) consistently missing &amp;gt;4 doses and 6 (40%) not consuming alongside meals. Additionally, the dietary questionnaire revealed a lack of knowledge of hidden sources of dietary phosphate in all surveyed patients (n = 11 responses). CONCLUSION Based on UK Renal Association 2015 standards for CKD-MBD, in patients undergoing HHD:

Abstract #1183932: Management Challenge in Hyperphosphatemic Tumoral Calcinosis

Tumoral calcinosis (TC) is a rare metabolic disorder causing abnormal calcium salt deposition in different peri-articular soft tissue regions. The most common site is lateral hips. TC can be primary normo-phosphatemic or primary hyperphosphatemic. It can be secondary also, seen commonly in chronic renal failure. We describe a case report of 14 years old girl who presented with primary hyperphosphatemic tumoral calcinosis with recurrent swellings even after surgery and medical therapy. A 14-year-old girl presented to us with recurrent soft tissue mass and persistent hyperphosphtemia associated with pain and decreased movements. She was operated twice for this soft tissue. Her medical record stated that patient had undergone 6 surgeries till date for these periarticular swellings at multiple sites (right elbow, left hip, right hip and left knee) but it recurs after 3-4 months of surgery and progressively enlarges in size. Physical examination revealed firm tender 9 X 4 cm oval shaped swelling in the left greater trochanteric area with restriction in abduction, internal rotation and rotator movements at hip joint and 4 X 4 cm circular hard, non-sessile mass over medial aspect of left knee joint with slight difficulty in complete flexion of knee. Biochemical work up showed hyperphosphatemia with normal serum calcium and low iPTH levels, low serum 25 hydroxyvitamin-D and slightly high 1,25 vitamin D with calculated TmP/GfR of 5.7 mg/dl. C-terminal FGF23 level was grossly elevated to 1200 RU/ml. Histological evaluation of previously surgically excised soft tissue mass revealed fibrocollagenous stroma with clusters of crystalline and amorphous calcium enclosed by band of histiocytes and lymphocytes compatible with findings seen in tumoral calcinosis. Presently the patient is maintaining the near normal phosphate level with oral phosphate restricted diet and multiple phosphate binder and acetazolamide. Hyperphosphatemic Tumoral calcinosis is a disorder of dysregulated phosphate metabolism characterized by hyperphosphatemia and deposition of calcium salts in soft tissue regions of the body usually in the periarticular sites. FGF23 is a 251-amino acid peptide secreted by osteoblasts, osteocytes and erythroid precursor cells of the bone marrow that plays a critical role in phosphate regulation. In the proximal tubule of the kidney, FGF23 binds to the FGF receptor 1 (FGFR1) and its co-receptor KLOTHO, downregulating expression of the sodium-phosphate cotransporters NPT2a and NPT2c, which leads to phosphaturia. Additionally, FGF23 inhibits 1-alpha-hydroxylase and stimulates 25-vitamin D-24 hydroxylase, resulting in decreased 1,25-(OH)2-vitamin D (1,25D), the active form of vitamin D. Recently an entitity named autoimmune hyperphosphataemic tumoral calcinosis has been reported in which pathogenetic autoantibodies mediate FGF23 resistance.Treatment is to lower serum phosphorus by blocking dietary phosphate absorption and increasing renal phosphate excretion. Surgery is usually reserved for patients with significant pain or restricted movements of joint.

Tumor-Induced Osteomalacia With Normal Fibroblast Growth Factor-23 (FGF23) and Idiopathic Hypercalciuria

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome characterized by low serum phosphate, phosphaturia, inappropriately low/normal levels of serum calcitriol, and normal or elevated levels of fibroblast growth factor-23 (FGF23). Finding this mesenchymal tumor is challenging since it is usually benign, small, slow-growing, and is localized in the appendicular skeleton. We report a 58-year-old male patient who arrived at the endocrinology outpatient clinic due to slowly progressive low back pain and generalized weakness since the age of 48. On physical examination, only a reduced range of motion was noted. Laboratory tests revealed hypophosphatemia with normal parathyroid hormone (PTH) levels, normal serum calcium, high 24-hour urine calcium, normal 1,25-dihydroxyvitaminD levels, low renal threshold phosphate concentration (TmPO4/GFR), and high FGF23. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) reported a hypermetabolic extramedullary lesion in the C1-C2 vertebral bodies measuring 1.5 x 1.1 cm. Two months after the 18F-FDG PET/CT, complete excision of the cervical tumor was performed. The pathology ward reported a histiocytic mesenchymal neoplasm with accumulations of multinucleated giant cells compatible with phosphaturic mesenchymal tumor. After surgery, the patient’s hypophosphatemia was completely resolved. With this, the diagnosis of TIO was confirmed. The patient remains asymptomatic, with normal phosphate levels at one year of follow-up. Hypophosphatemia due to renal losses in an adult patient is a challenging diagnosis and one must consider TIO, autosomal dominant hypophosphatemic rickets, fibrous dysplasia, and even Fanconi syndrome. FGF23 can be extremely useful during the diagnostic approach since acquired dependent hypophosphatemia (FGF23 ≥ 30 RU/mL) highly suggests TIO. In this case report, we want to highlight the paramount importance of adequate tumor screening in adult patients with acquired FGF23-dependent hypophosphatemia. TIO is a reversible cause of hypophosphatemia with potentially disabling consequences if left untreated. These manifestations are non-specific (bone pain and muscle weakness), while others are progressive and severely disabling (bone deformities and multiple fractures). In this case report, we want to highlight the paramount importance of adequate tumor screening in adult patients with acquired hypophosphatemia, and the crucial lead that phosphate and vitamin D regulating hormones (FGF23) have for suspecting TIO.

Hypophosphatemia after hemodialysis and its association with some clinical complications in patients with chronic kidney disease.

Background: Beyond the adverse effects of hyperphosphatemia in patients with chronic kidney disease (CKD(, hypophosphatemia has also been proposed as a common challenge after dialysis. Therefore, the present study aimed to evaluate the serum phosphate level immediately after hemodialysis (HD) and its association with some clinical complications in CKD patients.Methods:The present cross-sectional study was conducted on 54 eligible CKD patients undergoing regular hemodialysis. Blood samples were taken, prior to the start and immediately after the end of hemodialysis to determine the serum levels of urea, creatinine, sodium, potassium, phosphorus, PTH, blood sugar and albumin. Moreover, the clinical complications of patients including muscle cramps, nausea, vomiting, headache, confusion, weakness and inability to speak are assessed by a questionnaire, before and after HD.Results:As we expected, the mean of serum creatinine, urea and phosphate levels significantly decreased after dialysis. Post-dialysis hypophosphatemia was graded as mild (3.5 > P ≥ 2.5 mg/dl), moderate (2.5 > P ≥ 1 mg/dl), and severe (<1 mg/dl) based on serum phosphate levels. The frequency of mild and moderate hypophosphatemia was 39.2% and 45.1 %, respectively. None of the participants had severe hypophosphatemia and 13.7% had normal phosphate levels. There was a significant correlation between post-dialysis hypophosphatemia and incidence of nausea and confusion after adjusting for confounding factors.Conclusion:To our knowledge, this is the first time that the possible association of some of the post-dialysis clinical complications with hypophosphatemia was investigated. Future large-scale studies are required to confirm the association of post-dialysis hypophosphatemia with clinical complications.

Tubular phosphate handling: references from child to adulthood in the era of standardized serum creatinine.

The assessment of phosphate homeostasis in clinical practice relies not only on circulating phosphate levels but also on phosphate tubular reabsorption, ideally assessed using the tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR). TmP/GFR reference values were established before the onset of isotope-dilution mass spectrometry-standardized (IDMS) creatinine assays and thus need to be updated. Our objective is to provide reference values for TmP/GFR from childhood to adulthood, using the gold-standard of GFR assessment and IDMS-standardized creatinine values. We retrospectively analysed all the inulin and iohexol clearances [measured glomerular filtration rate (mGFR)] performed in children and in adults screened for a living-donation in our unit since the beginning of IDMS-creatinine assays. TmP/GFR was calculated on a fasting sample, using the conventional formula without correction for tubular reabsorption of phosphate (TRP) in subjects below 19 years of age. A total of 2051 subjects (1711 children, 340 adults), aged from 1.9 to 73.4 years with normal GFR, normal phosphate and normal calcium levels, were included for TmP/GFR analysis. As expected, there was a progressive decrease along puberty in both genders of plasma phosphate and TmP/GFR, the decrease occurring earlier in girls. After the age of 19 years, there was a stabilization of plasma phosphate and TmP/GFR levels until the age of 55 years, phosphate levels and TmP/GFR being slightly lower in men than in women. We present the largest cohort describing TmP/GFR reference values in the era of IDMS-standardized creatinine assays. We believe that these data will help physicians to better diagnose and manage patients with abnormal phosphate metabolism in daily clinical routine.

Hydration effect on kidney function and serum electrolyte in children with tumor lysis syndrome (TLS) and risk of TLS.

Tumor lysis syndrome (TLS) is a life-threatening oncology emergency disorder, which may cause acute kidney injury (AKI), arrhythmias, seizures, and sudden death. Hydration is used to prevent TLS in medium-high risk patients, and treatment in TLS patients. According to the pediatric protocol in Dr. Soetomo District General and Teaching Hospital, close monitoring is required to prevent the progression of hematological malignancy towards TLS. The study aimed to analyze the hydration effect on potassium, calcium, and phosphate levels; serum creatinine (sCr); and blood urea nitrogen (BUN) level. This was an observational and prospective study conducted at Dr. Soetomo District General and Teaching Hospital for four months on 15 pediatric hemato-oncology patients who got TLS and in risk of TLS. Laboratory parameters were observed in 11days, pre and post hydration. Among the 15 patients who met the inclusion criteria, there were eight TLS patients and seven TLS risk patients. After hydration administration 67% of TLS patients achieved normal potassium level, 75% achieved normal phosphate level, 0% achieved normal calcium level, and 50% achieved normal sCr and BUN levels. Meanwhile, TLS risk patients reached normal level in all parameters. This difference in performance is caused by disease progression. Hydration can maintain serum electrolytes and renal function in a normal range, preventing TLS in TLS risk patients. In TLS patients, hydration only tends slow the progression of the disease.

Pulmonary alveolar microlithiasis: Blizzard of lung.

Pulmonary alveolar microlithiasis (PAM) is a rare inherited disorder in which patients present with either nonspecific signs and symptoms or are asymptomatic. Clinical-radiological dissociation is a commonly seen feature of the disease. Majority of cases are diagnosed in second and third decade of life, although presentation in paediatric and elderly population is also reported. Pathognomonic radiological findings, with normal calcium and phosphate levels can confirm the diagnosis without the need of further investigations in large number of cases. A high index of suspicion and knowledge of the disease is of paramount importance as it has a wide range of presentation and variable course thus posing a diagnostic challenge. We present two cases of this rare disease in elderly females with distinct presentations although with similar and characteristic radiological findings along with a brief review of literature of the disease.

A Challenging Case of Phosphaturic Mesenchymal Tumor With Primary Hyperparathyroidism

Background: Localization of tumor-induced osteomalacia (TIO) is often challenging. Primary hyperparathyroidism (HPT) following curative surgery for TIO is rarely reported. Clinical Case: A 49-year-old man presented with fragility rib fractures, generalized bone pain, and muscle weakness worsening over the past 3 years. Rheumatologic workup was negative. Initial tests showed elevated levels of parathyroid hormone (PTH) 114.1 pg/mL (14–72 pg/mL) and alkaline phosphatase (ALP) 283 IU/L (44–174 IU/L), reduced levels of 25(OH)D 16 ng/mL (30–100 ng/mL), 1,25(OH)2D 9 pg/mL (18–72 pg/mL), and phosphorus 1.6 mg/dL (2.5–4.9 mg/dL), calcium levels of 9.2 mg/dL (8.5–10.1 mg/dL), and eGFR 58 mL/min/1.73 m2. A sestamibi scan showed normal parathyroid uptake. The diagnosis was secondary HPT due to chronic kidney disease and vitamin D deficiency. The patient was treated with D3 and phosphate. During a 2-year follow-up, the patient reported improvement of pain and weakness with no additional fractures. Further investigations showed persistent hypophosphatemia with elevated urinary fractional phosphate excretion (44%, ref. <20%), indicating renal phosphate wasting. Fibroblast Growth Factor 23 (FGF23) was high, 291 RU/mL (0–180 RU/mL). DXA results were consistent with osteopenia. TIO was suspected. At a 3-year follow-up, investigations included three whole-body 18F-FDG PET-CT scans revealing several areas suspicious for tumor presence. However, multiple MRIs were inconclusive. Laboratory tests showed persistent hypophosphatemia (despite D3 and phosphate treatment), elevated FGF23 (1330 RU/mL) and PTH (274.4 pg/mL), and normal calcium, 25(OH)D, and 1,25(OH)2D. The patient subsequently underwent 68Ga DOTATATE PET-CT, which revealed a somatostatin receptor-positive lesion involving the left upper lobe of the lung. The mass was resected without complications. Histopathology was compatible with a phosphaturic mesenchymal tumor. At a 6-month postoperative follow-up, the patient reported dramatically improved symptoms with decreased weakness and pain, normal phosphate, calcium, ALP, and FGF23 (160 RU/mL) levels, while DXA results were significantly improved. Phosphorus supplementation was discontinued. At follow-up 3 years post-surgery, the patient had slowly rising PTH (126.3 pg/mL) and calcium (10.1–10.6 mg/dL) levels with normal phosphate, 25(OH)D, and FGF23 (174 RU/mL) levels. A diagnosis of primary HPT was made. Further evaluation was deemed unnecessary since the patient did not meet the criteria for surgical treatment. The development of primary HPT was considered mechanistically related to long-standing hypophosphatemia and hypovitaminosis D stimulating PTH production. Conclusion: This case report highlights the pitfalls contributing to delayed diagnosis of TIO and alerts clinicians to the potential development of primary HPT after curative surgery for TIO.

Primary Hyperparathyroidism Presenting With Atrial Fibrillation and Calcified Pericardial Effusion

Abstract Background: Primary hyperparathyroidism is the most common cause of hypercalcemia and is frequently associated with skeletal and renal complications. It affects the older population and female gender more commonly. Cardiovascular complications due to altered calcium homeostasis are not well recognised or studied but recently cases of calcification of the pericardium, myocardium, valves and dysrhythmias have been reported. Case: A 47-year old female presented to her GP with atrial fibrillation. Initial blood tests revealed an incidental hypercalcaemia; an adjusted calcium of 2.77 (normal 2.20-2.60mmol/L), raised PTH level of 14.0 (normal 1.6–6.9pmol/L), normal phosphate level and thyroid profile. 25-OH vitamin D level was low 39 (normal 50-120nmol/L). Autoantibody screens and CRP was normal. She was initiated on edoxaban, bisoprolol, and cholecalciferol and treated with a short course doxycycline for a presumed chest infection. There was no history of previous pericarditis but she had long standing hypertension and was obese with BMI of 37kg/m2. Retrospectively patient had sustained a recent wrist fracture and reported classic symptoms of hypercalcemia including fatigue, polydipsia, nocturia, constipation, depression in the endocrinology clinic. Further blood tests found a high C-terminal telopeptide (CTX) level of 0.68 (0.10-0.50ug/L) indicative of high bone turnover.24 urinary calcium/creatinine clearance ratio was 0.0189mmol/mmol (R&amp;gt;0.01 for exclusion of FHH). She was prepped for DC cardioversion and Echocardiogram demonstrated Moderate sized pericardial effusion with some organisation but good biventricular function and dilated LA. Subsequent localisation studies with SPECT CT neck revealed a 9mm parathyroid adenoma along with calcified persistent moderate pericardial effusion putting the patient at risk of pericardial constriction. Patient was referred to the parathyroid surgeon for consideration of urgent parathyroidectomy and will be followed up by the cardiologist to see the impact of normalisation of hypercalcemia on the cardiac complication. It is thought that already established calcification of pericardial effusion is unlikely to resolve but achieving normocalcemia could slow the progression of pericardial calcification and improve bone turnover makers by switching off the excess parathyroid hormone. Patient will be followed up with repeat Echocardiogram post parathyroidectomy to elucidate the effects. Conclusion:Cardiac complications of primary hyperparathyroidism are increasingly becoming more evident with the advent and use of SPECT-CT for localising parathyroid adenomas. Simple screening tests like electrocardiogram may potentially point towards a cardiovascular complication and should be considered routinely in hypercalcaemic patients. Further studies to understand the mechanism of developing cardiac complication in such patients are needed.

Hyperparathyroidism Tumoral calcinosis: A case report

Tumoral calcinosis (TC) is a rare locally aggressive lesion characterised by extra-articular soft tissue deposition of the calcium phosphate around large joints & small joints. The exact aetiology is not known. A 11–year–old female presented with a painful progressive swelling around the medial aspect of 1st metatarsal right foot over a 6–month duration. Routine laboratory results showed a normal haemogram, and normal calcium and high phosphate levels & para thyroid level. Imaging showed a soft tissue calcified mass around 1st metatarsal medial aspect of right foot. The cut surface of the excised mass showed myxoid material with areas of calcification. On microscopy, there were typical features of Tumoral calcinosis.

Hospital-acquired serum phosphate derangements and their associated in-hospital mortality

BackgroundWe aimed to report the incidence of hospital-acquired hypophosphataemia and hyperphosphataemia along with their associated in-hospital mortality.MethodsWe included 15 869 adult patients hospitalised at a tertiary medical referral centre from...

C-Terminal, but Not Intact, FGF23 and EPO Are Strongly Correlatively Elevated in Patients With Gain-of-Function Mutations in HIF2A: Clinical Evidence for EPO Regulating FGF23

Fibroblast growth factor 23 (FGF23) is a key phosphate- and vitamin D-regulating hormone. FGF23 circulates as an intact 251 amino acid protein or N- and C-terminal degradation products. Hormone activity resides in the intact molecule, but it has been suggested that high levels of the C-terminal protein can interfere with intact FGF23 (iFGF23) activity. New evidence points to involvement of the hypoxia-inducible factor (HIF)/erythropoietin (EPO)/iron pathway as important in FGF23 physiology. Exactly how this pathway regulates FGF23 is not clear. Various in vitro, in vivo, and clinical studies involving perturbations in this pathway at various points have yielded conflicting results. Many of these studies are complicated by the confounding, independent effect of renal insufficiency on FGF23. To gain insight into FGF23 physiology, we studied 8 patients with a rare paraganglioma/somatostatinoma syndrome who had elevated blood EPO levels as a result of somatic gain-of-function mutations in HIF2A (EPAS1) that stimulate tumoral EPO production. All patients had normal renal function. EPO levels varied; most were very elevated and highly correlated with C-terminal FGF23 (cFGF23) levels that were also markedly elevated. Blood phosphate and intact FGF23 levels were normal. These data from patients with normal renal function in whom HIF activation was the inciting event suggest a direct role of the HIF/EPO pathway in FGF23 transcription and translation. They also demonstrate that posttranslational regulation was finely tuned to maintain normal blood phosphate levels. Additionally, normal phosphate and intact FGF23 levels in the setting of markedly increased C-terminal FGF23 levels suggest intact FGF23 action is not attenuated by C-terminal FGF23. Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).