Phosphate Absorption Research Articles

9379 From Diagnosis To Treatment: A Comprehensive Approach To Pregnancy-Related Osteoporosis With Teriparatide

Abstract Disclosure: C. Hubers: None. M. Renzu: None. V. Mehta: None. A. Manzoor Qazi: None. A.M. Satei: None. D.K. Yerasuri: None. Introduction: Pregnancy and lactation related osteoporosis (PLO) is a rare but serious condition with significant consequences for maternal and fetal health. Teriparatide's efficacy in treating this condition is promising, particularly given concerns about bisphosphonate use in this population. Clinical Case: A 26-year-old white female sought evaluation for concerns arising after her first pregnancy. Following delivery via Cesarean section, she experienced acute back pain, instability while walking and frequent falls. A subsequent bone scan showed superior end plate fractures of T9, T11, T12, and L1, while an MRI of the lumbosacral spine showed mild acute to subacute compression deformities involving the superior endplates of the L2-L5 vertebral bodies. Despite having Factor V Leiden disease, her medical history is unremarkable for significant chronic conditions or comorbidities affecting bone health. Bone density scans revealed a Z-score of -2.4 in the lumbar spine and -1.6 in the total hip, with a femoral neck Z-score of -1.3. Her lumbar spine T-score was reported as -2.8, reflecting significant bone mineral density (BMD) loss with a BMI of 20.67. She underwent thorough testing to rule out other potential contributory conditions, such as celiac disease and hemochromatosis, but was eventually diagnosed with PLO. Treatment was initiated with teriparatide, administered as a daily 20 µg subcutaneous injection. The patient demonstrated an excellent response, with marked improvements in pain and enhanced ability to perform daily activities. After treatment with teriparatide, the patient’s c-telopeptide also improved. Discussion: PLO is a very rare manifestation of osteoporosis, mainly affecting women with lower BMI and advanced age. The etiology involves hormonal changes, increased calcium demands during pregnancy and lactation, and decreased BMD. Our patient's history and clinical course highlight a compelling instance of PLO, likely attributed to decreased estrogen exposure secondary to amenorrhea and breastfeeding, resulting in increased bone turnover. While bisphosphonates are often recommended for PLO, concerns about safety in pregnant and lactating women underscore the need for alternative treatments like teriparatide. Potential effects on gestational age, neonatal birth weight, and neonatal calcium levels have been observed in newborns with maternal exposure to bisphosphonates. Teriparatide is a synthetic form of parathyroid hormone that works primarily by stimulating osteoblast activity, leading to increased bone formation and BMD. It also enhances calcium and phosphate absorption in the kidneys and intestines, further contributing to its bone-building effects. Our patient's response to teriparatide emphasizes its potential as a safer option in managing PLO, warranting further research to establish comprehensive management guidelines. Presentation: 6/3/2024

7984 A Challenging Case Of Hyperphosphatemic Familial Tumoral Calcinosis

Abstract Disclosure: T.G. de Souza: None. T.J. Weber: None. Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (hFTC) is a rare, autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and the accumulation of calcium phosphate deposits in soft tissues. There are fewer that 150 genetically confirmed cases in the literature. There are no consensus guidelines; therapeutic approaches are guided by case reports or series. This case serves to heighten awareness of therapeutic strategies including global health considerations for the disabled adult with a rare bone disorder. Case: A 32-year-old African-American woman presented to establish care for hFTC, for which she takes ibuprofen for disabling bilateral hip pain. hFTC was diagnosed in early childhood and managed at a large children’s hospital. Therapeutic modalities relied on operative resection of skin lesions on eruption. She describes cosanguinous parentage, consignment to foster care as a child and homelessness as an adult. She has not had adult endocrine care for her hFTC. Her medical comorbidities include major depressive disorder, PTSD and suicide attempt. She reports one uncle with hFTC noting that his phenotype was not significantly disabling and apparent recession of his lesions with age. Her parents did not have symptoms of hFTC. Radiographically, she had amorphous calcium deposits over both hips (her primary sites of severe pain), upper back (site of painless spontaneous eruptions), and left elbow without pain or skin penetration, as well as hyperostosis of the ilium bilaterally. She noticed waxing and waning of her eruptions with her menstrual cycle, such that lesions worsen in the luteal phase. Megestrol acetate also induced new eruptions. Examination shows brown staining to all teeth with several missing teeth. She had a marked lower extremity limb length discrepancy with severe restriction of hip abduction. Blood chemistries were grossly normal, including renal function, calcium, uric acid and PTH. Serum phosphorous was elevated at 5.2 (2.3 - 4.5 mg/dL). CT showed bilateral nephrocalcinosis. We instituted treatment with a low phosphorous diet, sevelamer to reduce intestinal phosphate absorption and acetazolamide to increase urinary phosphate excretion. For her pain and functional disability, we recommended continued NSAIDs, physical therapy and social work consultation to facilitate continued access to care. Conclusions: This case uniquely describes hFTC symptom fluctuation with the menstrual cycle, worsening with increased progesterone, suggesting a possible role of gonadal hormones on FGF-23 biology. It also highlights the socioeconomic burdens that can accompany rare bone disease, which become more pronounced as the patient achieves adulthood. Successful transition of care from pediatric to adult endocrinologist, in addition to engaging multi-disciplinary support, is essential in optimizing life-long care in hFTC. Presentation: 6/1/2024

Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport

Parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) control serum phosphate levels by downregulating the renal Na-phosphate transporter NPT2A, thereby decreasing phosphate absorption and augmenting urinary excretion. This mechanism requires NHERF1, a PDZ scaffold protein, and is governed by the regulator of G protein signaling-14 (RGS14), which harbors a carboxy-terminal PDZ ligand that binds NHERF1. RGS14 is part of a triad of structurally related RGS proteins that includes RGS12 and RGS10. Like RGS14, RGS12 contains a class 1 PDZ ligand. However, unlike RGS14, the larger RGS12 contains an upstream PDZ-binding domain. The studies outlined here examined and characterized the binding of RGS12 with NHERF1 and NPT2A and its function on hormone-regulated phosphate transport. Immunoblotting experiments revealed RGS12 C-terminal PDZ ligand binding to NHERF1. Further structural analysis disclosed that NPT2A engaged full-length RGS12 and the upstream fragment containing the PDZ domain. Neither the downstream RGS12 portion nor RGS14 interacted with NPT2A. PTH and FGF23 profoundly inhibited phosphate uptake in opossum kidney proximal tubule cells. Transfection with human RGS14, or human RGS12, abolished hormone-sensitive phosphate transport as reported for human proximal tubule cells. RGS12 inhibitory activity resides in the downstream region and is comparable to RGS14. The carboxy-terminal RGS12(667–1447) splice variant is prominently expressed in the kidney and may contribute to regulating hormone-sensitive phosphate transport.

The effectiveness of combination of arbuscular mycorrhizal fungi and compost ameliorant on sengon growth in former coal mine soil

Abstract Mining activities give a negative impact to the soil which become the ex-coal mine soil. The soil has a solid soil structure and low nutrient content so is not suitable for planting. The problems need to be improved by being treated with biological agents from soil microorganisms such as Arbuscular Mycorrhizal Fungi (AMF). The provision of AMF on ex-coal mine soil with the addition of ameliorant compost can be one strategy that can be used. AMF can help increase plant growth and help the process of absorption of phosphate (P) by plants. Compost from goat manure can help the association between AMF and plant roots, also being a source of nutrients that are free from chemicals. The plants which suitable for this association are sengon. Sengon commonly used to help revegetation of ex-mining soil because it is able to withstand various conditions of overgrown soil. This study aims to determine the effect of the addition of a combination of AMF and compost on the growth of sengon plants in the soil of ex-coal mines. Observations were made weekly until the age of three months, the best results were the results at the end of the observation. The results showed that the AMF dose and the addition of compost had an effect on percent AMF colonization, increasing plant height, dry weight of plant roots increasing plant stem diameter, and number of leaves.

Tuning surface Mn defects on LaMnO3 perovskite oxides by selective dissolution strategy for enhanced phosphate removal

Selective dissolution is widely used to adjust the surface state of LaMnO3 perovskite oxides. In this study, LaMnO3(LMO) with B-Site vacancies was synthesized using ascorbic acid to selectively remove Mn cations and enhance phosphate adsorption. The optimized LMO with Mn defects (LMO-AA3) presented large surface area, plenty of mesoporosity and suitable electronic structure. Particularly, the adsorption capacity (113.48 mg/g) of LMO-AA3 was about10 times that of LMO. Adsorption experiments showed adsorption occurred both chemically and physically on the heterogeneous adsorption surfaces, as the pseudo-second-order kinetic model and the Redlich-Peterson isotherm model predicted. The stimulated mechanism of LMO-AA3 achieved phosphate absorption through enhancing electrostatic attraction and ligand exchange by –OH groups. Regeneration testing showed that LMO-AA3 can be used for both high and low-concentration purification of phosphate. The selectively remove Mn cations method may offer an appropriate choice for enhancing the material characteristics of effective phosphate capture.

Solid Metal Chemical and Thermal Injury Management.

Solid metals may create a variety of injuries. White phosphorous (WP) is a metal that causes both caustic and thermal injuries. Because of its broad use in munitions and smoke screens during conflicts and wars, all military clinicians should be competent at WP injury identification and acute therapy, as well as long-term consequence recognition. English-language manuscripts addressing WP injuries were curated from PubMed and Medline from inception to January 31, 2024. Data regarding WP injury identification, management, and sequelae were abstracted to construct a Scale for the Assessment of Narrative Review Articles guideline-consistent narrative review. White phosphorous appears to be ubiquitous in military conflicts. White phosphorous creates a characteristic wound appearance accompanied by smoke, a garlic aroma, and spontaneous combustion on contact with air. Decontamination and burning prevention or cessation are key and may rely on aqueous irrigation and submersion or immersion in substances that prevent air contact. Topical cooling is a key aspect of preventing spontaneous ignition as well. Disposal of all contaminated clothing and gear is essential to prevent additional injury, especially to rescuers. Long-term sequelae relate to phosphorous absorption and may lead to death. Chronic or repeated exposure may induce jaw osteonecrosis. Tactical Combat Casualty Care recommendations do not currently address WP injury management. Education and management regarding WP acute injury and late sequelae is essential for acute battlefield and definitive facility care. Resource-replete and resource-limited settings may use related approaches for acute management and ignition prevention. Current burn wound management recommendations should incorporate specific WP management principles and actions for military clinicians at every level of skill and environment.

Absence of claudin-3 does not alter intestinal absorption of phosphate in mice

Intestinal absorption of phosphate is bimodal, consisting of a transcellular pathway and a poorly characterized paracellular mode, even though the latter one contributes to the bulk of absorption under normal dietary conditions. Claudin-3 (Cldn3), a tight junction protein present along the whole intestine in mice, has been proposed to tighten the paracellular pathway for phosphate. The aim of this work was to characterize the phosphate-related phenotype of Cldn3-deficient mice. Cldn3-deficient mice and wildtype littermates were fed standard diet or challenged for 3 days with high dietary phosphate. Feces, urine, blood, intestinal segments and kidneys were collected. Measurements included fecal, urinary, and plasma concentrations of phosphate and calcium, plasma levels of phosphate-regulating hormones, evaluation of trans- and paracellular phosphate transport across jejunum and ileum, and analysis of intestinal phosphate and calcium permeabilities. Fecal and urinary excretion of phosphate as well as its plasma concentration was similar in both genotypes, under standard and high-phosphate diet. However, Cldn3-deficient mice challenged with high dietary phosphate had a reduced urinary calcium excretion and increased plasma levels of calcitriol. Intact FGF23 concentration was also similar in both groups, regardless of the dietary conditions. We found no differences either in intestinal phosphate transport (trans- or paracellular) and phosphate and calcium permeabilities between genotypes. The intestinal expression of claudin-7 remained unaltered in Cldn3-deficient mice. Our data do not provide evidence for a decisive role of Cldn3 for intestinal phosphate absorption and phosphate homeostasis. In addition, our data suggest a novel role of Cldn3 in regulating calcitriol levels.

The Relevance of Phytate for the Treatment of Chronic Kidney Disease.

Diets high in plant-based foods are commonly recommended for people with chronic kidney disease (CKD). One putative advantage of these diets is reduced intestinal phosphate absorption. This effect has been ascribed to phytic acid (myoinositol hexaphosphoric acid) and its anion, phytate, that are present in many plant foods, particularly in the seeds, nuts, grains and fruits of plants. This paper reviews the structure and many actions of phytate with particular reference to its potential effects on people with CKD. Phytate binds avidly to and can reduce gastrointestinal absorption of the phosphate anion and many macrominerals and trace elements including iron, zinc, calcium and magnesium. This has led some opinion leaders to label phytate as an "anti-nutrient." The human intestine lacks phytase; hence, phytate is essentially not degraded in the small intestine. A small amount of phytate is absorbed from the small intestine, although phytate bound to phosphate is poorly absorbed. Clinical trials in maintenance hemodialysis patients indicate that intravenously administered phytate may decrease hydroxyapatite formation, vascular calcification and calciphylaxis. Orally administered phytate or in vitro studies indicate that phytate may also reduce osteoporosis, urinary calcium calculi formation and dental plaque formation. Phytate appears to have anti-inflammatory and antioxidant effects, at least partly due to its ability to chelate iron. Other potential therapeutic roles for phytate, not definitively established, include suppression of cancer formation, reduction in cognitive decline that occurs with aging, and amelioration of certain neurodegenerative diseases and several gastrointestinal and metabolic disorders. These latter potential benefits of phytate are supported by cell or animal research or observational studies in humans. Many of the above disorders are particularly common in CKD patients. Definitive clinical trials to identify potential therapeutic benefits of phytate in CKD patients are clearly warranted.

Aluminium-based metal-organic frameworks for the colorimetric ethephon detection in fruit by paper microsensor

Ethephon (ETH) is a plant growth regulator extensively utilized in agriculture, but its overuse is associated with several health issues. However, detecting ETH sensitively and easily in the field is challenging due to the complexity and time-consuming operation of current approaches. In this study, we synthesized aluminum-based metal-organic frameworks (CAU-1) as fluorescent probes for the detection of ETH in fruit. ETH exposure enhanced and shifted the light green fluorescence of CAU-1 to blue through high absorption of phosphate by electrostatic attraction. We observed a linear correlation between fluorescent intensity and ETH concentration ranging from 2 mg/L to 400 mg/L, with the lowest detection limit at 1 mg/L. This fluorescent analysis exhibited good selectivity towards ETH. To facilitate easy identification of samples in the field, we designed a fluorescent paper-based platform with a logic gate operation, allowing visual distinction of samples containing ETH. We applied this platform to monitor ETH in various fruits, including apples, pears, and tomatoes, through fluorescent spectrum, and visual detection. The platform offered simplicity, speed, ease of use and sensitivity, providing a promising future for ETH detection in agriculture.

Safety and efficacy of burosumab in improving phosphate metabolism, bone health, and quality of life in adolescents with X-linked hypophosphatemic rickets

Background and objectiveX-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (PHEX) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia.Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions.Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few.In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy. MethodsFive Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8–1.2 mg/kg, s. c. QW2). Burosumab was continued for 12–48 months and, once discontinued, patients were followed-up for 6–12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH)2D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3–6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities. ResultsAt entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH)2D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH)2D levels, and in TmP/GFR values (P < 0.05 - P < 0.0001). Serum ALP levels significantly declined (P < 0.05) to normal values. No changes of serum calcium and PTH levels (PNS) were found during burosumab. PROs significantly improved (P < 0.02 - P < 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH)2D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened with a significant reduction in quality of life. These consequences were not observed in the patient who continued burosumab treatment. DiscussionOur data showed that conventional treatment improved only in part the signs and symptoms of XLH. Burosumab was well tolerated and was effective in improving phosphate metabolism, bone health, and PROs. All the benefits of burosumab were lost after its discontinuation. These results suggested that continuing burosumab is required to achieve and maintain the clinical benefits of the treatment during the transition to young adulthood in patients with XLH.

Sodium-dependent phosphate transporter NaPi2b as a candidate for targeted therapy: features of structure, function, and expression

The sodium-dependent phosphate transporter NaPi2b is an integral membrane protein of the SLC34 phosphate transporter family and is an attractive target for precision therapy of several human diseases. Together with other members of this family, the NaPi2b transporter is involved in maintaining phosphate homeostasis in the mammalian body. The NaPi2b transporter gene (SLC34A2) has a broad expression pattern in healthy tissues, including small intestinal epithelial cells, where NaPi2b plays a major role in the absorption of dietary phosphate. NaPi2b transports one divalentorthophosphoric acid residue into cells along with three sodium ions. NaPi2b transport is regulated by dietary phosphate, pH, hormones, and vitamins including vitamin D, estrogen, glucocorticoids, and epidermal growth factor. The NaPi2b transporter exists in two isoforms – 689 and 690 amino acid residues. The molecular weight of NaPi2b depends on the degree of glycosylation and varies from 70 to 100 kDa. According to various sources, the transporter has from 6 to 12 transmembrane domains, 2 co-transport domains, a large extracellular localization domain, as well as N- and C-terminal domains that face the inside of the cell. Impaired NaPi2b function leads to the development of several diseases, including pulmonary alveolar microlithiasis and hyperphosphatemia, and pulmonary alveolar microlithiasis is known to be associated with mutations in the SLC34A2 gene encoding NaPi2b. High levels of NaPi2b have been found in several malignant tumors, including ovary, lung, breast, thyroid, colon, bladder, liver, stomach, kidney, and in gliomas. The tumor-specific conformation of the large extracellular domain of the NaPi2b transporter, mutations, and features of expression of the transporter gene in normal and pathological conditions show that NaPi2b is a promising target for the development of highly selective targeted drugs against it for the treatment of cancer and metabolic disorders.

Selective phosphate removal with manganese oxide composite anion exchange membranes in membrane capacitive deionization

The discharge of excessive phosphorous into water bodies can lead to serious eutrophication threatening aquatic ecosystem. Membrane capacitive deionization (MCDI) is an effective platform for deionizing aqueous streams; however, conventional MCDI is unable to selectively remove targeted ions from a liquid mixture. In this work, we fabricated manganese oxide composite anion exchange membranes (AEMs) for MCDI to enhance phosphate removal selectivity from sodium chloride-sodium dihydrogen phosphate (10:1 M ratio) aqueous mixtures. We systematically investigated several critical factors, such as constant current or voltage operation, applied voltage amount, process stream pH, and manganese oxide (Mn2O3) content in the AEM, on phosphate removal efficiency and phosphate selectivity. A trade-off was observed between phosphate removal and selectivity when increasing the cell voltage. Under the best conditions, a MCDI unit with a 20 wt% Mn2O3 composite AEM and a bipolar membrane facilitated high phosphate removal efficiency of ≥ 31.8 % and a phosphate over chloride selectivity of 1.1 while showing stability for at least 30 cycles. To help understand how Mn2O3 composite AEM boosts phosphate selectivity, static electronic structure calculations were performed, and they revelated that hydrogen phosphate absorption on Mn2O3 composite AEM was 314 kcal/mol more exothermic than that on pristine AEM while chloride adsorption on Mn2O3 composite AEM was 2.2 kcal/mol less exothermic than that on a pristine AEM. Overall, this work presents an effective strategy for selectively removing phosphate from model wastewater solutions and the mechanistic understanding that governs ion selectivity in composite ion-exchange membranes used in MCDI.

#3008 Very low protein diet with ketoanalogues supplementation could start haemodialysis with AVF without additional CVCs insertion

Abstract Background and Aims Nutritional interventions and a low-protein diet (LPD) are a critical point in the management of chronic kidney disease (CKD). Several protein-restricted dietary regimens have been proposed in patients with end stage kidney disease: a typical LPD provides around 0.6–0.7 g·kg meanwhile a very low-protein diet (VLPD) provides around 0.3–0.4 g·kg and it is basically a vegetarian diet which has to be supplemented with essential amino acids (EAA) to satisfy the body nitrogen need and with nitrogen-free ketoanalogues (KA) to recirculate the endogenous urea, whose serum levels are elevated in patients with CKD. KA and EAA reduce the rate of progression of chronic kidney disease and improve the inflammatory state; they reduce the absorption of phosphates and can maintain a good state of nutrition even if associated with diets with very low protein content. On the contrary, an excessively restrictive and inadequate diet in terms of EAA or calorie intake induces a negative nitrogen balance, therefore cachexia. The recommended vascular access to start dialysis treatment is represented by the arteriovenous fistula (AVF). An early referral to the vascular surgeon for vascular access creation is pivotal for deciding on a patient-specific strategy for planning access. Guidelines advise referral at least 3–6 months before the expected start of HD, because time is needed for AVF maturation and possible repeat interventions when it is impaired. An early referral results in more autologous AVFs, which have a better long-term patency, whereas late referral, results in a greater risk of AVF non-maturation and failure and therefore the need for additional central venous catheters (CVCs) to initiate dialysis. Recent studies have shown that pre-dialysis patients who undergo a VLDP + KA require less emergency dialysis access and have better elasticity of the arterial wall, better maturation rates and duration of the AVF and sometimes a reduction in the uremic toxins responsible of endothelial dysfunction. The aim of the study was to evaluate if patients could start haemodialysis with fistula cannulation, without central venous catheter insertion. Method 10 patients, late referral end stage renal disease were enrolled in a prospective, single arm study starting very low protein diet supplemented with ketoanalogues after arteriovenous fistula creation; they were followed with periodically assessment of renal function, uremic toxin, and acid-base balance until they need to start haemodialysis. It was evaluated AVF maturation and needs to additional CVC insertion. Results Patients (3 females, 7 males) mean age was 71.2 years; before AVF creation, baseline mean value was: sCr: 6.46 mg/dl, sUrea: 150 mg/dl, phosphorus: 4.45 mg/dl, bicarbonates: 19.8 mmol/l, eGFR: 8,37 ml/min. After 3 months of VLPD supplemented with KA, eGFR and sCr was stable to 8.25 ml/min and 6.69 respectively, sUrea and phosphorus reduced to 115 mg/dl and 3.8 mg/dl, and bicarbonate increased to 22.4 mmol/l. All 10 patients achieved AVF maturation within 3 months, no one needed CVC insertion. Conclusion In this small group we see how late referral ESRD patients, undergone AVF surgery, after 3 months of VLPD supplemented with KA, had stability of renal function, with reduction of urea and phosphorus, improvement of acid-base balance and achievement of AVF maturation, without needing of CVC insertion. For these reasons VLPD + KA could be useful in delaying haemodialysis start in late referral ESRD patients who have created AVF, without emergency placement of a central venous catheter.

The Intricacies of Renal Phosphate Reabsorption-An Overview.

To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in phosphate and composition of the renal filtrate and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long-held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully, this will raise questions and stimulate new ideas for further research.

Fractura humeral bilateral por deficiencia de vitamina D: reporte de un caso

Introduction: Vitamin D is a fat-soluble vitamin used by the body for bone development and maintenance through the increased absorption of calcium, magnesium, and phosphate. Vitamin D deficiency, or insufficiency, has been identified as a global problem that affects at least one billion people worldwide. The presence of muscle weakness, falls, and fractures associated with vitamin D deficiency is frequent in the elderly; however, its impact on young people is little known. Clinical Case: We present the case of a 34-year-old male with no sun exposure and a history of consuming alcoholic beverages, presenting with progressive muscle weakness and a non-traumatic bilateral humeral fracture associated with vitamin D deficiency. We also describe the diagnostic-therapeutic approach as well as review the literature and its current importance. Conclusions: Vitamin D deficiency is common and often unrecognized, yet it can play an important role in exacerbating underlying pathologies, especially in vulnerable populations. Proximal humerus fractures are common among elderly patients, but not in young people, and less in the absence of trauma. In low-energy fractures without obvious traumatic mechanisms, greater prevalence has been observed in patients with low vitamin levels.

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.

Efficient Recovery of Phosphate from Water Media by Iron-Magnesium Functionalized Lignite: Adsorption Evaluation, Mechanism Revelation and Potential Application Exploration.

Selective phosphorus removal from aquatic media has become an ideal strategy to mitigate eutrophication and meet increasingly stringent discharge requirements. To achieve phosphorus control and resource utilization of low-calorific-value lignite, iron and magnesium salts were used to functionalize lignite, and iron-magnesium functionalized lignite (called IM@BC) was prepared for phosphate recovery from water media. The adsorption properties of IM@BC were systematically evaluated, especially the influence of ambient pH and co-existing ions. The kinetic, isothermal, and thermodynamic adsorption behaviors of IM@BC were analyzed. The adsorption mechanism was revealed by microscopic characterization. The potential application of phosphate-containing IM@BC (P-IM@BC) was explored. The results show that IM@BC has a strong phosphate adsorption capacity, and the maximum adsorption capacity is 226.22 mgP/g at pH = 3. Co-existing CO32- inhibits phosphate adsorption, while coexisting Ca2+ and Mg2+ enhance the effect. At the initial adsorption stage, the amount of phosphate adsorbed by IM@BC continues to increase, and the adsorption equilibrium state is gradually reached after 24 h. The adsorption process conforms to the pseudo-second-order kinetic model (PSO) and Langmuir isothermal adsorption model, and the adsorption process is mainly chemical adsorption. The phosphate absorption capacity is positively correlated with temperature (283.15 K~313.15 K), and the adsorption process is spontaneous, endothermic, and entropy-increasing. Its adsorption mechanism includes electrostatic attraction, ion exchange, surface precipitation, and coordination exchange. IM@BC can efficiently recover phosphate from actual phosphorus-containing wastewater with a recovery efficiency of up to 90%. P-IM@BC slowly releases phosphate from pH 3 to 11. Plant growth experiments showed that P-IM@BC could be used as a slow-release fertilizer to promote the root growth of cowpeas. The novelty of this work lies in the development of a highly efficient phosphate recovery adsorbent, which provides a feasible method of phosphorus control in water media and resource utilization of lignite.

Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.

Many of the pathological consequences of chronic kidney disease can be attributed to an elevation in serum phosphate levels. Current therapies focused on decreasing intestinal phosphate absorption to treat hyperphosphatemia are inadequate. The most effective therapeutic strategy may be to target multiple absorptive pathways. In this study, the ability of a novel inhibitor of the intestinal sodium hydrogen exchanger 3 (NHE3), LY3304000, which inhibits paracellular, diffusional uptake of phosphate, to work in combination with an inhibitor of the active transporter, sodium dependent phosphate cotransporter 2b (NPT2b), LY3358966, was explored. LY3304000 modestly inhibited the acute uptake of phosphate into plasma of rats, while surprisingly, it doubled the rate of phosphate uptake in mice, an animal model dominated by NPT2b mediated acute phosphate uptake. In rats, LY3004000 and LY3358966 work in concert to inhibit acute phosphate uptake. On top of LY3358966, LY3304000 further decreased the acute uptake of phosphate into plasma. Studies measuring the recovery of radiolabeled phosphate in the intestine demonstrated LY3304000 and LY3358966 synergistically inhibited the absorption of phosphate in rats. We hypothesize the synergism is because the NHE3 inhibitor, LY3304000, has two opposing effects on intestinal phosphate absorption in rats, first it decreases diffusion mediated paracellular phosphate absorption, while second, it simultaneously increases phosphate absorption through the NPT2b pathway. NHE3 inhibition decreases proton export from enterocytes and raises the cell surface pH. In vitro, NPT2b mediated phosphate transport is increased at higher pHs. The increased NPT2b mediated transport induced by NHE3 inhibition is masked in rats which have relatively low levels of NPT2b mediated phosphate transport, by the more robust inhibition of diffusion mediated phosphate absorption. Thus, the inhibition of NPT2b mediated phosphate transport in rats in the presence of NHE3 inhibition has an effect that exceeds its effect in the absence of NHE3 inhibition, leading to the observed synergism on phosphate absorption between NPT2b and NHE3 inhibition.

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.

Tenapanor-A Novel Approach for Management of Hyperphosphatemia in End Stage Renal Disease: A Clinical Study Aggregate Review

The critical importance of phosphate regulation in chronic kidney disease (CKD) has been well understood for decades. But new findings, frequently applicable to routine medical care, continue to evolve. Poor health outcomes, greater morbidity, lowered quality of life, and a higher death rate from cardiovascular disease are all linked to the development of CKD-bone mineral ailment. Increased blood phosphate levels are linked to an increased risk of mortality in hemodialysis patients due to changes in phosphate breakdown and declining renal function as CKD advances.In this setting, according to CKD-mineral bone disease recommendations, it is critical to regulate serum phosphate levels in patients with CKD-mineral bone problem. If dialysis and dietary intervention fail to control blood phosphate levels, the use of phosphate binders is advised. Although phosphate binders are successful in lowering blood phosphate levels by actively binding to dietary phosphate, certain individuals have adverse effects that may restrict their use.These medications also have a significant pill load, which might result in poor treatment compliance. Tenapanor, a novel medication, works by inhibiting the sodium/hydrogen exporter isoform 3 (NHE3), which lowers intestinal phosphate absorption primarily by decreasing passive paracellular phosphate flow. Tenapanor also reduces the expression of the sodium phosphorus 2b transport protein (NaPi2b), which limits active transcellular phosphate absorption compensation. This is considered to be more effective phosphorous absorption regulator and a better target for tailored medication therapy. This clinical study aggregate report explores the currently published studies that have evaluated Tenapanor for the treatment of hyperphosphatemia in end stage renal disease patients on haemodialysis.&#x0D; Keywords: Tenapanor, phosphate binding agents, hyperphosphatemia, chronic kidney disease, phosphate control, phosphate binders, phosphate absorption, phosphate absorbtion inhibitor.