Loss Of Phosphate Research Articles

TUMOR INDUCED OSTEOMALACIA: A CASE REPORT

Background:Tumor-induced osteomalacia (TIO), which is also known as oncogenic osteomalacia, is an uncommon paraneoplastic syndrome characterized by a renal phosphate loss causing hypophosphatemia, leading to rickets in children and osteomalacia in adults. It is caused by mesenchymal tumors, which secrete FGF-23 (fibroblast growth factor-23) and rarely other phosphotonins. It can present with a wide range of symptoms and there is often a delay in its diagnosis. Early diagnosis is important and surgical excision can cure the disease in most patients, thus preventing the complications.We report a case of TIO, who was diagnosed at an early stage and underwent curative surgery. Case presentation: A 30 years old female presented with pain in both legs, more severe in the left leg since about 1 year. She also had difficulty in walking, low back ache, muscle pain, mild pain in both the knee joints as well. On examination, she had limping gait, muscle power in the left leg was grade 3-4 otherwise, there was no significant findings on examination. Blood investigations showed elevated alkaline phosphatase (ALP)- 387IU/ml, low serum phosphorus- 1.2mg/dl, normal calcium - 9.8mg/dl, 25-OH Vitamin D- 24.69ng/ml, Parathyroid hormone (PTH)- 61pg/ml.Other blood tests were unremarkable. X- rays of both the legs and pelvis showed a classicalpseudo-fracture in proximal part of both the fibulae and proximal part of the right femur. This suggested hypophosphatemicosteomalacia. TmP/GFR was found to be very low (1.4mg/dl), which confirmed renal phosphate wasting. Later we got Fibroblast growth factor – 23 (FGF-23)- 617RU/ml, which was elevated. This confirmed FGF-23 related hypophosphatemicosteomalacia. In view of the patients age, onset of symptoms, lack of family history, absence of dental and hearing abnormalities, we suspected an acquired rather than a genetic cause. The patient underwent whole body Gallium-68 DOTANOC PET scan, which revealed somatostatin receptor expressing soft tissue density lesion in subcutaneous plane in the mid- anterior right leg, suggestive of FGF-23 secreting mesenchymal tumor.The patient was initially treated with replacement dose of oral phosphorus and calcitriol, along with calcium and vitamin D supplements. Later the patient underwent surgery for excision of the tumor in the right leg. The tumor was around 2cm size and the histopathology was suggestive of gaint cell rich tumor- possibly a phosphaturic mesenchymal tumor. Post surgery, the patient had significant improvement in her symptoms, gait improved and pain reduced. The serum phosphorus level was 3.8mg/dl post-operatively. The serum phosphorus level was maintained without phosphorus replacement. The patient was advised to repeat FGF-23 levels, but the patient failed to get it done. Conclusion: The diagnosis of TIO requires high index of suspicion and should always be looked as a differential diagnosis when we are evaluating a patient with osteomalacia. A detailed history and examination followed by a step wise biochemical evaluation and imaging is important to diagnose TIO in early stages. Surgical resection of the causative tumor will lead to definitve cure of the disease in most patients and avoids the complications like osteoporosis and fractures, thus improving the quality of life of the patients.

Scribble scrambles parathyroid hormone receptor interactions to regulate phosphate and vitamin D homeostasis

G protein-coupled receptors, including PTHR, are pivotal for controlling metabolic processes ranging from serum phosphate and vitamin D levels to glucose uptake, and cytoplasmic interactors may modulate their signaling, trafficking, and function. We now show that direct interaction with Scribble, a cell polarity-regulating adaptor protein, modulates PTHR activity. Scribble is a crucial regulator for establishing and developing tissue architecture, and its dysregulation is involved in various disease conditions, including tumor expansion and viral infections. Scribble co-localizes with PTHR at basal and lateral surfaces in polarized cells. Using X-ray crystallography, we show that colocalization is mediated by engaging a short sequence motif at the PTHR C-terminus using Scribble PDZ1 and PDZ3 domain, with binding affinities of 31.7 and 13.4 μM, respectively. Since PTHR controls metabolic functions by actions on renal proximal tubules, we engineered mice to selectively knockout Scribble in proximal tubules. The loss of Scribble impacted serum phosphate and vitamin D levels and caused significant plasma phosphate elevation and increased aggregate vitamin D3 levels, whereas blood glucose levels remained unchanged. Collectively these results identify Scribble as a vital regulator of PTHR-mediated signaling and function. Our findings reveal an unexpected link between renal metabolism and cell polarity signaling.

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

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

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0mmol/L, HCO3- 22.0mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20mmol/20mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25±7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. NCT03976440 (registered 6 June 2019).

Influence of enzymatic cross-linking on the apparent viscosity and molecular characteristics of casein micelles at neutral and acidic pH

Individual caseins represent almost 80% of the protein in milk, they are organized as protein assemblies called casein micelle (CM). The micelle is a heat-resistant structure, but it becomes dissociated in acidic environments. Microbial transglutaminase (mTGase) promotes the stability of the CM under acidic environments by catalyzing the formation of covalent cross-links. However, no quantitative data are available concerning the structure of the CM at pH 3.0 as a function of the progress of the enzymatically induced cross-linking reaction, measured through a polymerization degree (DP). This study aims to provide information on the cross-linked CM structure at acidic pH (3.0) and neutral pH (7.0) according to their DP and correlate these changes with the viscosity of the dispersions. The size, the molar mass, the apparent density, and the molecular shape of the casein micelle (CM-0%) and cross-linked CM at three cross-linking degrees (TG-41%, TG-51%, TG-56%) were determined using Asymmetrical-Flow-Field-Flow-Fractionation coupled with light scattering techniques. At pH 7.0, the cross-linked CM depicts an increase in the apparent density and a spherical shape due to intra-molecular cross-linking. At pH 3.0, the loss of the colloidal calcium phosphate (CCP) leads to a change in the shape and the density, decreasing the viscosity of the CM dispersions. A master curve describing the evolution of apparent viscosity as a function of DP suggests that DP is the key parameter to tune the viscosity of acidified casein dispersions and predicts structural changes.

Matrix Development for the Detection of Phosphorylated Amyloid-β Peptides by MALDI-TOF-MS.

Amyloid-β (Aβ) peptides, including post-translationally modified variants thereof, are believed to play a key role in the onset and progression of Alzheimer's disease. Suggested modified Aβ species with potential disease relevance include Aβ peptides phosphorylated at serine in position eight (pSer8-Aβ) or 26 (pSer26-Aβ). However, the published studies on those Aβ peptides essentially relied on antibody-based approaches. Thus, complementary analyses by mass spectrometry, as shown for other modified Aβ variants, will be necessary not only to unambiguously verify the existence of phosphorylated Aβ species in brain samples but also to reveal their exact identity as to phosphorylation sites and potential terminal truncations. With the aim of providing a novel tool for addressing this still-unresolved issue, we developed a customized matrix formulation, referred to as TOPAC, that allows for improved detection of synthetic phosphorylated Aβ species by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. When TOPAC was compared with standard matrices, we observed higher signal intensities but minimal methionine oxidation and phosphate loss for intact pSer8-Aβ(1-40) and pSer26-Aβ(1-40). Similarly, TOPAC also improved the mass spectrometric detection and sequencing of the proteolytic cleavage products pSer8-Aβ(1-16) and pSer26-Aβ(17-28). We expect that TOPAC will facilitate future efforts to detect and characterize endogenous phosphorylated Aβ species in biological samples and that it may also find its use in phospho-proteomic approaches apart from applications in the Aβ field.

Mild Hypophosphatemia-Associated Conditions in Children: The Need for a Comprehensive Approach.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

Impact of X-Linked Hypophosphatemia on Muscle Symptoms

X-linked hypophosphatemia (XLH) is the most common hereditary form of rickets and deficiency of renal tubular phosphate transport in humans. XLH is caused by the inactivation of mutations within the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene and follows an X-dominant transmission. It has an estimated frequency of 1 case per 20,000, and over 300 distinct pathogenic variations have been reported that result in an excess of fibroblast growth factor 23 (FGF23) in the serum. Increased levels of FGF23 lead to renal phosphate loss, decreased serum 1,25-dihydroxyvitamin D, and increased metabolism of 1,25-dihydoxyvitamin D, resulting in hypophosphatemia. Major clinical manifestations include rickets, bone deformities, and growth retardation that develop during childhood, and osteomalacia-related fractures or pseudo-fractures, degenerative osteoarthritis, enthesopathy, dental anomalies, and hearing loss during adulthood, which can affect quality of life. In addition, fatigue is also a common symptom in patients with XLH, who experience decreased motion, muscle weakness, and pain, contributing to altered quality of life. The clinical and biomedical characteristics of XLH are extensively defined in bone tissue since skeletal deformations and mineralization defects are the most evident effects of high FGF23 and low serum phosphate levels. However, despite the muscular symptoms that XLH causes, very few reports are available on the effects of FGF23 and phosphate in muscle tissue. Given the close relationship between bones and skeletal muscles, studying the effects of FGF23 and phosphate on muscle could provide additional opportunities to understand the interactions between these two important compartments of the body. By describing the current literature on XLH and skeletal muscle dysfunctions, the purpose of this review is to highlight future areas of research that could contribute to a better understanding of XLH muscular disability and its management.

PSAT219 Renal Phosphate Wasting Caused by ENPP-1 mutation.

Abstract Background Increased renal phosphate loss can be Fibroblast Growth Factor-23 (FGF-23) dependent or independent. FGF-23 reduces expression of Sodium-Phosphate co-transporters, responsible for phosphate reabsorption; and by inhibition of 1-alpha hydroxylation of 25-OH-D3. Reduced serum concentration of 1, 25-OH2-D3 results in secondary hyperparathyroidism. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) mutation is one of the rarest causes of hypophosphatemia, which causes FGF-23 dependent hypophosphatemia. Case description 31-year-old female referred to endocrinology for evaluation of recurrent nephrolithiasis despite normalization of PTH and serum Calcium (Ca) after right inferior parathyroid adenoma resection. Repeated renal stone analysis revealed calcium phosphate as the major stone composition. Patient achieved mid parental height, denied history of calcium or phosphate metabolism disorders/ rickets in the family. Physical exam was not suggestive of rickets and skeletal survey showed normal bone mineralization. Initial labs following parathyroid adenoma resection showed normal Ca 9.7 mg/dl, PTH 47 pg/ml, Phosphorus (Ph) 2.3 mg/dl, 25-OH-D3 51 ng/ml, albumin 3.9 g/dl, Mg 1.8 mg/dl. Repeat fasting labs six months later revealed Ca 9 mg/dl, Ph 1.7 mg/dl, 25-OH-D3 52 ng/ml, PTH 67.5 pg/ml and albumin 3.7 g/dl. Persistent low serum phosphate was evaluated further by a 24-hour urine collection which revealed high urine phosphate of 828 mg/day, Ca 181 mg/day, Mg 23 mg/day and creatinine was 1485 mg/day. Tubular reabsorption of phosphorus was 77% (normal: &amp;gt;80%), indicating renal phosphate wasting. Serum FGF-23 on two different days was &amp;gt;180 RU/ml. Next-generation sequencing tested positive for heterozygous ENPP-1 gene mutation variant c1441C&amp;gt;T (p. Arg481Trp). Patient was started on oral Phosphorus supplementation &amp; calcitriol. Repeat labs showed normalization of Ph 2.4 mg/dl. Audiology evaluation suggested mild sensorineural hearing loss. Heart calcium score was zero. Discussion ENPP1 gene mutation's clinical presentations can vary from no symptoms, hypophosphatemic rickets to death in the first six months of life from generalized arterial calcification. ENPP1 is an enzyme, which degrades ATP into adenosine monophosphate (AMP) and pyrophosphate (PPi). PPI is an inhibitor of hydroxyapatite crystallization in vascular tissue and organs, while Ph is a pro-mineralization factor. ENPP1 gene mutation results in a low concentration of PPi, predisposing the patient to pathological calcification. It is speculated that ENPP-1 modulates FGF-23 secretion. FGF-23 elevation in these patients is a protective response, as hypophosphatemia prevents pathological calcification. Treatment target is to keep phosphate at low end of normal. In our patient, ENPP- 1 mutation likely contributed to recurrent renal stones and possible parathyroid adenoma. Evaluation of genetic mutations is necessary to decide for or against FGF-23 antibody/Burosumab treatment. In ENPP-1 mutation. Burosumab should be avoided as it can bind to FGF-23 resulting in pathological calcification. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Persistently Augmented FGF-23 Serum Values in a Surgically Resolved Oncogenic Osteomalacia Patient with No Tumor and Inflammatory Activity

Objective: Oncogenic osteomalacia is a paraneoplastic syndrome characterized by severe hypophosphatemia, hyperphosphaturia, and osteomalacia subordinated to renal loss of phosphate. It is caused by overproduction of phosphatonin fibroblast growth factor-23 by benign mesenchymal tumors which, when surgically eliminated, returns to basal levels. Methods: We report a case of a patient with oncogenic osteomalacia from a sacrum mesenchymal tumor whose FGF-23 levels remain elevated two years after successful surgical treatment. Results: A 53-year-old man with severe difficulty to walk and stand, severe hypophosphatemia, hyperphosphaturia, and raised levels of alkaline phosphatase and FGF-23 was diagnosed with oncogenic osteomalacia after a thorough process of elimination of causes of hyphosphatemia were excluded. Despite systemic chemotherapy, surgical removal of sacrum, primary mesenchymal tumor, phosphate and calcium supplementation, and no evidence of tumor recurrence, the serum concentration of FGF-23 remains elevated two years after discharge. Conclusions: The possible underlying mechanisms of sustained FGF-23 serum concentrations in this patient suggest the presence of molecular alterations in the FGF/FGFR signaling pathway.

39-Year-Old Woman With Severe Weakness

39-Year-Old Woman With Severe Weakness

Quantitation of phosphohistidine in proteins in a mammalian cell line by 31P NMR.

There is growing evidence to suggest that phosphohistidines are present at significant levels in mammalian cells and play a part in regulating cellular activity, in particular signaling pathways related to cancer. Because of the chemical instability of phosphohistidine at neutral or acid pH, it remains unclear how much phosphohistidine is present in cells. Here we describe a protocol for extracting proteins from mammalian cells in a way that avoids loss of covalent phosphates from proteins, and use it to measure phosphohistidine concentrations in human bronchial epithelial cell (16HBE14o-) lysate using 31P NMR spectroscopic analysis. Phosphohistidine is determined on average to be approximately one third as abundant as phosphoserine and phosphothreonine combined (and thus roughly 15 times more abundant than phosphotyrosine). The amount of phosphohistidine, and phosphoserine/phosphothreonine per gram of protein from a cell lysate was determined to be 23 μmol/g and 68 μmol/g respectively. The amount of phosphohistidine, and phosphoserine/phosphothreonine per cell was determined to be 1.8 fmol/cell, and 5.8 fmol/cell respectively. Phosphorylation is largely at the N3 (tele) position. Typical tryptic digest conditions result in loss of most of the phosphohistidine present, which may explain why the amounts reported here are greater than is generally seen using mass spectroscopy assays. The results further strengthen the case for a functional role of phosphohistidine in eukaryotic cells.

Lambda light chain-induced monoclonal gammopathy of renal significance, manifesting with Fanconi Syndrome and osteomalacia

BackgroundMonoclonal gammopathy of renal significance (MGRS) encompasses a heterogeneous group of kidney diseases in which a monoclonal immunoglobulin secreted by a clone of B cells or plasma cells causes kidney damage without meeting the hematological criteria for malignancy. Among the various forms of involvement, MGRS can manifest as a proximal tubule disorder, such as Fanconi syndrome (FS), characterized by urinary loss of phosphate, glucose, amino acids, uric acid and bicarbonate. Few cases of MGRS have been described in the literature, manifesting as FS and monoclonal production of lambda light chains, almost all of which are secondary to the production of kappa light chains.Case presentationHere we report a clinical case of a 45-year-old Brazilian male, African descent, with proximal weakness of the lower limbs, whose initial assessment showed a urine summary with the presence of proteinuria and glycosuria without hyperglycemia, associated with mild worsening of renal function, hypouricemia, hypocalcemia and phosphaturia. Evolution was characterized by a MGRS manifesting as FS and osteomalacia.ConclusionThe diagnosis of MGRS is not always easy, it requires knowledge of the clinical characteristics, diagnostic criteria and prognosis of each case. Therefore, all possible efforts should be made for multidisciplinary diagnosis.

Articular Manifestations of X-Linked Hypophosphatemic Rickets in Saudi Children: A Retrospective Cohort Study

Introduction: This retrospective cohort study aimed to describe the articular manifestations in Saudi children with X-linked hypophosphatemic rickets (XLHR). Materials and Methods: The medical records of children with XLHR were retrospectively reviewed. The diagnosis of XLHR was confirmed biochemically by low serum phosphorus and elevated alkaline phosphatase, radiologically by the evidence of active rickets and genetically by phosphate-regulating gene with homology to endopeptidases (PHEX) gene mutations. Results: Twenty-two patients with XLHR (10.8 years + 4.9) were enrolled. All children were followed at King Faisal Specialist Hospital &amp; Research Center for a mean duration of 8.7 years (+3.7). Clinically, all patients had disproportionate short stature (-2.5 standard deviation +1.3) with varying degrees of skeletal deformities, including genu varum in 68%, genu valgum in 18%, coxa vara in 14%, bowing of tabia in 32%, and history of fractures in 32% of children. Hearing impairment was noted in two children. Biochemically, all patients showed increased urinary phosphate loss with hypophosphatemia 0.67 mmol/l (+0.15) and elevated serum alkaline phosphatase levels 522 IU/l (+133). Genetically, hemizygous PHEX mutation (C746F) was reported in seven patients. Radiologically, four children had osteoarthritis and three had enthesopathies. Four patients craniosynostosis. All children were on oral inorganic phosphate salts (50–70 mg/kg/day), combined with 1,25(OH)2D3 (alfacalcidol or calcitriol, 30–40 ng/kg/day). Conclusion: Patients with XLHR frequently present with varying degrees of joint deformities that are not completely resolved with either medical or surgical treatment. Long-term skeletal complications of XLHR that present in adults are less common in children and adolescents.

Long-Term Tubular Dysfunction in Childhood Cancer Survivors; DCCSS-LATER 2 Renal Study.

Simple SummaryWe studied survivors of childhood cancer who received cancer treatment that might affect the kidneys and compared them to controls from the general population. We investigated if there was a difference in the occurrence of tubular dysfunction. The tubules are the part of the kidney responsible for reabsorption of needed substances to the blood and the removal of wastes. After around 25 years since their cancer diagnosis, we found that in general there were no differences between survivors and controls, but survivors more often had losses of small proteins in the urine. Yet, some survivors of childhood cancer were found to have an increased risk of tubular dysfunction. Namely, survivors treated with the chemotherapeutic agents ifosfamide, cisplatin or carboplatin. Therefore, these patients should be monitored during their follow-up.The aim of this nationwide cross-sectional cohort study was to determine the prevalence of and risk factors for tubular dysfunction in childhood cancer survivors (CCS). In the DCCSS-LATER 2 Renal study, 1024 CCS (≥5 years after diagnosis), aged ≥ 18 years at study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e., nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation) participated, and 500 age- and sex-matched participants from Lifelines acted as controls. Tubular electrolyte loss was defined as low serum levels (magnesium < 0.7 mmol/L, phosphate < 0.7 mmol/L and potassium < 3.6 mmol/L) with increased renal excretion or supplementation. A α1-microglobulin:creatinine ratio > 1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Multivariable risk analyses were performed. After median 25.5 years follow-up, overall prevalence of electrolyte losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls. LMWP was more prevalent (CCS 20.1% versus controls 0.4%). LMWP and magnesium loss were associated with glomerular dysfunction. Ifosfamide was associated with potassium loss, phosphate loss (with cumulative dose > 42 g/m2) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m2 with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m2 was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors.

Enfermedades metabólicas óseas: osteomalacia

The term osteomalacia traditionally refers to a characteristic skeletal disease that is documented radiologically or histologically, not just the clinical or biochemical abnormalities. Osteomalacia is currently defined as a mineralization defect in the recently formed bone matrix, leading to accumulation of osteoid. The principal causes of osteomalacia are a vitamin D disorder, renal phosphate loss, or uncommon causes related to a direct abnormality in the mineralization process.Osteomalacia causes greater bone fragility, with the appearance of spontaneous fissures or fractures. Although it is an uncommon entity, it should be suspected when faced with symptoms of diffuse osteoarticular pain. In very advanced forms, an X-ray will show biconcave vertebrae or long bone deformity with pseudofractures or Looser's zones. A transiliac crest bone biopsy with double tetracycline labeling and its histomorphometric evaluation is the most precise way of diagnosing osteomalacia. However, it is not usually performed in clinical practice as it is an invasive technique. Therefore, a diagnosis tends to be made based on a combination of clinical and laboratory data and radiological findings. The treatment is what is indicated for the underlying pathology that triggered the osteomalacia, although vitamin D supplementation may be considered the essential pillar of therapy.

Electrochemical Deoxygenative Barbier-Type Reaction.

An effective deoxygenative C(sp3)-C(sp3) bond formation reaction is achieved through electrochemical reduction of alcoholic phosphates or sulfonates with aldehydes or ketones. Alcohol derivatives of phosphates undergo single-electron reduction under electrochemical conditions followed by a spontaneous cleavage of the C-O bond with the exothermic loss of phosphate resulting in an alkyl radical species. Subsequently, radical intermediates are further reduced to carbanions at the cathode, which are in situ trapped by carbonyl compounds, thus accomplishing a deoxygenative Barbier-type reaction.

Evaluation of proximal tubule functions in children with COVID-19: a prospective analytical study.

BackgroundThere are limited numbers of studies focusing on renal effects of coronavirus disease 2019 (COVID-19) infection and proximal tubular dysfunction in children with COVID-19 infections. The purpose of this study was to evaluate the functions of the proximal tubule in hospitalized children with confirmed acute COVID-19.MethodsThe children who were hospitalized for confirmed COVID-19 were included in this prospective descriptive analysis. The presence of at least two of the following four abnormalities was used to diagnose proximal tubule injury: abnormal tubular reabsorption of phosphate, normoglycemic glycosuria, hyperuricosuria, and proteinuria.ResultsA total of 115 patients were included in the study. About a third of the individuals had elevated blood creatinine levels or proteinuria. In addition, abnormal renal tubular phosphate loss measured by renal tubular phosphate loss was found in 10 (8.7%) patients, as was hyperuricosuria in 28.6%. As a result, total proximal tubular dysfunction was found in 24 (20.9%) patients.ConclusionsOne in every five children with acute COVID-19 infections had proximal tubular dysfunction, according to our data. Although, the rate of proximal tubular dysfunction was lower than in adults, it should be noted. The recovery of proximal tubular function in children with COVID-19 should be followed.

Comparative Evaluation of Influence of Nd:YAG Laser (1064 nm) and 980 nm Diode Laser on Enamel around Orthodontic Brackets: An In Vitro Study.

(1) Background: The prevention of demineralizing lesions at the enamel structure level continues to represent a challenge in daily dental practice. When bacteria influence the pH level, this will decrease below the threshold for remineralization and the dissociation of hydroxyapatite will occur with a high percentage of phosphate and calcium loss. These elements continue to be studied by many authors in order to obtain a working protocol that will lead to their stabilization at the level of the enamel structure, thus preventing the demineralization process. The aim of this study is to evaluate and compare the influence of two types of laser wavelengths on the surface morphology and mineral components of the enamel through an examination with scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDX). (2) Methods: Thirty permanent human incisors extracted for periodontal reasons from patients aged 25–40 years old were selected for this study. Metallic brackets (SS Standard 022 Slot, OC Orthodontics, McMinnville, OR, 97128, USA) were bonded onto each tooth. The buccal surface was randomly assigned three sections: Section A—negative control (no treatment), section B—treated with 980 nm Gallium–Aluminum–Arsenide diode laser (a 300 µm optic fiber was used with 0.8 W output power, energy density of 5.33 J/mm2, in continuous mode, for 30 s, oriented perpendicularly to the enamel surface in contact mode) (KaVo GENTLEray 980 Diode Laser, Kaltenbach & Voigt GmbH, Biberach, Germany), and section C—treated with Nd:YAG laser (a 300 µm fiber was carried out at a 1 mm distance from the enamel surface with 0.75 W power, 75 mJ pulse energy, pulse repetition rate of 10 Hz, 5 J/mm2 fluency, average exposure time of 30 s, and water cooling assisted) (LIGHTWALKER AT S, M021-5AF/1 S, Fotona d.o.o, Ljubljana, Slovenia). The elements evaluated in this study were calcium (Ca), phosphate (P), oxygen (O), and carbon (C). A one-way analysis of variance, paired t-tests, and independent t-tests were carried out to evaluate the results using the SPSS 19 IBM Statistical package software for Microsoft. (3) Results: The evaluation of the data indicated that both wavelengths produced an increase in Ca wt% (for diode laser the mean of Ca wt% before irradiation was 21.06, while that after treatment reached 28.24; and for Nd:YAG laser, the mean of Ca wt% before irradiation was 21.31, while that after treatment reached 33.88); as well, the 980 nm diode laser decreased P wt% (from 17.20 before irradiation to 16.92 after irradiation) and the Nd:YAG laser increased P wt% (from 17.46 before irradiation to 18.28 after irradiation). These results showed a statistically significant difference at the p < 0.05 level. (4) Conclusions: It can be concluded that the best improvement of enamel chemical composition was obtained with Nd:YAG irradiation.

Vitamin D and Phosphate Interactions in Health and Disease.

Vitamin D plays an essential role in calcium and inorganic phosphate (Pi) homeostasis, maintaining their optimal levels to assure adequate bone mineralization. Vitamin D, as calcitriol (1,25(OH)2D), not only increases intestinal calcium and phosphate absorption but also facilitates their renal reabsorption, leading to elevated serum calcium and phosphate levels. The interaction of 1,25(OH)2D with its receptor (VDR) increases the efficiency of intestinal absorption of calcium to 30-40% and phosphate to nearly 80%. Serum phosphate levels can also influence 1,25(OH)2D and fibroblast growth factor 23 (FGF23) levels, i.e., higher phosphate concentrations suppress vitamin D activation and stimulate parathyroid hormone (PTH) release, while a high FGF23 serum level leads to reduced vitamin D synthesis. In the vitamin D-deficient state, the intestinal calcium absorption decreases and the secretion of PTH increases, which in turn causes the stimulation of 1,25(OH)2D production, resulting in excessive urinary phosphate loss. Maintenance of phosphate homeostasis is essential as hyperphosphatemia is a risk factor of cardiovascular calcification, chronic kidney diseases (CKD), and premature aging, while hypophosphatemia is usually associated with rickets and osteomalacia. This chapter elaborates on the possible interactions between vitamin D and phosphate in health and disease.