Blood Phosphate Research Articles

Evaluation of fasting impact during Ramadan month on patients with a history of kidney stones in a military hospital

Introduction: One of the cornerstones and common causes of kidney stone formation is the volume of fluid consumed during a 24- hour that influences on forming that by several mechanisms. Since fluid intake decreases during Ramadan, one of the common questions posed is whether Ramadan fasting is associated with the precipitating of stone formation. The present study was aimed to investigate the effect of Ramadan fasting on precipitating and Inhibitors of stone formation in patients with a history of renal kidney disease. Methods: The study population included all of the patients with kidney stone diseases who were seen at the Clinic of Urology and Nephrology affiliated with Baqiyatallah hospital during the month of Ramadan in 2014 and 2015. The number of 66 patients was chosen and included in the study through randomized simple sampling. All subjects underwent blood tests like serum uric acid, serum phosphate, serum calcium, and serum sodium. Samples were tested in terms of volume, magnesium, uric acid, Calcium, Phosphate, Sodium, citrate, oxalate, Calcium oxalate supersaturation, Calcium Phosphate supersaturation, Uric acid supersaturation. Results: Sixty-six eligible patients were included that the mean age was 48.35±12.10 years. Fourteen men and 52 women were included. There were no significant differences in the mean pH of urine, urinary sodium, urinary oxalate, supersaturated levels of calcium oxalate in the urine, urinary phosphate levels, and super-saturated levels of urinary calcium phosphate between the two groups (P>0.05). The average volume of urine, urinary magnesium, urinary calcium, urinary citrate, the uric acid level in the non-fasting group was higher than the fasting group (P<0.05). There were no differences in the average blood calcium levels, blood sodium, blood phosphate levels, blood acidic levels between the two groups (P>0.05). There was no difference in the mean super-saturated level of uric acid between the two groups (P=0.035). Conclusion: There was controversial evidence on the effect of Ramadan fasting on kidney stone formation and there is not enough evidence in the present study that Ramadan fasting precipitates risk factors associated with calculus formation.

Controlling the self-assembly of human calcitonin: a theoretical approach using molecular dynamics simulations.

Human calcitonin (hCT) is a 32-residue amino acid poly-peptide hormone which is secreted by the C-cells (also known as parafollicular cells) of thyroid glands. It acts to inhibit osteoclast cell hormones by reducing the cell function and regulating calcium and phosphate in blood. hCT has a high tendency to assemble into protofilaments with β-sheet conformations. Amyloid fibril formation of hCT reduces its bio-activity and limits its application as a therapeutic drug. Salmon calcitonin (sCT), which also carries the same disulfide bridge at the N and C-terminus, but differs at the 16 residue position from hCT, has less propensity to aggregate than hCT. Human calcitonin has much higher bio-activity than sCT if its aggregation propensity is reduced. Substituting the key residues which are responsible for the aggregation of hCT, is one of the ways to reduce its aggregation and fibril formation. hCT analogues with less aggregation tendency can be exploited as therapeutic drugs. In this work, we study the amyloidogenic behavior of hCT and its peptide based derivatives i.e., sCT, phCT, N17H hCT, Y12L hCT and DM hCT, through classical molecular dynamics (MD) simulations. Our study reveals that sCT is the least aggregation prone derivative, and the double mutation at position 12 and 17 can reduce the aggregation propensity of this peptide. Also, we have applied these mutant variants of hCT as peptide inhibitors in the self-aggregation of hCT. This study could help in understanding and preparing peptide-based inhibitors for hCT fibrillation and their applications as therapeutic drugs.

Body composition and cardiometabolic health of pediatric patients with X-linked hypophosphatemia (XLH) under burosumab therapy.

Background:Burosumab, a recombinant anti-FGF23 monoclonal antibody, was recently introduced as a treatment for X-linked hypophosphatemia (XLH). Burosumab normalizes blood phosphate levels, thereby healing rickets, decreasing leg bowing, and reducing pain. We aimed to explore the body composition and cardiometabolic health of pediatric patients with XLH treated with burosumab.Methods:This observational real-life study was conducted on growing children and adolescents. The outcome measures included changes in sex- and age-adjusted anthropometric and body composition parameters [fat mass (FM), fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), muscle-to-fat ratio (MFR)], blood pressure, laboratory evaluation, and radiographic rickets severity [Thacher Rickets Severity Score (TRSS)]. Body composition was assessed by bioelectrical impedance analysis (BIA). Percentiles for FFM% and ASMM% were calculated according to BIA pediatric reference curves. The delta variable was calculated as the variable at 12 months minus the variable at baseline.Results:A total of 15 pediatric patients with XLH are treated in our clinic; included in the analyses were 7 children and adolescents (3 males, mean age 8.7 ± 3.2 years) with XLH without comorbidities. Baseline BIA revealed an unfavorable physique, with increased body fat percentage in five patients and decreased muscle mass in six. Indices of lean body mass significantly increased after 6 and 12 months of treatment: FFM(kg) (p = 0.001, p = 0.046, respectively) and ASMM(kg) (p = 0.012, p = 0.034, respectively), without any significant change in FM(kg). The percentile of ASMM% increased significantly after 6 months of treatment (p = 0.006) and stabilized thereafter. TRSS improved significantly after 12 months of therapy (p = 0.005). Age was positively correlated with delta TRSS (r = 0.814, p = 0.026), and delta TRSS was negatively correlated with delta MFR (r = −0.826, p = 0.022).Conclusions:There was a heretofore unrecognized improvement in body composition of growing children and adolescents with XLH who were treated with burosumab. These findings highlight the need to initiate burosumab treatment at a younger age when rickets is less severe.

Prevalence of hypophosphatemia in the ICU – Results of an international one-day point prevalence survey

Hypophosphatemia (HypoP) is associated with organ dysfunction and mortality. Despite its potential severe consequences, HypoP remains poorly characterized in terms of real prevalence and timing of onset. The primary objective was to determine the prevalence of HypoP defined as blood phosphate <0.8 and<0.65mmol/l on one particular day at international level. One-day point prevalence survey conducted by the Section of Metabolism, Endocrinology and Nutrition (MEN) of the European Society of Intensive Care Medicine (ESICM) during week 11-2020. In total, 56 adult and 4 paediatric ICUs, from 22 countries participated: 41 ICUs were mixed medico surgical, the 19 others being cardiac, medical or surgical. Phosphate measurements were performed daily in 21 ICUs, and 1-3 times per week in 39 ICUs. On D-Day 909 patients (883 adults) were present and 668/883 (75.7%) had serum/plasma phosphate determined, revealing a HypoP in 103 (15.4%) patients aged 62 [18 to 85] years. Of those, 49 patients presented phosphate <0.65mmol/l: cases of hypophosphatemia were detected at any time of patient's ICU stay. No HypoP was observed in children. A treatment protocol existed only in 41.1% of adult ICUs, independently of ICU type, or size. Only 41/98 of the HypoP patients (29/41 of patients with phosphate <0.65mmol/l) were receiving phosphate. HypoP is present at least in 15.4% of ICU patients, and may occur at any time during the ICU stay. The absence of phosphate repletion protocols in 60% of participating ICUs is an unexpected finding, and confirms the necessity for the development of ICU phosphate protocols and guidelines. NCT04201899.

Safety and pharmacokinetics of a biosimilar of denosumab (KN012): Phase 1 and bioequivalence study in healthy Chinese subjects

ABSTRACT Background KN012 is a proposed biosimilar candidate for the reference drug denosumab, with the brand name Prolia®. This study explored the tolerance, variability, and pharmacokinetics (PK) of denosumab and its biosimilar in healthy Chinese subjects. Research design and methods A randomized, double-blind, parallel, two-arm study was performed to analyze the bioequivalence of denosumab biosimilar (60 mg) compared with denosumab. Results The PK properties of denosumab biosimilar were similar to those of denosumab. When denosumab biosimilar was compared to denosumab, the geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ were 98.74%, 102.54%, and 102.18%, respectively, and the 90% confidence interval was observed to be within 80–125%. The inter-subject variability ranged from 31.4% to 34.6%. Five subjects in the denosumab biosimilar group and one subject in the denosumab group were positive for anti-drug antibodies (ADAs) and negative for neutralizing antibodies (NAbs). Adverse reactions were observed in 100% (52 subjects) and 94.0% (47 subjects) of the subjects in the denosumab biosimilar and denosumab groups, respectively. Reductions in the blood calcium and phosphate levels were the most common adverse reactions. Conclusion The PK characteristics were comparable for the denosumab biosimilar and denosumab groups. Their safety profiles were also similar. Trial Registration : The trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html #CTR20181231).

PTH and FGF23 Exert Interdependent Effects on Renal Phosphate Handling: Evidence From Patients With Hypoparathyroidism and Hyperphosphatemic Familial Tumoral Calcinosis Treated With Synthetic Human PTH 1-34.

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) both influence blood phosphate levels by regulating urinary phosphate reabsorption. Clinical data suggest that adequate renal phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, which features high blood phosphate in spite of concomitant FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting hyperphosphatemia, were treated with synthetic human PTH 1-34 (hPTH 1-34). Biochemical parameters, including blood phosphate, calcium, intact FGF23 (iFGF23), nephrogenic cAMP, 1,25(OH)2 vitamin D (1,25D), and tubular reabsorption of phosphate (TRP), were measured at baseline and after hPTH 1-34 treatment. In patients with hypoparathyroidism, administration of hPTH 1-34 increased nephrogenic cAMP, which resulted in serum phosphate normalization followed by a significant decrease in iFGF23. TRP initially decreased and returned to baseline. In the patient with HFTC, hPTH 1-34 administration also increased nephrogenic cAMP, but this did not produce changes in phosphate or TRP. No changes in calcium were observed in any of the studied patients, although prolonged hPTH 1-34 treatment did induce supraphysiologic 1,25D levels in the patient with HFTC. Our results indicate that PTH and FGF23 effects on phosphate regulation are interdependent and both are required to adequately regulate renal phosphate handling. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

Comparison of Hematological and Biochemical Results Derived from Arterial and Venous Blood Samples in Post-Anesthetic Dogs.

Simple SummaryIn contrast to humans, general anesthesia is required for both surgical procedures and diagnostic imaging like magnetic resonance imaging (MRI) and computed tomography (CT) in small animals. Because the post-anesthetic period is a particularly high risk time for death, serial monitoring of biochemical and hematological parameters could be required. Blood samples could be collected from an indwelling arterial catheter to avoid stress caused by venipuncture, but studies using arterial blood for hematological and biochemical testing have been limited. The aim of this study is to compare hematological and biochemical results derived from venous and arterial blood samples, and to evaluate their clinical interchangeability in post-anesthetic dogs. We found statistically significant but clinically irrelevant differences in hemoglobin, glucose, creatinine, and calcium levels, and results from venous and arterial blood samples are not clinically interchangeable for gamma-glutamyl transpeptidase and potassium levels.Collecting blood from an indwelling arterial catheter may reduce stress from repeated venipuncture in patients requiring serial monitoring, but the use of arterial blood for hematological and biochemical testing remains understudied. Here, we compared hematological and biochemical results of arterial and venous blood and evaluated their clinical interchangeability. Blood samples from dogs who had recovered from anesthesia, collected by both arterial catheterization and venipuncture, were analyzed. To assess clinical acceptance between paired samples, the limit of agreement between the values derived from the arterial and venous blood samples was compared with the allowable total error (TEa) recommended for each parameter. We found no significant differences between the arterial and venous sample results for red/white blood cell and platelet counts and hematocrit, blood urea nitrogen, phosphate, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin, sodium, potassium, and chloride levels, whereas hemoglobin, glucose, creatinine, and calcium levels differed significantly (p < 0.05). Moreover, only gamma-glutamyl transpeptidase and potassium exceeded the recommended TEa. Hematological and biochemical results derived from venous and arterial blood samples are clinically interchangeable in post-anesthetic dogs, with the exception of gamma-glutamyl transpeptidase and potassium; thus, these values should be used with caution.

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

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

Effects of loach skin collagen peptides in reducing osteoporosis in mice

• LCP or the combination of LCP and sodium selenite alleviated osteoporosis of mice through Wnt/β-catenin pathway. • LCP or the combination of LCP and sodium selenite alleviated osteoporosis of mice through OPG/RANKL/NF-kB pathway. • LCP or the combination of LCP and sodium selenite increase bone biomechanical properties of mice. The effects of loach skin collagen peptides (LCP) and the combination of LCP and sodium selenite on osteoporosis in mice were investigated. The results showed that the combination of LCP and sodium selenite alleviated mice osteoporosis induced by retinoic acid. It improved bone microarchitecture, increased the number and mass of trabecular bone, maintained blood calcium and phosphate balance in mice. The combination of LCP and sodium selenite inhibited the relative mRNA expression levels of Wnt10, β-catenin, osteogenic transcription factors Runx2 and Osterix through the Wnt/β-catenin pathway. The ratio of receptor activator for nuclear factor-kB ligand/Osteoprotegerin (RANKL/OPG) was down-regulated through the OPG/RANKL/NF-kB pathway. Likewise, the relative mRNA expression levels of tumor necrosis factor receptor associated factor 6 (TRAF6), nuclear factor kB (NF-kB) and nuclear factor of activated T-cell (NFATC1) were reduced. This study provides useful information for the use of LCP and sodium selenite in treating and reduction of osteoporosis.

Independent Predictors of In-Hospital Mortality in Patients with COVID-19 in London, United Kingdom: An Observational Cohort Study

Background: Coronavirus disease 2019 (COVID-19) has rapidly evolved as a global health crisis, the majority of patients affected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will present with mild symptoms, respiratory disease and acute respiratory distress syndrome (ARDS) has been widely reported as one of the most common features of COVID-19. Although many studies have reported the demographics, clinical presentations, and outcomes in COVID-19 all over the world, studies with a large population affected with COVID-19 from the UK are still limited. Therefore, the aim of the study was to describe demographics, baseline clinical characteristics, comorbidities, and outcomes, and furthermore identify risk factors of in-hospital mortality using a large observational study cohort of COVID-19 patients in a busy hospital in London, UK. Methods: We analyze 393 consecutive hospitalized patients with confirmed COVID-19 admitted to Queen Elizabeth Hospital, London from March 12, 2020 to April 18, 2020. Demographics, clinical presentations, laboratory tests, radiological assessments, and in-hospital outcomes were collected and analyzed. Univariate analysis and multivariate Cox regression were performed to determine independent predictors of in-hospital mortality. Findings: In our cohort, 393 patients with COVID-19 were identified (mean age, 67.5 years; 59% males). The majority of patients were Caucasian (66.9%) and most common signs were cough (49.9%), fever (46.8%), and dyspnea (46.1%). A total of 161 (40.9%) of patients died within 30 days of admission. The average age in the non-survival group was older than that in the survival group (75.2 vs. 62.2 years old, qInterpretation: This case series provides valuable insights into clinical characteristics and independent risk factors of mortality in hospitalized patients with confirmed COVID-19 within the UK health care system. We are the first to report that hypernatremia is an independent predictor of mortality in COVID-19 patients. Funding: This work was supported by the funding to Yao through the Chinese Postdoctoral Science Foundation (2019M663271) and the Chinese Scholarship Council (201808440461).Declaration of Interests: N/AEthics Approval Statement: The study was approved as a minimal-risk research using data that had already been collected for patients as part of their normal care, was not an interventional study and waived the requirement for informed consent.

Nutrition and Micronutrient Therapy in Critical Illness Should Be Individualized.

Critically ill (intensive care unit [ICU]) patients are characterized by organ failure, intense inflammatory response, insulin resistance, and altered metabolic response. The sicker the patient, the higher the threat to nutrition and micronutrient status. In addition, many patients start the ICU stay with an altered nutrition status, which requires assessment upon admission. Nutrition needs vary among patients as well as during hospitalization, as the metabolic response changes over time. Shock and acute organ failure result in a metabolic shift toward intense catabolism: endogenous glucose production aiming at ensuring the basal adenosine triphosphate production starts immediately and occurs at the expense of the lean body mass using amino acids for neoglucogenesis. Later, the stabilization and recovery phases are characterized by higher energy and substrate needs. Indirect calorimetry is the only tool enabling determination of the metabolic level. When and how should feeding be started? Recent research shows that the route does not matter much, with equipoise between enteral and parenteral nutrition (PN) as long as overfeeding is avoided. As micronutrients are an integral part of metabolism and antioxidant defenses, their delivery must be ensured: whereas needs are well defined for healthy individuals, needs for illness remain poorly defined. PN that contains only macrosubstrates requires the daily prescription of multimicronutrient complements to qualify as total PN. Achievement of goals requires minimal monitoring, consisting of the daily verification of energy and protein goal delivery achievement and daily follow-up determining blood glucose and phosphate levels and insulin requirements.

Predicting the risk of severe myocardial infarction in patientswith chronic 5D-stage kidneydisease and mineral-bone disorders

BACKGROUND. The increasing prevalence of chronic kidney disease is a global trend as well in general as in terminal kidney failure in particular. Of great interest is the analysis of the impact of mineral and bone disorders on the risk of cardiovascular complications and, first of all, acute myocardial infarction (AMI ). THE AIM: to assess the impact of bone mineral disorders on the risk of AMI in patients with stage 5D chronic kidney disease. PATIENTS AND METHODS. It was conducted a prospective (three-year) cohort study of 85 patients with CKD S5D treated with programmed hemodialysis. At the first stage, it were reg­istered the risk factors and clinical manifestations of CKD 5 St, as well as indicators that characterized bone mineral disorders (levels of blood inorganic phosphate, calcium, parathyroid hormone, 1,25(OH)D, fibroblast growth factor (FGF-23), a-Klotho). Signs of calcification of the heart valves and aortic wall were also determined. The second stage involved a re-examination of patients after 3.1±0.1 years, as well as registration of endpoints, which were identified as cases of fatal and non-fatal AMI. RESULTS. After 3 years of follow-up, the following endpoints were registered: nonfatal AMI - 6 cases, fatal AMI-4 cases. The risk of AMI increased in the presence of initial persistent hyperphosphatemia and 1,25(OH)D3 deficiency, as well as calcifica­tion of heart valves and high FGF-23 values, but only in combination with hyperphosphatemia and 1,25(OH)D3 deficiency. Hyperparathyroidism also increased the risk of AMI in conditions of a deficit of 1,25(OH)D3. The risk of nonfatal AMI cases was also increased by the presence of aortic calcification and its severity. The risk of AMI increases in the presence of initial persistent hyperphosphatemia and a deficit of 1.25 (OH)D3, as well as CCS, high FGF-23 values, but only in combination with hyperphosphatemia and a deficit of 1.25(OH)D3. Hyperparathyroidism also increases the risk of AMI in conditions of a deficit of 1.25(OH)D3. The risk of nonfatal cases of AMI also increases the presence of aortic calcification and its severity. CONCLU­SION. The risk of AMI increases in the presence of initial persistent hyperphosphatemia and a deficit of 1,25(OH)D3, as well as calcification of the heart valves, high FGF-23 values, but only in combination with hyperphosphatemia and a deficit of 1,25(OH) D3. Hyperparathyroidism also increases the risk of AMI in conditions of a deficit of 1.25(OH)D3. The risk of nonfatal cases of AMI also increases the presence of aortic calcification.

Osteocytic FGF23 and Its Kidney Function.

Osteocytes, which represent up to 95% of adult skeletal cells, are deeply embedded in bone. These cells exhibit important interactive abilities with other bone cells such as osteoblasts and osteoclasts to control skeletal formation and resorption. Beyond this local role, osteocytes can also influence the function of distant organs due to the presence of their sophisticated lacunocanalicular system, which connects osteocyte dendrites directly to the vasculature. Through these networks, osteocytes sense changes in circulating metabolites and respond by producing endocrine factors to control homeostasis. One critical function of osteocytes is to respond to increased blood phosphate and 1,25(OH)2 vitamin D (1,25D) by producing fibroblast growth factor-23 (FGF23). FGF23 acts on the kidneys through partner fibroblast growth factor receptors (FGFRs) and the co-receptor Klotho to promote phosphaturia via a downregulation of phosphate transporters, as well as the control of vitamin D metabolizing enzymes to reduce blood 1,25D. In the first part of this review, we will explore the signals involved in the positive and negative regulation of FGF23 in osteocytes. In the second portion, we will bridge bone responses with the review of current knowledge on FGF23 endocrine functions in the kidneys.

Tumour induced osteomalacia: a diagnostic challenge and its implications in orthopaedic surgery

&lt;p class="abstract"&gt;Tumor-induced osteomalacia (TIO) is a paraneoplastic phenomenon which encompasses a wide array of clinical features ranging from musculoskeletal pain to pathological fractures. An excess of fibroblast growth factor 23 (FGF23) is produced which is a parahormone with its target receptors in proximal convoluted tubules of glomeruli. This results in decreased blood phosphate levels and decreased hydroxylation of 25-OH vitamin-D, ultimately leading to osteomalacia. Compliance with medical treatment is unsatisfactory and tedious owing to repeated dosing schedules and overwhelming side effects. Surgical excision of the lesion is the only suitable treatment.&lt;/p&gt;

Nephropathic Cystinosis: A Distinct Form of CKD-Mineral and Bone Disorder that Provides Novel Insights into the Regulation of FGF23.

The rare lysosomal storage disease nephropathic cystinosis presents with renal Fanconi syndrome that evolves in time to CKD. Although biochemical abnormalities in common causes of CKD-mineral and bone disorder have been defined, it is unknown if persistent phosphate wasting in nephropathic cystinosis is associated with a biochemical mineral pattern distinct from that typically observed in CKD-mineral and bone disorder. We assessed and compared determinants of mineral homeostasis in patients with nephropathic cystinosis across the predialysis CKD spectrum to these determinants in age- and CKD stage-matched patients, with causes of CKD other than nephropathic cystinosis. The study included 50 patients with nephropathic cystinosis-related CDK and 97 with CKD from other causes. All major aspects of mineral homeostasis were differentially effected in patients with CKD stemming from nephropathic cystinosis versus other causes. Patients with nephropathic cystinosis had significantly lower percent tubular reabsorption of phosphate and fibroblast growth factor-23 (FGF23) at all CKD stages, and lower blood phosphate in CKD stages 3-5. Linear regression analyses demonstrated lower FGF23 levels in nephropathic cystinosis participants at all CKD stages when corrected for eGFR and age, but not when adjusted for serum phosphate. Nephropathic cystinosis CKD patients have mineral abnormalities that are distinct from those in CKD stemming from other causes. Persistently increased urinary phosphate excretion maintains serum phosphate levels within the normal range, thus protecting patients with nephropathic cystinosis from elevations of FGF23 during early CKD stages. These findings support the notion that phosphate is a significant driver of increased FGF23 levels in CKD and that mineral abnormalities associated with CKD are likely to vary depending on the underlying renal disease.

Route of intestinal absorption and tissue distribution of iron contained in the novel phosphate binder ferric citrate.

Anemia of chronic kidney disease (CKD) is, in part, caused by hepcidin-mediated impaired iron absorption. However, phosphate binder, ferric citrate (FC) overcomes the CKD-induced impairment of iron absorption and increases serum iron, transferrin saturation, and iron stores and reduces erythropoietin requirements in CKD/ESRD patients. The mechanism and sites of intestinal absorption of iron contained in FC were explored here. Eight-week old rats were randomized to sham-operated or 5/6 nephrectomized (CKD) groups and fed either regular rat chow or rat chow containing 4% FC for 6 weeks. They were then euthanized, and tissues were processed for histological and biochemical analysis using Prussian blue staining, Western blot analysis to quantify intestinal epithelial tight junction proteins and real-time PCR to measure Fatty Acid receptors 2 (FFA2) and 3 (FFA3) expressions. CKD rats exhibited hypertension, anemia, azotemia, and hyperphosphatemia. FC-treated CKD rats showed significant reductions in blood pressure, serum urea, phosphate and creatinine levels and higher serum iron and blood hemoglobin levels. This was associated with marked increase in iron content of the epithelial and subepithelial wall of the descending colon and modest iron deposits in the proximal tubular epithelial cells of their remnant kidneys. No significant difference was found in hepatic tissue iron content between untreated and FC-treated CKD or control groups. Distal colon's epithelial tight Junction proteins, Occludin, JAM-1 and ZO-1 were markedly reduced in the CKD groups. The FFA2 expression in the jejunum and FFA3 expression in the distal colon were significantly reduced in the CKD rats and markedly increased with FC administration. Iron contained in the phosphate binder, FC, is absorbed by the distal colon of the CKD animals via disrupted colonic epithelial barrier and upregulation of short chain fatty acid transporters.

Interferences in the measurement of circulating phosphate: a literature review.

Background Inorganic phosphate in blood is currently determined by the reaction with molybdate. This report aims at reviewing conditions underlying spuriously altered levels of circulating inorganic phosphate. Content A systematic search of the Excerpta Medica, the National Library Database and the Web of Science database was conducted without language restriction from the earliest publication date available through January 31, 2020. Summary For the analysis, 80 reports published in English (n = 77), French (n = 1), German (n = 1) and Spanish (n = 1) were retained. Well-documented pseudohyperphosphatemia was observed in individuals exposed to liposomal amphotericin, in patients affected by a gammopathy, in patients with hyperlipidemia and in patients with hyperbilirubinemia. An unexplained elevated inorganic phosphate level sometimes provided a clue to the diagnosis of a gammopathy. Well-documented cases of pseudohypophosphatemia were observed in patients on large amounts of intravenous mannitol. Finally, pseudohypophosphatemia was occasionally observed on treatment with liposomal amphotericin and in patients with a gammopathy. Outlook In order to avoid unnecessary testing and treatment, the phenomenon of spuriously altered inorganic phosphate should be recognized. An unexplained hyperphosphatemia may provide a clue to the diagnosis of a gammopathy or a severe hyperlipidemia.

P1155REMOVAL OF PHOSPHATE AND CREATININE DURING PD WITH DIFFERENT GLUCOSE CONCENTRATIONS

Abstract Background and Aims Adequate removal of creatinine and phosphate is one of the key objectives in peritoneal dialysis (PD). Whereas the mechanism of creatinine removal is well known, there are gaps in understanding regulation of phosphate removal. Clinical studies show that although the size of both molecules is similar, their removal might behave differently (Badve et al CJASN 2008). Several, but not all, studies have suggested that peritoneal phosphate clearance is larger when using CAPD than APD prescriptions, suggesting the dwell time or duration is an important determinant of phosphate clearance. The aim of the study was to investigate specifically the effect of dwell duration at the level of single PD exchange with different glucose concentrations on peritoneal phosphate clearance. Method A prolonged 8-hour PET was carried out in 32 clinically stable PD patients with each of three glucose-based solutions: 1.36% (G1), 2.27% (G2), and 3.86% (G3) with temporary drainage at 1 and 4 hours of peritoneal dwell. Dialysate and blood samples were taken to measure infused and drained volume and concentration of phosphate and creatinine in dialysate and blood. Clearances were calculated for a single exchange for each solution and for 4-hour (4H) and 8-hour (8H) dwell periods. For each patient, the 4-hour creatinine D/P ratio for G3 was calculated. The clearance ratio, ClR, defined as the ratio of solute clearance for particular solution to its clearance for the G1 solution, was calculated for both solutes and each solution and dwell durations. Results The obtained values of 4H creatinine D/P ratio for G3 solution were 0.67±0.11 (mean±SD). The values of solute clearances per single exchange expressed in mL/min, are presented in table below. Creatinine and phosphate clearances were found to be solution and dwell duration dependent with p&amp;lt;0.001. The clearances of both solutes were correlated for the same dwell duration or solution (not for creatinine G2 for 4H vs 8H) with p&amp;lt;0.05. Moreover, solute clearances were also correlated with creatinine D/P for 4H but not for 8H. The clearances of phosphate were also correlated with that for creatinine each solution at both dwell durations with p&amp;lt;0.001. Both calculated ClR were found to be dependent on the solution (p&amp;lt;0.001) but not dwell duration. Similar dependence on solution and correlations are valid in one analyze solute mass removal. Conclusion Phosphate and creatinine clearances were found to be well correlated during a long, 8-hour PET proving similarities in their transport. Interestingly, the dependence of both clearances and ClR on solution glucose concentration suggest that the removal of phosphate as well as creatinine depends on the ultrafiltration induced by glucose concentration in dialysis solution.

P1082COMPARISON OF THE REMOVAL OF PROTEIN-BOUND TOXINS AND LARGE MIDDLE MOLECULES WITH HIGH-FLUX PMMA AND MEDIUM CUT-OFF DIALYZERS

Abstract Background and Aims Dialytic clearance of protein-bound toxins and large middle molecules is poor by diffusive treatment and limited by high-flux hemodialysis (HD) and on-line hemodiafiltration (OL-HDF), and only a few studies have examined how to improve their removal by other extracorporeal strategies. Since 2017, there is a new generation of polymethyl methacrylate (PMMA) membranes that suppress platelet adhesion on the membrane surface improving hemocompatibility and permeability, while also maintaining adsorption properties related to conventional PMMA membranes. Expanded HD (HDx) with medium cut-off (MCO) membranes has also recently been incorporated into clinical practice and may improve the removal of uremic toxins in HD treatments. The aim of this pilot study was to compare the efficacy of a new high-flux PMMA dialyzer (Filtryzer® NF-2.1H) in a post-dilution OL-HDF session with a new MCO membrane (Theranova® 400) in a HDx session. Method In an open, cross-over, single-center, controlled, prospective clinical study, 40 adult stable HD patients were assigned to be treated by post-dilution OL-HDF with the NF-2.1H dialyzer or by HDx with the Theranova 400 dialyzer. All other dialysis parameters, including blood and dialysate flow rates, length of dialysis session, and ultrafiltration rate remained unchanged during both sessions. P-cresyl sulfate (PCS), indoxyl sulfate (IS), and kappa (κ) and lambda( λ) free light chains (FLC) reduction rates were intraindividually compared for the two dialyzer types (primary outcomes). Secondary outcomes included the kt and the reduction ratio of blood urea nitrogen, phosphate and β2 -microglobulin (β 2-m). Results The reduction ratio of protein-bound toxins ranges from 60% to 67%, with no differences between membranes (Figure). PMMA membrane achieved greater FLC reduction ratios than MCO membrane, reaching significance for λFLC (56.6% vs. 77.4%; p &amp;lt; 0.001). Conversely, β2M reduction ratio was slightly but significantly higher with MCO membrane (68.5 vs. 72.1%; p = 0.002). Small molecules removal including urea and phosphate were similar in both groups, achieving an optimal Kt with no differences between groups (61.3±9.2 Vs. 59.7±9.3; p=0.16). Albumin reduction ratio tended to be higher with PMMA membrane without reaching significance (10.1±5.9% Vs. 7.8±12.3%; p=0.17). The mean convective volume achieved with PMMA was 23.5±4.4 L. Conclusion This study suggested that new high-flux PMMA dialyzer in post-dilution OL-HDF mode might achieve better FLC reduction ratios than MCO dyalizer in HDx mode, whereas both techniques may equally remove protein-bound toxins. OL-HDF with new PMMA membranes could be a good dialysis strategy for adding convective transport to the well-known mechanisms of diffusion and absorption previously described with conventional PMMA membranes, enabling an adequate substitution volume.

P1393A SYSTEM FOR FORECASTING OF DRUG DOSAGE FOR BONE MINERAL DISORDERS CORRECTION IN PATIENTS ON CHRONIC DIALYSIS

Abstract Background and Aims Bone and mineral disorders (BMD) is a common complication of CKD in patients on chronic dialysis. Timely and adequate correction of BMD is the most important aspect of patient's treatment. This work presents a system for forecasting of phosphate-binding agents (PBA) dosage and vitamin D receptor activators (VDRA) dosage. The system consists of sequentially triggering artificial neural network forecasting models (separate model for each drug type). Method As an input dataset, system uses patient’s results of laboratory studies (blood calcium, phosphate and PTH) for the period of 6 months, information on previous drug therapy and data on adequacy of patient’s dialysis therapy. The output of the system are dosages of PBA an VDRA that have to be administered in order to bring the patient’s parameters as close as possible to target range of values (2.1-2.5 mmol/l for calcium, 0.87-1.5 mmol/l for phosphate and 150-300 pg/ml for PTH). The system consists of two sequentially triggering forecasting models (for PBA and for VDRA), where each model is an artificial neural network, that has been trained on a data, collected in more than 20 “Nefrosovet” hemodialysis clinics for the period of 3 years. The effect of system usage was examined for the group of 356 hemodialysis patients with median follow-up time of 3 month. The primary end-points were a number of patients in target range of values With respect to calcium (2.1-2.5 mmol/l), phosphate (0.87-1.5 mmol/l) and PTH (150-300 pg/ml). Results During the study we determined that as a result of using the dose forecasting system, number of patients in target range of values significantly increased with respect to calcium (from 178 to 209, p=.0196), phosphate (from 99 to 152, p=.0000), and PTH (from 83 to 109, p=.0281). Conclusion Employment of automated drug dosage forecasting system based on artificial neural network models, has a positive effect on BMD correction quality, which, in turn, reduces the risk of possible complications.