Renal Phosphate Research Articles

Impact of lymphangiogenesis on renal phosphate handling following kidney injury

Overconsumption of inorganic phosphate (Pi) causes tubular cell damage and kidney dysfunction, and hyperphosphatemia can lead to Ca2+ retention, vascular calcification, and cardiovascular disease. Conversely, kidney injury and chronic kidney disease (CKD) cause hyperphosphatemia and Pi retention. We hypothesized that the damage caused by chronic Pi consumption likely induces kidney lymphangiogenesis and that changes to renal lymphatic density may alter kidney mineral handling. We identified significant lymphangiogenesis and increased expression of the lymphatic growth factors VEGF-C/D in kidneys of mice fed a 2% Pi diet for 2 months and as early as three weeks of diet. We then utilized “KidVD” mice, a mouse model of kidney-specific inducible expression of VEGF-D, to expand renal lymphatic density and test Pi handling. Mineral handling was largely normal in male and female KidVD mice compared to littermates on Pi diet. In a Pi-driven CKD model mice were injured with 10 mg/kg cisplatin dose, allowed to recover for 2 weeks, then challenged with chow or 2% Pi diet for 3 weeks with VEGF-D induction. This resulted in Pi retention in all mice. Pi handling in both male and female KidVD mice were normal to controls. Female KidVD, however, demonstrated significantly increased Ca2+ excretion compared to controls. Circulating FGF23 levels were significantly elevated in male and female with VEGF-D overexpression. Gene expression of Fgfr1 was also significantly increased in male and female KidVD mice. Renal lymphangiogenesis thus appears to specifically impact Ca2+ retention through the FGF23-Fgfr1 axis. National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK119497). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nutritional risks and consequences of meat-only diets for dogs and cats

Suitable nutrition is one of the most significant issues that always needs to be considered in the health mainte-nance of living beings. One of the misconcep-tions of many societies is the exclusive feeding of meat to cats and dogs. Dogs and cats are carnivorous animals; more specifically, cats are strict or true carni-vores, while dogs are omnivores. Although cats are true carni-vores, an exclusive diet of meat will not cover their needs. Wholly meat-based diets might be rich in many nutri-ents and minerals, but they are poor in digesti-ble carbohydrates and fiber. Lack of carbohy-drates can cause gas-trointestinal problems and diarrhea. Also, due to hypovitaminosis A and D caused by such diets, skeletal diseases can be one of the seri-ous consequences. High dietary phosphate > 11.8 g in dry matter (DM) reduces renal phosphate reabsorption and increases vulnera-bility to chronic kidney disease. As phosphate excretion and reduction of calcium reabsorption continue, bone decom-position, symptoms of osteoporosis, and sec-ondary hyperparathy-roidism occur. In wholly meat-based canine di-ets, a lack of carbohy-drates compels the an-imal to use protein in the gluconeogenesis process to produce glu-cose. As a result, the body goes through pro-tein deficiency and its side effects. To main-tain digestive system health and prevent diar-rhea, the diet must in-clude soluble fiber. Al-so, the presence of car-bohydrates and fats is essential. Preserving the correct calcium-to-phosphorus ratio (Ca:P) can be solved by adding carbohydrates or using meats with a lower phosphorus content.

The effects of burosumab on growth, nephrocalcinosis and cardiovascular outcomes in children with X-linked hypophosphatemia: a single-center experience

PurposeX-linked hypophosphatemia (XLH) is the most common cause of inherited rickets. It is characterized by chronic hypophosphatemia due to increased levels of Fibroblast Growth Factor 23 hormone (FGF23), renal phosphate wasting, and decreased renal vitamin D hydroxylation. Burosumab, an anti-FGF23 antibody, was approved in 2018 for XLH children.MethodsThis retrospective single-center study assessed the progression of clinical, biological, renal, and cardiovascular outcomes of XLH patients who started burosumab before 18 years of age, between July 2018 and June 2022.ResultsIn total, 12 children began burosumab treatment at a median age of 10.1(2.7–14.7) years, after 7.6 (1.1–11.3) years of conventional therapy. The last follow-up was 2.7(0.8–4.7) years after burosumab initiation, with 10 patients with at least 2 years of follow-up. Regarding the progression of anthropometric parameters, only height SDS significantly increased from baseline at the last follow-up. Regarding the biological parameters, as expected, at 12 months after starting burosumab and at the last follow-up, phosphate and alkaline phosphatase levels significantly improved. Although not significant, there was a trend towards an early increase of osteocalcin and crosslaps during the first months of therapy. Before starting burosumab, 5 patients (42%) had nephrocalcinosis (1 stage 1, 4 stage 2). One patient displayed a complete resolution of nephrocalcinosis after 1 year of treatment, and one patient showed improvement of nephrocalcinosis. No nephrocalcinosis appeared in a patient while being treated with burosumab. Cardiac ultrasounds remained normal in all.ConclusionOur real-life data confirm that burosumab improves outcomes in XLH children, including nephrocalcinosis and growth.

Review of childhood genetic nephrolithiasis and nephrocalcinosis.

Nephrolithiasis (NL) is a common condition worldwide. The incidence of NL and nephrocalcinosis (NC) has been increasing, along with their associated morbidity and economic burden. The etiology of NL and NC is multifactorial and includes both environmental components and genetic components, with multiple studies showing high heritability. Causative gene variants have been detected in up to 32% of children with NL and NC. Children with NL and NC are genotypically heterogenous, but often phenotypically relatively homogenous, and there are subsequently little data on the predictors of genetic childhood NL and NC. Most genetic diseases associated with NL and NC are secondary to hypercalciuria, including those secondary to hypercalcemia, renal phosphate wasting, renal magnesium wasting, distal renal tubular acidosis (RTA), proximal tubulopathies, mixed or variable tubulopathies, Bartter syndrome, hyperaldosteronism and pseudohyperaldosteronism, and hyperparathyroidism and hypoparathyroidism. The remaining minority of genetic diseases associated with NL and NC are secondary to hyperoxaluria, cystinuria, hyperuricosuria, xanthinuria, other metabolic disorders, and multifactorial etiologies. Genome-wide association studies (GWAS) in adults have identified multiple polygenic traits associated with NL and NC, often involving genes that are involved in calcium, phosphorus, magnesium, and vitamin D homeostasis. Compared to adults, there is a relative paucity of studies in children with NL and NC. This review aims to focus on the genetic component of NL and NC in children.

The calcium-sensing receptor has only a parathyroid hormone-dependent role in the acute response of renal phosphate transporters to phosphate intake.

The kidney controls systemic inorganic phosphate (Pi) levels by adapting reabsorption to Pi intake. Renal Pi reabsorption is mostly mediated by sodium-phosphate cotransporters NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) that are tightly controlled by various hormones including parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). PTH and FGF23 rise in response to Pi intake and decrease NaPi-IIa and NaPi-IIc brush border membrane abundance enhancing phosphaturia. Phosphaturia and transporter regulation occurs even in the absence of PTH and FGF23 signaling. The calcium-sensing receptor (CaSR) regulates PTH and FGF23 secretion, and may also directly affect renal Pi handling. Here, we combined pharmacological and genetic approaches to examine the role of the CaSR in the acute phosphaturic response to Pi loading. Animals pretreated with the calcimimetic cinacalcet were hyperphosphatemic, had blunted PTH levels upon Pi administration, a reduced Pi-induced phosphaturia, and no Pi-induced NaPi-IIa downregulation. The calcilytic NPS-2143 exaggerated the PTH response to Pi loading but did not abolish Pi-induced downregulation of NaPi-IIa. In mice with a dominant inactivating mutation in the Casr (CasrBCH002), baseline NaPi-IIa expression was higher, whereas downregulation of transporter expression was blunted in double CasrBCH002/PTH knockout (KO) transgenic animals. Thus, in response to an acute Pi load, acute modulation of the CaSR affects the endocrine and renal response, whereas chronic genetic inactivation, displays only subtle differences in the downregulation of NaPi-IIa and NaPi-IIc renal expression. We did not find evidence that the CaSR impacts on the acute renal response to oral Pi loading beyond its role in regulating PTH secretion.NEW & NOTEWORTHY Consumption of phosphate-rich diets causes an adaptive response of the body leading to the urinary excretion of phosphate. The underlying mechanisms are still poorly understood. Here, we examined the role of the calcium-sensing receptor (CaSR) that senses both calcium and phosphate. We confirmed that the receptor increases the secretion of parathyroid hormone involved in stimulating urinary phosphate excretion. However, we did not find any evidence for a role of the receptor beyond this function.

The molecular sociology of NHERF1 PDZ proteins controlling renal hormone-regulated phosphate transport.

Parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) control extracellular phosphate levels by regulating renal NPT2A-mediated phosphate transport by a process requiring the PDZ scaffold protein NHERF1. NHERF1 possesses two PDZ domains, PDZ1 and PDZ2, with identical core-binding GYGF motifs explicitly recognizing distinct binding partners that play different and specific roles in hormone-regulated phosphate transport. The interaction of PDZ1 and the carboxy-terminal PDZ-binding motif of NPT2A (C-TRL) is required for basal phosphate transport. PDZ2 is a regulatory domain that scaffolds multiple biological targets, including kinases and phosphatases involved in FGF23 and PTH signaling. FGF23 and PTH trigger disassembly of the NHERF1-NPT2A complex through reversible hormone-stimulated phosphorylation with ensuing NPT2A sequestration, down-regulation, and cessation of phosphate absorption. In the absence of NHERF1-NPT2A interaction, inhibition of FGF23 or PTH signaling results in disordered phosphate homeostasis and phosphate wasting. Additional studies are crucial to elucidate how NHERF1 spatiotemporally coordinates cellular partners to regulate extracellular phosphate levels.

Is there a Place for Klotho in Alzheimer’s disease?

Alzheimer’s disease, a major healthcare concern, lacks an effective pharmacological therapy to change its irreversible progression. In this work, we present Klotho, a protein associated with aging that is involved in the regulation of numerous physiological processes and is a serious candidate to be a pharmacological target to act on. Klotho’s mRNA has been found in neurons of a variety of brain regions (cortex, hippocampus). The best studied and prominent function of Klotho is as the co-receptor of fibroblast growth factor 23 (FGF23), through which Klotho controls renal phosphate excretion and vitamin D metabolism. Reduced serum levels of Klotho in mice have been associated with a shorter life expectancy and with numerous pathological conditions such as renal disease, vascular calcification, neurodegeneration, and others. Moreover, overexpression of Klotho leads to opposite effects resulting in increased survival rates. In this review we address different signaling pathways in which Klotho is involved in one way or another, focusing on those pathways that could serve as pharmacological targets to modify the evolution of Alzheimer’s disease. We describe how Klotho inhibits signaling cascades involved in cellular senescence, fibrosis, inflammation, and apoptosis all of which are mediated by tumor growth factor β (TGF- β), nuclear factor kappa K (NF- κ B), insulin-like growth factor 1 (IGF-1) or Wnt. We also highlight how Klotho is able to activate anti-inflammatory and antioxidant signaling pathways. Although there are no drugs that act specifically on Klotho, compounds currently on the market such as hormone-based drugs, pravastatin, losartan, fosinopril, and rapamycin have been shown to increase the expression of this protein and are also discussed.

Serum total testosterone is associated with phosphate and calcium excretion in response to oral phosphate loading in healthy middle-aged males.

Androgen receptors are expressed in the kidney and serum testosterone is negatively associated with serum phosphate in males, suggesting a role of testosterone in renal phosphate handling. In this cross-sectional study, we examined the association of serum total and free testosterone with acute phosphate and calcium excretion in males in response to an oral phosphate challenge. Thirty-five healthy adult males with normal baseline testosterone levels consumed a 500mg phosphorus drink and the urinary excretion of minerals, as well as levels of relevant circulating parameters, were assessed at baseline and hourly for 4 h. Serum total testosterone was positively associated with overall phosphate excretion (r=0.35, p=0.04) and calcium excretion (r=0.44, p=0.00) in response to the challenge. Serum free testosterone was positively associated with post-challenge calcium excretion (r=0.34, p=0.048), but significance was not reached for phosphate excretion (r=0.31, p=0.07). Serum total and free testosterone were not associated with parathyroid hormone, fibroblast growth factor-23, or vitamin D-key factors implicated in phosphate and calcium regulation. Overall, higher serum total testosterone levels in healthy middle-aged males are associated with a greater capacity to acutely excrete phosphate and calcium after a single oral phosphate challenge, suggesting potential ramifications of testosterone deficiency related to mineral homeostasis.

Clinical administration of cinacalcet in parathyroid diseases

Cinacalcet has emerged as an effective therapeutic option for the management of secondary hyperparathyroidism (SHPT) and chronic kidney disease-mineral and bone disorder (CKD-MBD). Through its modulation of the calcium-sensing receptor (CaSR), cinacalcet demonstrates considerable clinical benefits in maintaining parathyroid hormone and serum calcium levels within target ranges. It offers a valuable addition to the available treatment options for patients with these conditions. Cinacalcet binds to the CaSR on parathyroid cells, increasing its sensitivity to extracellular calcium. This results in decreased parathyroid hormone (PTH; parathormone), release through inhibition of intracellular signaling pathways involved in PTH synthesis and secretion. Cinacalcet also indirectly reduces serum calcium and phosphorus levels by suppressing PTH-mediated bone resorption and enhancing renal phosphate excretion.

Family analysis and literature study of hereditary hypophosphatemic rickets with hypercalciuria

BackgroundHereditary hypophosphatemia rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterised by reduced renal phosphate reabsorption leading to hypophosphataemia, rickets and bone pain. Here, we present a case of HHRH in a Chinese boy.Case presentationWe report a 11-year-old female proband, who was admitted to our hospital with bilateral genuvarum deformity and short stature. Computed Tomography (CT) showed kidney stones, blood tests showed hypophosphatemia, For a clear diagnosis, we employed high-throughput sequencing technology to screen for variants. Our gene sequencing approach encompassed whole exome sequencing, detection of exon and intron junction regions, and examination of a 20 bp region of adjacent introns. Flanking sequences are defined as ±50 bp upstream and downstream of the 5′ and 3′ ends of the coding region.The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039), and the pathogenic variant sites were annotated using Annovar. Subsequently, the suspected pathogenic variants were classified according to ACMG’s gene variation classification system. Simultaneously, unreported or clinically ambiguous pathogenic variants were predicted and annotated based on population databases. Any suspected pathogenic variants identified through this analysis were then validated using Sanger sequencing technology. At last, the proband and her affected sister carried pathogenic homozygous variant in the geneSLC34A3(exon 13, c.1402C > T; p.R468W). Their parents were both heterozygous carriers of the variant. Genetic testing revealed that the patient has anLRP5(exon 18, c.3917C > T; p.A1306V) variant of Uncertain significance, which is a rare homozygous variant.ConclusionThis case report aims to raise awareness of the presenting characteristics of HHRH. The paper describes a unique case involving variants in both theSLC34A3andLRP5genes, which are inherited in an autosomal recessive manner. This combination of gene variants has not been previously reported in the literature. It is uncertain whether the presence of these two mutated genes in the same individual will result in more severe clinical symptoms. This report shows that an accurate diagnosis is critical, and with early diagnosis and correct treatment, patients will have a better prognosis.

Phosphaturic mesenchymal tumor: management and outcomes of ten patients treated at a single institution.

Phosphaturic mesenchymal tumor (PMT) is a rare tumor that causes tumor-induced osteomalacia. Patients present with non-specific symptoms secondary to renal phosphate wasting and decreased bone mineralization. We sought to assess: (1) What are the common presenting features, laboratory and imaging findings, histologic findings of phosphaturic mesenchymal tumors? (2) What are the available treatment strategies for phosphaturic mesenchymal tumors and their long-term outcomes in terms of local recurrence and symptom control after treatment? We retrospectively identified patients with a histologic diagnosis of PMT located in the axial or appendicular skeleton, or surrounding soft tissues. A total of 10 patients were finally included in our study. Median tumor size was 1.9cm (range, 1.1 to 6.1) and median time from symptom onset to diagnosis was 3years (range, 0.5 to 15years). All patients but one presented with hypophosphatemia (median 1.9mg/dL, range 1.2 to 3.2). Pre-operative FGF-23 was elevated in all cases (median 423.5 RU/mL, range 235 to 8950). Six patients underwent surgical resection, three were treated percutaneously (radiofrequency ablation or cryoablation), and one refused treatment. Only one patient developed local recurrence and no patients developed metastatic disease. At last follow-up, nine patients showed no evidence of disease and one was alive with disease. Phosphaturic mesenchymal tumor is a rare tumor presenting with non-specific symptoms. Surgery is the standard treatment when negative margins can be achieved without significant morbidity. In patients with small tumors in surgically-inaccessible areas, radiofrequency ablation or cryoablation can be performed successfully.

The Diagnostic Odyssey in Children and Adolescents With X-linked Hypophosphatemia: Population-Based, Case-Control Study.

X-linked hypophosphatemia (XLH) is a rare genetic disorder causing renal phosphate wasting, which predicates musculoskeletal manifestations such as rickets. Diagnosis is often delayed. To explore the recording of clinical features, and the diagnostic odyssey of children and adolescents with XLH in primary care electronic healthcare records (EHRs) in the United Kingdom. Using the Optimum Patient Care Research Database, individuals aged 20 years or younger after January 1, 2000, at date of recorded XLH diagnosis were identified using Systematized Nomenclature of Medicine Clinical Terms (SNOMED)/Read codes and age-matched to 100 controls. Recording of XLH-related clinical features was summarized then compared between cases and controls using chi-squared or Fisher's exact test. In total, 261 XLH cases were identified; 99 met the inclusion criteria. Of these, 84/99 had at least 1 XLH-related clinical feature recorded in their primary care EHR. Clinical codes for rickets, genu varum, and low phosphate were recorded prior to XLH diagnosis in under 20% of cases (median of 1, 1, and 3 years prior, respectively). Rickets, genu varum, low phosphate, nephrocalcinosis, and growth delay were significantly more likely to be recorded in cases. This characterization of the EHR phenotypes of children and adolescents with XLH may inform future case-finding approaches to expedite diagnosis in primary care.

Influence of hydroxyurea on tubular phosphate handling in sickle cell nephropathy

ObjectiveThis study aims to evaluate the markers of tubular phosphate handling in adults with sickle cell anemia (SCA) and the influence of hydroxyurea (HU), the degree of anemia and Hb F concentration on these markers. MethodsEighty-eight steady state SCA patients in outpatient follow-up in Fortaleza, Ceara, Brazil and 31 healthy individuals were included in this study. Vitamin D (25OHD) was measured by enzyme-bound fluorescence assay, intact parathyroid hormone (iPTH) by electrochemiluminescence, and serum and urinary phosphate and creatinine by colorimetric methods. Details of Hb F and HU use were obtained from clinical records. Tubular reabsorption of phosphate (TRP) and maximum tubular reabsorption of phosphate (MTRP) were calculated. SCA patients were stratified according to the use of HU, degree of anemia and percentage of Hb F. The significance level was set for p-values <0.05. ResultsCompared to controls the 25OHD level (25 ± 11 vs. 30 ± 9 pg/mL) was lower in SCA, while serum phosphate and MTRP were higher (3.86 ± 0.94 vs. 3.46 ± 0.72 and 3.6 ± 1.21 vs. 3.21 ± 0.53, respectively). There was no significant difference in iPTH, TRP and phosphaturia. Serum phosphate showed correlation with TRP (r = 0.32; p-value = 0.008) and MTRP (r = 0.9; p-value <0.001) in SCA. Patients taking HU, especially those with Hb F >10 % presented reduced serum phosphate levels, and TRP and MTRP rates. Those with mild anemia presented reduced serum phosphate levels and MTRP rates. ConclusionSerum phosphate levels and renal phosphate reabsorption rate were increased in SCA. HU use, high Hb F concentration and total Hb were associated with better control of tubular phosphate handling markers.

Bilirubin Down-Regulates Oxidative Stress and Fibroblast Growth Factor 23 Expression in UMR106 Osteoblast-Like Cells.

Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate and vitamin D metabolism in the kidney, and its higher levels in plasma are associated with poorer outcomes in kidney and cardiovascular diseases. It is produced by bone cells upon enhanced oxidative stress and inhibits renal phosphate reabsorption and calcitriol (active form of vitamin D) production. Bilirubin, the final product of the heme catabolic pathway in the vascular bed, has versatile biological functions, including antioxidant and anti-inflammatory effects. This study explored whether bilirubin alters FGF23 production. Experiments were performed using UMR106 osteoblast-like cells. Fgf23 transcript levels were determined by quantitative real-time polymerase chain reaction, C-terminal and intact FGF23 protein levels were determined by enzyme-linked immunosorbent assay, and cellular oxidative stress was assessed by CellROX assay. Unconjugated bilirubin down-regulated Fgf23 gene transcription and FGF23 protein abundance; these effects were paralleled by lower cellular oxidative stress levels. Also, conjugated bilirubin reduced Fgf23 mRNA abundance. Bilirubin down-regulates FGF23 production in UMR106 cells, an effect likely to be dependent on the reduction of cellular oxidative stress.

Significance of phosphate in internal medicine

Phosphate is essential for bone metabolism and for energy provision. Phosphate homeostasis is achieved by hormonal feedback mechanisms, predominantly parathyroid hormone, fibroblast growth factor 23 and calcitriol, with renal phosphate absorption taking on a special role. Although even large deviations from the serum normal range are rarely symptomatic, the health consequences can be significant. Essentially, the clinically relevant disturbances in phosphate balance can be attributed to three mechanisms: 1. shifts of phosphate between the extracellular space and the cytosol; 2. inadequate phosphate reabsorption in the kidney; 3. decreased intestinal phosphate absorption. Knowledge of physiology enables diagnosis and therapy of phosphate disorders.

Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients

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

P-17 Hypophosphatemia related to intravenous iron therapy: A case report

Abstract Introduction Intravenous iron supplementation is a good alternative to oral iron replacement in iron deficiency anaemia. Intravenous iron formulations such as ferric carboxymaltose allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important complication of ferric carboxymaltose is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). In this case, we aimed to present our patient with this rare side effect of intravenous iron replacement. Clinical Case A 40-year-old female patient who has no chronic systemic disease was admitted to our endocrinology service for fatigue and weakness. In the patient's history, it was learned that she had been treated with 2500 mg intravenous iron replacement (ferric carboxymaltose) for iron deficiency anaemia in the last month. In the laboratory tests; serum phosphorus 1.05 mg/dl (normal 2.5-4.5 mg/dl), corrected calcium 8.45 mg/dl (normal 8.4-10.2 mg/dl), 25-OH vitamin D 31.4 µg/L (normal &amp;gt;30 µg/L), parathormone 83.2 pg/ml (normal 15-65 ng/ml), alkaline phosphatase 63 U/L (normal 35-105 U/L). Fractional excretion of phosphate (FePO4) confirmed renal phosphate wasting (FePO4: 28.6%; normal &amp;lt;5%). Urinary protein and glucose were negative. FGF23 measured 71 pg/ml (normal &amp;lt;59 pg/mL). Intravenous iron-induced hypophosphataemia was suspected. After initiation of oral phosphate and 1,25-dihydroxyvitamin D3 supplementation, serum phosphate rose to reference range (Figure 1). The patient was taken to outpatient follow-up. Conclusion Physicians should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses.Figure 1.Patient phosphorus data during follow-up

Tumor-induced osteomalacia due to a phosphaturic mesenchymal maxillary tumor

ABSTRACT Tumor-induced osteomalacia is a rare paraneoplastic syndrome with hypophosphatemia due to renal phosphate wasting. The clinical presentation is bony pains and muscle wasting. A 23-year-old male presented to us in a wheelchair with joint pain and muscle weakness for 5 years. There was no history of a similar disease in the family. Treatment with non steroidal anti inflammatory drugs, steroids, and infliximab was unsuccessful. Positive examination findings revealed tenderness and swelling in both ankle and knee joints, tenderness in hip joints, proximal myopathy, and power grade 4/5 in the proximal leg muscles. On evaluation, he was found to have severe hypophosphatemia [serum phosphate 1.2 mg/dl], decreased renal phosphate absorption [tubular maximum for phosphate reabsorption adjusted for glomerular filtration rate (TMP/GFR) of 1.04], increased fibroblast growth factor 23 (FGF23), and decreased 1,25 dihydroxy vitamin D levels. Fluorodeoxyglucose-positron emission tomography (FDG PET-CT) revealed a left maxillary tumor. Histopathology revealed a mesenchymal tumor. Tumor excision resulted in cure of the patient’s symptoms and the normalization of serum phosphate levels and TMP/GFR.

Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

Evaluation of dental manifestations in X-linked hypophosphatemia using orthopantomography.

X-linked hypophosphatemia (XLH) is the most common inherited form of rickets. The presence of sequence variations in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene is associated with increased production of fibroblast growth factor 23 (FGF23). This results in renal phosphate wasting and impaired skeletal mineralization. Spontaneous dental abscesses, caused by endodontic infections resulting from hypomineralization of dentin, are a known dental complication of XLH. There is no objective method to evaluate the severity of dentin dysplasia. The purpose of this study was to develop a quantitative method to evaluate dentin dysplasia using orthopantomography that would allow the values in patients with XLH to be compared with the values in healthy participants of the same age. The severity of dentin dysplasia was analyzed by measuring the pulp cavity area of the tooth using orthopantomographic images. The teeth analyzed were mandibular second primary molars and mandibular first permanent molars with complete root formation. Teeth with dental caries, restorations, or root resorption were excluded. This retrospective observational study included a total of 200 images of healthy participants (aged 2-15 years) divided into five age groups and 42 images of 17 patients with XLH. There was a significant tendency for the pulp cavity area to decrease with increasing age in primary and permanent teeth. The pulp chambers of patients with XLH were larger than those of healthy participants in primary and permanent teeth. We have established a method of using orthopantomography for quantitative assessment of dentin dysplasia in XLH from the primary dentition to the permanent dentition. Evaluating the severity of dentin hypomineralization by this method is useful in the diagnosis of the dental manifestations of XLH. Early diagnosis of XLH enables oral management and leads to prevention of dental abscesses.