Serum Phosphorus Concentrations Research Articles

Evaluation of a Novel Enteral Phosphorus Therapy with Enteral Nutrition during a National Intravenous Sodium Phosphate Shortage.

The purpose of this study was to evaluate the efficacy and safety of intragastric administration of small volumes of sodium enema solution containing phosphorus as phosphorus replacement therapy in critically ill patients with traumatic injuries who required continuous enteral nutrition. Adult patients (>17 years of age) who had a serum phosphorus concentration <3 mg/dL (0.97 mmol/L) were evaluated. Patients with a serum creatinine concentration >1.4 mg/dL (124 µmol/L) were excluded. Patients were given 20 mL of saline enema solution intragastrically, containing 34 mmol of phosphorus and mixed in 240 mL water. A total of 55% and 73% of patients who received one (n = 22) or two doses (n = 11) had an improvement in the serum phosphorus concentration, respectively. The serum phosphorus concentration increased from 2.5 [2.1, 2.8] mg/dL (0.81 [0.69, 0.90] mmol/L) to 2.9 [2.2, 3.0] mg/dL (0.94 [0.71, 0.97 mmol/L) for those who received two doses (p = 0.222). Excluding two patients with a marked decline in serum phosphorus by 1.3 mg/dL (0.32 mmol/L) resulted in an increase in the serum phosphorus concentration from 2.3 [2.0, 2.8] mg/dL (0.74 [0.65, 0.90] mmol/L) to 2.9 [2.5, 3.2] mg/dL (0.94 [0.81, 1.03] mmol/L; n = 9; p = 0.012). No significant adverse effects were noted. Our data indicated that intragastric phosphate administration using a small volume of saline enema solution improved the serum phosphorus concentrations in most patients.

Correlation Between Serum 1,25(OH)2D3, Serum Phosphorus, and Parathyroid Hormone and Parathyroid Function After Central Lymph Node Dissection in Patients with Papillary Thyroid Carcinoma.

This work was to demonstrate the relationship between serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), serum phosphorus (SP), and parathyroid hormone (PTH) and parathyroid function after central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). 200 PTC patients after CLND were included, who were rolled into a control group (CG) (n = 89 cases without hypoparathyroidism) and an observation group (OG) (n = 111 cases with complicated hypoparathyroidism). The 1,25(OH)2D3, SP, and PTH levels were detected, and the diagnostic effect of these indicators was assessed. The serum PTH levels of patients in CG after surgery were normal relative to those before surgery, while the serum PTH of patients in OG was relatively lower. 1,25(OH)2D3 concentration of patients in OG was also inferior to CG, while the SP level was superior (P < 0.05). Hypoparathyroidism was positively correlated with serum PTH (r = 0.382) and 1,25(OH)2D3 (r = 0.321) and negatively correlated with SP (r = - 0.211). The area under the curve (AUC) (0.893), sensitivity (90.83%), and specificity (94.77%) of the joint diagnosis of 1,25(OH)2D3 + SP + PTH were greatly superior to those of the single diagnosis and the pairwise diagnosis with the three indicators (P < 0.05). Hypoparathyroidism in patients with PTC after CLND surgery was positively correlated with 1,25(OH)2D3 and PTH and negatively correlated with SP concentration. In addition, the combination diagnosis of 1,25(OH)2D3, PTH, and SP worked well.

Serum phosphorus concentration and its association with the degree and pattern of intracranial arterial calcification

Background and aimThe aim of this study was to determine whether the serum phosphorus concentrations (SPC) are associated with the degree and pattern of intracranial arterial calcification (IAC) in patients with normal renal function or mild-moderate renal impairment. Methods and resultsA total of 513 patients were enrolled in this study. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Study participants were classified according to IAC degrees (mild, moderate and severe) and patterns (intimal and medial calcification). A multivariate regression model was used to assess the independent relationship of SPC with IAC scores and patterns. Of 513 study participants (mean [SD] age, 68.3 [10.3] years; 246 females [48%]), the mean SPC was 1.07 ± 0.17 mmol/L and IAC scores was 4.0 (3.0–5.0). Multivariate analysis showed that higher serum phosphorus was a significant risk factor for moderate/severe IAC in both patients with eGFR ≥60 ml/min/1.73 m2 (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01–1.59; P < 0.05) and eGFR <60 ml/min/1.73 m2 (OR, 1.92; 95% CI, 1.04–3.57; P < 0.05), when those with mild IAC were considered as the reference group. However, higher SPC was associated with an increased odds of medial calcification only in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.67; 95% CI, 1.08 to 2.61). ConclusionsHigh levels of serum phosphorus were positively correlated with the degree of IAC, and this significant effect on medial IAC was only present in patients with impaired renal function (eGFR <60 ml/min/1.73 m2).

Effect of Egg-White Protein Alone or Combined With Niacin on Nutritional Status, and Phosphorus Control in Maintenance Hemodialysis Patients: A Randomized Controlled Trial

BackgroundNiacin is reported to decrease phosphorus concentration in Maintenance Hemodialysis (MHD) patients. Egg white is one of the main substitutable proteins in MHD patients due to its low phosphorus content. Therefore, we aimed to evaluate the effects of combined egg white and niacin supplementation on dialysis patients' serum phosphorus and nutritional biomarkers. MethodsIn this randomized controlled clinical trial, 98 patients on MHD were randomly allocated to four groups for eight weeks: 24 g egg white (n=25), 600 g niacin daily (n=24), egg white combined with niacin (n=24), and control (n=24). Calcium, phosphorus, fibroblast growth factor-23, and other nutritional markers were assessed. ResultsThere was a significant difference among the groups only in phosphorus at the end of the trial, which was significantly lower in the niacin group (4.38+0.812 mg/dl) than in both the egg white (5.07+0.49 mg/dl) and egg white with niacin supplementation (5.41+0.662 mg/dl) groups. In this regard, albumin increased in egg white and egg white with niacin supplementation, while albumin did not change significantly in the niacin group. Urea reduction ratio and Kt/V rose only in the egg-white group, while aspartate aminotransferase increased only in the niacin and control groups. ConclusionNiacin decreases serum phosphorus concentration more than egg-white protein or a combined intervention. Egg white protein supplementation has beneficial effects on some nutritional statuses other than phosphorus control without the side effects of niacin.

Serum Phosphorus Management with Sucroferric Oxyhydroxide as a First-Line Phosphate Binder within the First Year of Hemodialysis.

Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis. We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year. The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p &lt; 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p &lt; 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p &lt; 0.0001 vs. baseline). Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.

Phosphorus balance calculator: an individualized tool for treatment of hyperphosphatemia in hemodialysis patients.

Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are the common obstacle to assess phosphorus balance and control phosphorus in hemodialysis patients. We aimed to investigate whether the individualized therapy using phosphorus balance calculator improves phosphorus control. A randomized, open-label, multicenter, 4-week clinical trial was conducted. 119 maintenance hemodialysis patients aged 18 to 85 years old and with serum phosphorus level higher than 1.45mmol/l from 3 university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n=60), or conventional therapy (n=59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment. Among 119 randomized participants (mean age, 62 years; 68 male[57%]), 116 completed the trial. By using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state, significantly reduced the serum phosphorus (1.62±0.45mmol/l versus 1.85±0.45 mmol/l, P=0.006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P=0.006), and had greater adjusted mean difference in change in serum phosphorus over the 4 weeks (-0.47 versus -0.23mmol/l, P=0.010) when compared to conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, and adjusted mean difference of serum calcium and PTH levels over the treatment period. Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia.

The significance of short-term preoperative calcium and activated vitamin D3 supplementation in thyroidectomy: a randomized trial and prospective study.

The aim was to explore the effects of preoperative calcium and activated vitamin D3 supplementation on post-thyroidectomy hypocalcemia and hypo-parathyroid hormone-emia (hypo-PTHemia). A total of 209 patients were randomly divided into control group (CG) and experimental group (EG). Oral calcium and activated vitamin D3 supplementation were preoperatively administered to EG, whereas a placebo was administered to CG. Data on serum calcium, phosphorus, and PTH concentrations before operation, on postoperative day 1 (POPD1), at postoperative week 3 (POPW3), and on the length of postoperative hospitalization were collected. The serum calcium, phosphorus, and PTH concentrations, as well as the incidence of postoperative hypocalcemia and hypo-PTHemia, did not significantly differ between EG and CG. Subgroup analysis revealed that the serum calcium concentrations of the experimental bilateral thyroidectomy subgroup (eBTS) on POPD1 and POPW3 were higher than that of the control bilateral thyroidectomy subgroup (cBTS) (P < 0.05); the reduction of serum calcium in eBTS on POPD1 and POPW3 was less than those in cBTS (P < 0.05). However, significant differences were not observed between the unilateral thyroidectomy subgroups (UTS) (P > 0.05). Moreover, the incidence of postoperative hypocalcemia in cBTS on POPD1 was significantly higher than that in eBTS (65.9% vs 41.7%) (P < 0.05). The length of hospitalization in cBTS (3.55 ± 1.89 days) was significantly longer than that (2.79 ± 1.15 days) in eBTS (P < 0.05). Short-term preoperative prophylactic oral calcium and activated vitamin D3 supplementation could effectively reduce the incidence of postoperative hypocalcemia and decrease the length of postoperative hospitalization in patients who have undergone bilateral thyroidectomy.

Predictors of Developmental Defects of Enamel in Primary Maxillary Central Incisors Using Bayesian Model Selection

Introduction: Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP), and post-eruptive breakdown (PEB) using the enamel defects index. To better understand the etiology of DDE, we assessed the linkages amongst exposome variables for these defects during the specific time duration for enamel mineralization of the human primary maxillary central incisor enamel crowns. In general, these two teeth develop between 13 and 14 weeks in utero and 3–4 weeks’ postpartum of a full-term delivery, followed by tooth eruption at about 1 year of age. Methods: We utilized existing datasets for mother-child dyads that encompassed 12 weeks’ gestation through birth and early infancy, and child DDE outcomes from digital images of the erupted primary maxillary central incisor teeth. We applied a Bayesian modeling paradigm to assess the important predictors of EH, OP, and PEB. Results: The results of Gibbs variable selection showed a key set of predictors: mother’s prepregnancy body mass index (BMI); maternal serum concentrations of calcium and phosphorus at gestational week 28; child’s gestational age; and both mother’s and child’s functional vitamin D deficiency (FVDD). In this sample of healthy mothers and children, significant predictors for OP included the child having a gestational period >36 weeks and FVDD at birth, and for PEB included a mother’s prepregnancy BMI <21.5 and higher serum phosphorus concentration at week 28. Conclusion: In conclusion, our methodology and results provide a roadmap for assessing timely biomarker measures of exposures during specific tooth development to better understand the etiology of DDE for future prevention.

B-005 Blood pH and Phosphate Tend to Follow an Inversely Correlated Homeostatic Status

Abstract Background Phosphorus containing biomolecules perform an essential biochemical function in maintaining extra and intracellular acid-base status. Maintaining normal concentration (2.5–4.5 mg/dl) of phosphorus is indispensable for optimal cellular function and homeostasis. Serum concentration of phosphorus (mainly inorganic orthophosphates) is an indicator of H2PO4−/HPO42− acid-base buffer condition. Disturbance of pH could be an immediate impact of many respiratory and metabolic morbidities. Extra/intracellular redistribution of phosphates in response to an abnormal pH is an established homeostatic phenomenon. Failure to maintain an appropriate phosphate level to support the extra/intracellular redistribution may result in a pH shock. Therefore, it is important to have a clear understanding on how blood phosphate and pH levels are interconnected which could assist in guiding therapeutic interventions to fix phosphate abnormalities and acid-base disturbances. This study examined the homeostatic correlation between blood pH and phosphate level among hospitalized and ambulatory patients. Methods Serum phosphorus concentration and pH were retrieved from the biochemical profiles and arterial blood gas data of hospitalized and ambulatory patients who presented or admitted our tertiary care level university hospital during the first week of July, 2021. Logarithmic (base ten) values of phosphorus concentration were determined to normalize the distribution of the phosphorus data more uniform. Correlation analyses between phosphorus/log[phosphorus] and pH were performed by GraphPad PRISM version 8. Results A total of 101 corresponding blood gases and phosphate levels were obtained. Both phosphorus and log [phosphorus] values of the patients displayed an inverse correlation with arterial pH (Figure 1a and b). Pearson r values demonstrated a negative correlation between phosphorus/log [phosphorus] and pH (−0.6737 and −0.6450, respectively).Fig. 1. Conclusion Monitoring of phosphate levels provide an early indication of acid base status. Phosphorus level maintains an inverse correlation with pH profile. Therefore, a therapeutic manipulation of phosphorus or pH may have a mutual effect requiring further investigation.

A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype.

X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype-phenotype correlation in a cohort of XLH patients. This is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study. A total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%. Our analysis did not identify any specific genotype as a predictor. No significant genotype-phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment.

Clinical significance of adanced glycation end products and inflammation products in the development of vascular calcification and cardiovascular complications in chronic kidney disease

Background. Vascular calcification underlies cardiovascular complications, which remain the leading cause of high mortality in chronic kidney disease (CKD). Uremic toxins, including the advanced glycation end products, play a significant role in the formation of this process.The Aim of the study is to clarify the role of the advanced glycation end products (AGEs) and inflammationproducts in the processes of vascular calcification at different stages of CKD.Patients and Methods. 105 patients aged 18 to 66 years at different stages of CKD C1-C5D were examined, 75 of which were caused by diabetic nephropathy (DN), 30 by other nosological forms. Serum concentrations of AGEs, IL6, TNF-α, troponin I, parathyroid hormone (PTH) were determined by enzyme immunoassay (ELISA). To study the AGEs concentration, the serum was separated by centrifugation (in Eppendorf tubes). The samples were stored at – 70 °C. The left ventricular myocardial mass index (LVMI) was determined. Left ventricular hypertrophy (LVH) was diagnosed with LVH&gt;115 g/m2 for men and &gt;95 g/m2 for women. The peak systolic velocity of blood flow in the aortic arch (Vps) was studied by duplex scanning using the Doppler effect.Results. A significant increase in serum phosphorus concentration (p &lt; 0.05) and PTH (p&lt; 0.01) was revealed as the glomerular filtration rate decreased. An increase in the concentration of AGEs, IL6 and TNF-α was found at all stages of CKD, most pronounced at the later stages – C4-C5D ((p&lt; 0.01, p&lt; 0.05, p&lt;0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α. CONCLUSION. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD. Keywords: advanced glycation end products, inflammation, vascular calcification, chronic kidney disease&gt;˂0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α.Conclusion. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD.

Effects of Different Proportions of Amaranthus hypochondriacus Stem and Leaf Powder Inclusions on Growth Performance, Carcass Traits, and Blood Biochemical Parameters of Broilers.

This experiment aimed to study the effects of different proportions of Amaranthus hypochondriacus stem and leaf powder (AHSL) on the growth performance, apparent nutrient digestibility, carcass traits, meat quality, and blood biochemical parameters of broilers from day 1 to day 42. The experiment utilized a single-factor experimental design, with a total of 216 one-day-old male broilers (Ross 308) randomly assigned to three dietary treatment groups (eight replicate cages of nine birds per cage). The dietary treatments included a control diet, a 3% AHSL diet and a 6% AHSL diet for days 0-21. Then, the 3% and 6% AHSL diets were changed to 5% and 10% AHSL for days 22-42. The results showed that the inclusion levels of AHSL did not affect growth performance, carcass traits, or meat quality on days 21 and 42 (p > 0.05). However, the inclusion levels of AHSL decreased the apparent nutrient digestibility (AND) of dry matter (DM) (p ˂ 0.001) and neutral detergent fiber (NDF) (p ˂ 0.001) and increased the serum concentration of phosphorus (p ˂ 0.001) on day 21. On day 42, the inclusion levels of AHSL decreased the AND of DM (p = 0.025) and NDF content (p ˂ 0.001), but increased the AND of crude protein (CP) (p = 0.004). In particular, the diet containing 10% AHSL significantly increased the serum enzyme activity of alkaline phosphatase (ALP) (p = 0.046) and the serum concentration of total protein (TP) (p ˂ 0.001) on day 42. Overall, AHSL can be used as a new and effective feed ingredient in broiler diets. It can replace part of the corn-soybean meal diet without any adverse effects, which is beneficial for conserving feed resources. Additionally, AHSL can be included at a level of up to 10% during the broiler growth period.

Powder and agglomerated free-choice minerals for grazing cattle: animal responses and chemical and physical alterations of the mineral mixture

ABSTRACTThe aim was to evaluate the animal response and the chemical and physical changes of free-choice mineral mixtures fed to grazing cattle. Growing beef cattle were fed either powder (POW) or agglomerated (AGL) mineral mixtures in three different experiments (Exp.), carried out in pastures of Brachiaria grass. In Exp. 1 and 2, the mineral mixtures were disposed in unsheltered troughs (POWun vs. AGLun), being delivered once (D0, Exp.1) or twice (D0 and D8, Exp. 2), throughout 14-day periods. In Exp. 3, POWun and AGLun were additionally compared to POW in sheltered troughs (POWshe), and the mineral mixtures were disposed in D0, throughout 21-day periods. Non-consumed supplement was removed and sampled on D14 (Exp. 1 and 2) or D21 (Exp. 3). Evaluations included average daily body weight gain (ADG), daily disappearance of the supplement (DSD), penetration force of the supplement mass, faecal chemical composition and serum levels of Ca, P and Mg. In Exp. 1, no effects were observed on ADG and faecal mineral concentrations, however, changes in mineral concentrations and a 40% reduction in Na concentration in the supplement were observed, compared to the initial concentration. AGLun had a lower penetration force. In Exp. 2, there were no effects on DSD and faecal mineral concentrations. POWun showed a smaller reduction in Na content compared to AGLun, and AGLun showed lower penetration force. In Exp. 3, the treatments did not affect ADG, but there was a trend towards higher DSD and serum phosphorus (P) concentration for AGLun (p = 0.08). Higher faecal Na concentration was observed for AGLun and higher Na concentration occurred in non-consumed mixture of POWshe. Mineral supplements offered in uncovered troughs showed altered chemical and physical characteristics, with possible effects on supplement intake. However, the general changes are unlikely to alter animal performance.

Enhanced intestinal microflora composition and phosphorus-transportation efficiency in fast-growing spotted seabass (Lateolabrax maculatus) fed a low-phosphorus diet

This study examined differences in the intestinal microflora composition and phosphorus-transportation efficiency between fast- and slow-growing spotted seabass (Lateolabrax maculatus) fed a low-phosphorus diet. A total of 60 spotted seabass (9.48 ± 0.19 g) were randomly distributed into three tanks at a density of 20 fish per tank and fed a low-phosphorus diet for eight weeks. At the end of the experiment, the four heaviest and four lightest individuals from each tank were sampled as the fast-growing spotted seabass (FGS) and slow-growing spotted seabass (SGS), respectively. FGS had significantly higher weight gain (WG) than those in SGS. Higher whole-body phosphorus deposition, serum phosphorus content and the mRNA expression of genes associated with phosphorus transportation (NaPIiib, PiT1, and PiT2) were observed in FGS compared to SGS. Moreover, lower serum alkaline phosphatase (AKP) activity was found in FGS compared to SGS. However, no significant differences were found in liver phosphorus deposition or serum parathyroid hormone (PTH) levels between FGS and SGS. Compared to SGS, higher relative abundances of operational taxonomic units (OTUs) and potential probiotics, including Lactobacillus and Cetobacterium, and lower relative abundances of potentially pathogenic bacteria, including Enhydrobacter and Chryseobacterium, were observed in the intestinal microflora of FGS. Overall, these findings suggested that higher growth rates in spotted seabass fed a low-phosphorus diet were associated with enhanced phosphorus-transportation efficiency and intestinal microflora composition.

Fam83h mutation causes mandible underdevelopment via CK1α-mediated Wnt/β-catenin signaling in male C57/BL6J mice.

Truncation mutations in FAM83H are the major cause of autosomal dominant hypocalcified amelogenesis imperfecta. Some studies also indicated that FAM83H could be involved in osteogenic differentiation; however, the function of FAM83H in bone formation was rarely explored. This study aimed to explore the effect of Fam83h mutation on skeletal development. We generated Fam83h c.1186C>T (p.Q396*) knockin C57/BL6J mice by CRISPR/Cas9 technology and found that the Fam83hQ396⁎/Q396⁎ male mice presented skeletal development retardation that was inconspicuous at birth but progressively worsened as they grew up. Alcian and Alizarin Red staining of the whole-mount skeleton showed Fam83hQ396⁎/Q396⁎ mice presented obvious skeletal development retardation. Moreover, Micro-computed tomography (Micro-CT) analysis and H&E staining showed that the mandible of Fam83hQ396⁎/Q396⁎ mice exhibited decreased bone trabecula and slight bone rarefaction compared with wild-type mice. Calcium and phosphorus content of serum and bone, and serum ALP activity analysis showed that the serum ALP activity and value of bone calcium were decreased in Fam83hQ396⁎/Q396⁎ mice. The reduced expression of mineralization markers of RUNX2, OSX, OCN, and COL1, the reduced ALP activity and the weakened ARS staining exhibited in osteoblasts isolated from 3-day-old Fam83hQ396⁎/Q396⁎ mice. The increased protein expression of casein kinase 1α (CK1α) in the cytoplasm and the decreased expression of β-CATENIN in the nucleus indicated the inhibiting Wnt/β-catenin signaling in osteoblasts from Fam83hQ396⁎/Q396⁎ mice. Furthermore, agonists of Wnt/β-catenin signaling and Ck1α siRNA partially reversed the mineralization inhibition and the decreased expression of key signaling molecules in osteoblasts of Fam83hQ396⁎/Q396⁎ mice. In conclusion, Fam83h mutation caused the increase of cytoplasmic CK1α (as one of the components of the degradation complex), which in turn promoted degradation of β-CATENIN in the cytoplasm and reduced β-CATENIN translocation into the nucleus, subsequently inhibited Wnt/β-catenin signaling in osteoblast differentiation, and thus resulted in the mandible underdevelopment in Fam83hQ396⁎/Q396⁎ male mice.

#3775 PHOSPHATE BINDERS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE UNDERGOING DIALYSIS: A NETWORK META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS

Abstract Background and Aims Phosphate binders (PBs) are essential for proper serum phosphorus control in patients with chronic kidney disease (CKD) requiring dialysis along with adequate dialysis and phosphorus restriction. To evaluate the clinical efficacy and safety of each PBs, we conducted a systematic review (SR) using a network meta-analysis (NMA) of randomised controlled trials (RCTs). Method We searched published RCTs in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials (CENTRAL), and Clinical trial.gov databases using the search terms and text words relevant to this SR. We included RCTs involving adults (18 years and older) with at least 8 weeks of follow-up. Interventions and controls were the following: sevelamer-, bixalomer-, tenapanor-, iron- (ferric citrate, sucroferric oxyhydroxide), calcium-, magnesium-, lanthanum-, aluminium-, nicotinic acid-, and standard treatment or placebo). The outcomes were all-cause mortality, gastrointestinal adverse events (AEs), coronary artery calcium score (CACS), and serum calcium, phosphorus, and bicarbonate concentrations. Summary estimates were expressed as relative risk (RR) for binary outcomes and mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, respectively, with 95% confidence intervals (CI). The protocol of this study is registered in PROSPERO: CRD42022328388. Results All-cause mortality was identified and analysed in 29 trials involving 12,622 participants. Compared with calcium-containing PBs, sevelamer reduced the risk of all-cause mortality (RR 0.65, 95%CI 0.45 to 0.96). The risk of gastrointestinal AEs was higher for nicotinic acid (RR 3.79, 95%CI 1.29 to 11.12), sucroferric oxyhydroxide (RR 1.96, 95%CI 1.47 to 2.63), sevelamer (RR 1.47, 95%CI 1.14 to 1.88), and lanthanum (RR 1.36, 95%CI 1.14 to 1.64) than calcium-containing PBs. Lanthanum had an inhibitory effect on CACS progression compared to calcium-containing PBs (SMD -0.63, 95% CI -1.05 to -0.22). Serum calcium was lower than calcium-containing PBs in the following order: magnesium (MD -0.67, 95% CI -1.12 to -0.22), placebo (MD -0.64, 95% CI -1.22 to -0.67), nicotinic acid (MD -0.56, 95% CI -1.11 to -0.005), sevelamer (MD -0.35, 95% CI -0.47 to -0.23), and lanthanum (MD -0.24, 95% CI -0.38 to -0.095). No significant difference was observed in serum phosphorus decrease between any PBs and calcium-containing PBs. Serum bicarbonate concentration increased with ferric citrate (MD 1.16, 95% CI 0.36 to 1.96) and sucroferric oxyhydroxide (MD 1.06, 95% CI 0.29 to 1.82) but decreased with sevelamer (MD -1.24, 95% CI -1.71 to -0.77). Conclusion Our findings from SR based on NMA suggest that lanthanum may attenuate CACS and sevelamer may reduce the risk of all-cause mortality compared to calcium-containing PBs in patients with CKD requiring dialysis.

#6606 MEDICATION VOLUME COMPARISON TO BIND PHOSPHATE

Abstract Background and Aims Elevated phosphate concentrations are associated with a significantly increased risk of cardiovascular disease and overall mortality in patients with chronic kidney disease. Current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend lowering elevated serum phosphorus concentrations toward the normal range in patients with end-stage kidney disease on dialysis through restriction of dietary phosphorus intake, increase in clearance by dialysis, and the use of phosphate binders. However, ∼75% of dialysis patients are not achieving normal phosphate concentrations, potentially due to low adherence and/or binders’ insufficient phosphate binding capacity to match dietary intake. A phosphate binder with a higher phosphate binding capacity could improve phosphate control and potentially clinical outcomes. This study evaluated the medication volume of various phosphate binders to bind 1 gram of phosphorus. Methods Five phosphate binders were assessed: ferric citrate (210 mg ferric iron), calcium acetate (667 mg calcium acetate), lanthanum carbonate (500 and 1,000 mg lanthanum), sevelamer carbonate (800 mg sevelamer carbonate), and lanthanum dioxycarbonate (500 and 1,000 mg lanthanum). The mean daily dose volume to bind 1 g of phosphate was calculated as volume per tablet multiplied by the mean number of tablets taken per day. The volume to bind 1 g of phosphate was calculated by dividing the volume per tablet by its in vivo binding capacity, based on NIH DailyMed website. Results Binding to 1 g of phosphate required 5.6 cm3 of lanthanum dioxycarbonate compared with lanthanum carbonate (19.8 cm3), calcium acetate binders (25.0 cm3), ferric citrate (46.5 cm3), and sevelamer carbonate (73.4 cm3) (Figure 1). Conclusion The study found that lanthanum dioxycarbonate had the lowest volume to bind the same amount of phosphate compared to other binders. With a low medication volume and high phosphate binding capacity, lanthanum dioxycarbonate, a novel investigational nanotechnology product, can be a welcoming choice for patients to manage their hyperphosphatemia. The drug's decreased pill size (making it easy to swallow) and its tolerability have the potential to increase medication adherence and improve phosphate control.

Cross-sectional characterization of renal function in cats with caudal stomatitis.

The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats. A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a t-test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test. Relative to the control group, cats in the CS group had significantly lower serum creatinine (P <0.001) and albumin concentrations (P <0.001), urine specific gravity (P = 0.024) and hematocrit (P = 0.003), and higher serum phosphorus (P <0.001), potassium (P <0.001) and globulin concentrations (P <0.001), white blood cell count (P <0.001) and urine protein:creatinine ratio (P = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups. The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.

Effects of Donepezil on the Musculoskeletal System in Female Rats.

The extension of human life makes it more and more important to prevent and treat diseases of the elderly, including Alzheimer's disease (AD) and osteoporosis. Little is known about the effects of drugs used in the treatment of AD on the musculoskeletal system. The aim of the present study was to investigate the effects of donepezil, an acetylcholinesterase inhibitor, on the musculoskeletal system in rats with normal and reduced estrogen levels. The study was carried out on four groups of mature female rats: non-ovariectomized (NOVX) control rats, NOVX rats treated with donepezil, ovariectomized (OVX) control rats and OVX rats treated with donepezil. Donepezil (1 mg/kg p.o.) was administered for four weeks, starting one week after the ovariectomy. The serum concentrations of CTX-I, osteocalcin and other biochemical parameters, bone mass, density, mineralization, histomorphometric parameters and mechanical properties, and skeletal muscle mass and strength were examined. Estrogen deficiency increased bone resorption and formation and worsened cancellous bone mechanical properties and histomorphometric parameters. In NOVX rats, donepezil decreased bone volume to tissue volume ratio in the distal femoral metaphysis, increased the serum phosphorus concentration and tended to decrease skeletal muscle strength. No significant bone effects of donepezil were observed in OVX rats. The results of the present study indicate slightly unfavorable effects of donepezil on the musculoskeletal system in rats with normal estrogen levels.

Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study

Background/ObjectivesThiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. Subjects/MethodsThis observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. ResultsA total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). ConclusionsOur results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.