Serum Phosphate Concentrations Research Articles

Effect of 2 dosages of prepartum cholecalciferol injection on blood minerals, vitamin D metabolites, and milk production in multiparous dairy cows: A randomized clinical trial

The objective of the present study was to evaluate the effect of 2 dosages of prepartum cholecalciferol injection on blood minerals, vitamin D metabolites, and milk production. Cows entering their second or greater lactation (n = 158) were randomly assigned to a control group (CON) or one of 2 treatment groups receiving either 6 × 106 IU (6VitD) or 12 × 106 IU (12VitD) cholecalciferol intramuscularly on d 275 ± 1.2 (SD) of gestation. Concentrations of serum total Ca (tCa), phosphate, and Mg were determined on 1, 2, 3, 5, 7, and 10 d in milk (DIM). For a subsample of 30 cows entering the third lactation (n = 10/group), these samples were analyzed for cholecalciferol, 25-hydroxycholecalciferol (25-OHD3), and 24,25-dihydroxycholecalciferol (24,25-[OH]2D3). In these cows, we also determined 1,25-dihydroxycholecalciferol (1,25-[OH]2D3), the biologically most active metabolite, on 1, 2, 3, and 5 DIM. Repeated measures ANOVA was performed to evaluate the effect of different dosages of cholecalciferol on blood minerals, vitamin D metabolites, and milk yield over the first 5 test days after calving. Binary outcomes such as retained placenta and metritis were analyzed using a chi-squared test. Although the 12VitD treatment increased tCa concentrations on 1, 2, and 3 DIM compared with CON, administration of 6VitD increased tCa concentrations only on 1 DIM. Compared with CON cows and 6VitD cows, 12VitD cows had greater serum phosphate concentration during the first 10 DIM. Furthermore, 6VitD cows had greater serum phosphate concentrations compared with CON cows. On the contrary, 12VitD cows had lower serum Mg concentrations during the first 10 DIM compared with CON and 6VitD cows. Cholecalciferol was increased by the treatment and decreased quickly until 10 DIM. In respect to 25-OHD3, the 6VitD treatment resulted in a 4.1-fold increase in comparison to the CON group, while a 6.5-fold increase was observed in 12VitD animals. The vitamin D metabolite 24,25-(OH)2D3 increased linearly with 25-OHD3 serum levels, resulting in the highest concentrations in the 12VitD group. An increase of 1,25-(OH)2D3 until 3 DIM was observed in all cows. However, this rise was most pronounced in the CON group. The incidence of retained placenta was 1.9%, 11.5%, and 29.6%, and that of metritis was 11.5%, 15.4%, and 31.5% for CON, 6VitD, and 12VitD cows, respectively. Although none of the treated cows exerted clinical signs of hypocalcemia, one cow in CON incurred clinical hypocalcemia. Cows of the 12VitD group had a lower milk yield over the first 5 monthly test days compared with the control and 6VitD group (42.2 ± 0.5, 42.0, ± 0.5 and 40.7 ± 0.5 kg for control cows, 6VitD cows and 12VitD cows, respectively). Although no negative side effects were observed in 6VitD cows, we do not recommend the general application of 6 × 106 IU cholecalciferol before calving as positive effects on calcium homeostasis were marginal and restricted to the first DIM. The present findings confirm that the application of 12 × 106 IU cholecalciferol negatively affected milk production on this farm.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model

Introduction: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. Methods: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. Results: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. Conclusions: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Population pharmacokinetic and exposure-response analyses of pemigatinib in patients with advanced solid tumors including cholangiocarcinoma.

Pemigatinib is a selective, potent, oral inhibitor of fibroblast growth factor receptor (FGFR)1-3 with efficacy in patients with previously treated, advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 alterations. A previously developed population pharmacokinetic (PK) model of pemigatinib was refined using an updated dataset with 467 participants from seven clinical studies, including patients with CCA. Updated PK model parameters were used to evaluate the association between pemigatinib exposure and efficacy and safety. Pemigatinib PK was adequately described by a two-compartment model with linear elimination and sequential zero- and first-order absorption. The final model successfully minimized, had a successful covariance step, and showed unbiased goodness-of-fit. Estimated first-order absorption rate constant and apparent clearance were 3.7/h and 10.7 L/h, respectively. Sex, baseline body weight, and concomitant use of phosphate binders, proton pump inhibitors, or histamine-2 antagonists significantly impacted PK parameters; however, the impact of covariates on PK exposure was not clinically significant. Steady-state pemigatinib exposure and mean change from baseline in serum phosphate concentration were associated with objective response rate in a bell-shaped relationship and were significantly associated with increased hyperphosphatemia. Pemigatinib exposure was associated with treatment-emergent adverse events, such as decreased appetite, nausea, and stomatitis, although the relationships were shallow. Overall, analyses indicate that 13.5 mg pemigatinib once daily in 21-day cycles (2 weeks on, 1 week off) offers a favorable benefit-risk profile in patients with advanced/metastatic or surgically unresectable CCA and is the optimal dose for clinical development.

The SGLT2 inhibitor dapagliflozin improves kidney function in glycogen storage disease XI.

Glycogen storage disease XI, also known as Fanconi-Bickel syndrome (FBS), is a rare autosomal recessive disorder caused by mutations in the SLC2A2 gene that encodes the glucose-facilitated transporter type 2 (GLUT2). Patients develop a life-threatening renal proximal tubule dysfunction for which no treatment is available apart from electrolyte replacement. To investigate the renal pathogenesis of FBS, SLC2A2 expression was ablated in mouse kidney and HK-2 proximal tubule cells. GLUT2Pax8Cre+ mice developed time-dependent glycogen accumulation in proximal tubule cells and recapitulated the renal Fanconi phenotype seen in patients. In vitro suppression of GLUT2 impaired lysosomal autophagy as shown by transcriptomic and biochemical analysis. However, this effect was reversed by exposure to a low glucose concentration, suggesting that GLUT2 facilitates the homeostasis of key cellular pathways in proximal tubule cells by preventing glucose toxicity. To investigate whether targeting proximal tubule glucose influx can limit glycogen accumulation and correct symptoms in vivo, we treated mice with the selective SGLT2 inhibitor dapagliflozin. Dapagliflozin reduced glycogen accumulation and improved metabolic acidosis and phosphaturia in the animals by normalizing the expression of Napi2a and NHE3 transporters. In addition, in a patient with FBS, dapagliflozin was safe, improved serum potassium and phosphate concentrations, and reduced glycogen content in urinary shed cells. Overall, this study provides proof of concept for dapagliflozin as a potentially suitable therapy for FBS.

Mendelian randomisation and colocalization analyses reveal novel drug targets for the prevention of kidney stone disease by modulating serum calcium and phosphate concentrations

Mendelian randomisation and colocalization analyses reveal novel drug targets for the prevention of kidney stone disease by modulating serum calcium and phosphate concentrations

Tenapanor Improves Long-Term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study.

Most patients with end-stage kidney disease and hyperphosphatemia have difficulty controlling serum phosphate concentrations (sP) despite maintenance dialysis, dietary restriction, and phosphate binder treatment. NORMALIZE evaluated the efficacy and safety of tenapanor 30 mg twice daily alone or in combination with phosphate binders to achieve sP within the adult population reference range (2.5-4.5 mg/dL). Patients who completed the phase 3 PHREEDOM study could enroll in NORMALIZE. Patients enrolled in NORMALIZE who had received tenapanor during the PHREEDOM study (n=111) added sevelamer carbonate if sP was >4.5 mg/dL. Patients who had received sevelamer carbonate during the PHREEDOM study (n=61) added tenapanor and decreased sevelamer carbonate if sP was ≤4.5 mg/dL, per protocol titration schedule. Patients were followed in NORMALIZE for up to 18 months. We assessed efficacy in the full analysis set (FAS), defined as patients who received ≥1 dose of study drug and had ≥1 posttreatment sP measurement (n=171). We assessed safety in all patients who received ≥1 dose of study drug (n=172). At the endpoint visit, 57 of 171 patients (33%) in the FAS achieved sP between 2.5 and 4.5 mg/dL. Eight of 23 patients (35%) who were on tenapanor alone at the endpoint visit achieved sP between 2.5 and 4.5 mg/dL. The mean reduction from PHREEDOM baseline to end of NORMALIZE in sP was 2.0 mg/dL. Serum iFGF23 was significantly reduced; serum iPTH was significantly reduced among patients with iPTH ≥300 pg/mL at PHREEDOM baseline. The most commonly reported treatment-emergent adverse event was diarrhea in 38 of 172 patients (22%), which led to tenapanor discontinuation in 4 patients (2%). Tenapanor alone or in combination with phosphate binders helped adult patients on maintenance dialysis achieve normal sP concentrations. Safety was consistent with previous studies of tenapanor. A Long-Term Study to Evaluate the Ability of Tenapanor Alone or in Combination With Sevelamer to Treat to Goal Serum Phosphorus in Patients With End-Stage Kidney Disease on Dialysis (NORMALIZE), NCT03988920.

Constipation and clinical outcomes in peritoneal dialysis: Results from Thailand PDOPPS.

Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes. We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis. Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin. Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.

Cystic Parathyroid Adenomas as a Risk Factor for Severe Hypercalcemia.

(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.

Hypophosphataemia definitions, incidence and associated outcomes in paediatric intensive care: A retrospective cohort study in post-cardiac surgical patients

Hypophosphataemia has been linked to higher morbidity and mortality in intensive care but there is inconsistency in the definition of hypophosphataemia for infants and children. We aimed to determine the incidence of hypophosphataemia in a group of at-risk children in paediatric intensive care unit (PICU) and associations with patient characteristics and clinical outcomes using three different hypophosphataemia thresholds. Retrospective cohort study of 205 post-cardiac surgical patients <2 years of age admitted to Starship Child Health PICU, Auckland, New Zealand. Patient demographics and routine daily biochemistry for 14 days after PICU admission were collected. Rates of sepsis, mortality and length of mechanical ventilation were compared between groups with different serum phosphate concentrations. Out of 205 children, 6 (3%), 50 (24%) and 159 (78%) had hypophosphataemia at thresholds of <0.7, <1.0 and <1.4 mmol/L, respectively. There were no differences in gestational age at birth, sex, ethnicity or mortality in those with and without hypophosphataemia at any threshold. Children with a serum phosphate <1.4 mmol/L had more mean (SD) total hours of mechanical ventilation (85.2 (79.6) vs. 54.9 (36.2) h, P = 0.02) and those with mean serum phosphate <1.0 mmol/L had more mean hours of mechanical ventilation (119.4 (102.8) vs. 65.2 (54.8) h, P < 0.0001), episodes of sepsis (14% vs. 5%, P = 0.03) and longer length of stay (6.4 (4.8-20.7) vs. 4.9 (3.9-6.8) days, P = 0.02). Hypophosphataemia is common in this PICU cohort and serum phosphate <1.0 mmol/L is associated with increased morbidity and length of stay.

#2918 SERUM 25(OH)-VITAMIN D AND 1,25(OH)2 VITAMIN D IN HEMODIALYSIS PATIENTS: FACTORS AFFECTING THEIR CONCENTRATIONS AND THEIR EFFECT ON SURVIVAL

Abstract Background and Aims In haemodialysis patients, serum levels of vitamin D metabolites, 25-hydroxy-vitamin D (25D), a nutritional status of vitamin D, and 1,25-dihydroxy-vitamin D (1,25D), an active form of vitamin D, are previously reported to be low. In recent years of new CKD-MBD guidelines utilizing calcimimetics, vitamin D receptor agonists (VDRA) and new phosphate binders, relationship between serum 25D, 1,25D concentrations and clinical parameters in haemodialysis patients are not well known. We measured both serum 25D and 1,25D concentrations in chronic haemodialysis patients, and examined their association with several clinical factors and also with survival, in both cross-sectional and longitudinal analyses. Method A total of 108 stable haemodialysis patients (72 ± 10 year-old, 64 males, haemodialysis duration 6.9 ± 7.5 years, 45 with type 2 diabetes) were examined. Serum 25D was measured by a ECRIA method, and 1,25D by a RIA2 antibody method, and serum PTH by a IRMA assay. In a cross-sectional analysis, association of these vitamin D metabolites with clinical parameters was examined. In a longitudinal study, patients were followed for 3 years and survival of the patients was examined in relation with these vitamin D metabolites. Results Serum 25D concentrations were 12.0 ± 4.0 ng/ml, being hypovitaminosis D (&amp;lt;30 ng/ml) in all patients. Serum 1,25D concentrations were 14.7 ± 8.7 pg/ml, being lower than normal ranges (60-120 pg/ml) in 93% of the patients. There was no significant differences in 25D or 1,25D between those with diabetes and without. Although there was no significant correlation between 25D and haemodialysis duration, there was a significant negative correlation between 1,25D and haemodialysis duration (r = -0.187, p = 0.042). Neither of 1,25D or 25D was significantly correlated with serum calcium or phosphate concentrations. There was a significant, positive correlation between 25D and serum albumin (r = 0.172, p = 0.0454), although there was no significant correlation between 1,25D and serum albumin. Although there was no significant correlation between 25D and serum PTH, there was a significant, negative correlation between 1,25D and serum PTH (r = -0.379, p&amp;lt;0.001). Similarly, although there was no significant correlation between 25D and serum alkaline phosphatase, there was a significant, negative correlation between 1,25D and serum alkaline phosphatase (r = -0.309, p = 0.001). There were no significant differences in serum two vitamin D metabolites between patients with (n = 65) and without VDRA treatment, nor between those with (n = 12) and without calcimimetics. In a multiple regression analysis after adjustment of age, gender, haemodialysis duration, and VDRA treatment, serum 25D concentrations were significantly, independently associated with serum albumin (β = -0.244, p = 0.0149) (R2 = 0.125, p = 0.007). In a multiple regression analysis after the same adjustment, serum 1,25D concentrations were significantly, independently associated with serum intact PTH (β = -0.310, p = 0.003) (R2 = 0.200, p = 0.002). In the follow-up of three year, 16 patients died. Kaplan Meier analysis revealed that there tended to be better survival in patients with higher 25D concentration (n = 52) than those with lower concentration (p = 0.1936), although no significant association was seen between 1,25D and survival. Conclusion These results indicate that hypovitaminosis D (low 25D&amp;lt;30 ng/ml) is seen in all haemodialysis patients, and in most of these patients, serum 1,25D concentrations are low. Lower serum 25D concentrations are significantly associated with lower serum albumin, i.e., poorer nutritional status. Higher serum 1,25D, even in low ranges, is significantly associated with lower intact PHT and alkaline phosphatase, i.e. lower bone metabolism status. The results suggest that, in the era of new CKD-MBD treatments with calcimimetics and new VDRA, serum 25D may represent a nutritional status, and that serum 1,25D concentrations with regard to bone metabolism may be re-considered for the assessment of CKD-MBD, particularly in regards to prevention of secondary hyperparathyroidism.

Sexual dimorphisms in serum calcium and phosphate concentrations in the Rotterdam Study

Sex differences in serum phosphate and calcium have been reported but the exact nature and underlying regulatory mechanisms remain unclear. We aimed to compare calcium and phosphate concentrations between sexes, and explore potential covariates to elucidate underlying mechanisms of sex differences in a prospective, population-based cohort study. Pooled data of subjects > 45 years from three independent cohorts of the Rotterdam Study (RS) were used: RS-I-3 (n = 3623), RS-II-1 (n = 2394), RS-III-1 (n = 3241), with separate analyses from an additional time point of the first cohort RS-I-1 (n = 2688). Compared to men, women had significantly higher total serum calcium and phosphate concentrations which was not explained by BMI, kidney function nor smoking. Adjustment for serum estradiol diminished sex differences in serum calcium while adjustment for serum testosterone diminished sex differences in serum phosphate. Adjustment for vitamin D and alkaline phosphatase did not change the association between sex and calcium or phosphate in RS-I-1. In the sex-combined group, both serum calcium and phosphate decreased with age with a significant interaction for sex differences for serum calcium but not phosphate. In sex-stratified analyses, serum estradiol but not testosterone was inversely associated with serum calcium in both sexes. Serum estradiol was inversely associated with serum phosphate in both sexes to a similar degree, while serum testosterone was inversely associated with serum phosphate in both sexes with an apparent stronger effect in men than in women. Premenopausal women had lower serum phosphate compared to postmenopausal women. Serum testosterone was inversely associated with serum phosphate in postmenopausal women only. In conclusion, women > 45 years have higher serum calcium and phosphate concentrations compared to men of similar age, not explained by vitamin D or alkaline phosphatase concentrations. Serum estradiol but not testosterone was inversely associated with serum calcium while serum testosterone was inversely associated with serum phosphate in both sexes. Serum testosterone may in part explain sex differences in serum phosphate while estradiol could partly explain sex differences in serum calcium.

O117 Burosumab in the management of X-linked hypophosphataemia: a retrospective cohort study reviewing anthropometric and biochemical markers

Abstract Introduction Rickets is a bone disease caused by a defect in mineralization. When left untreated, it has lifelong Orthopaedic sequelae. Burosumab, an anti-fibroblast growth factor 23 monoclonal antibody, improves rickets severity, symptoms, and growth in children with X-linked hypophosphataemia (XLH) followed to 64 weeks in clinical trials. International dosing guidance recommends targeting normal serum phosphate concentration. However, some children may not achieve this despite maximal dosing. This study compares clinical outcomes in children with XLH on long-term burosumab treatment who achieved normal phosphate, vs those who did not. Methods Single-centre retrospective review of a large paediatric cohort with XLH treated with burosumab. We evaluated growth and biochemical markers of bone health in those who did compared to those who did not achieve normal plasma phosphate concentration. Results Fifty-five children with XLH with median age 11.7 [6.8–15.5] years were included. 27 (49%) had low plasma phosphate concentration, and 27 (49%) normal phosphate after a median burosumab treatment duration of 3.3 [IQR 2.6–3.7] years. 1 (2%) did not have a recent phosphate level recorded. No difference in growth was found between normal and abnormal phosphate groups (p = 0.9). A trend of superior growth in those with normal compared with abnormal alkaline phosphatase level was observed. Conclusion Young children with XLH experience sustained growth on long-term burosumab treatment, albeit without normal plasma phosphate concentration in many. Consideration should be made to changing burosumab dosing recommendations to target the normalisation of alkaline phosphatase instead of plasma phosphate concentration.

ASSOCIATION OF SERUM CALCIUM, SERUM PHOSPHATE AND SERUM VITAMIN D WITH SEVERITY OF CHRONIC LIVER DISEASE

Background: Chronic liver disease (CLD) is characterized by continuous decline in hepatic performance for over 6 months, that involves generation of coagulation factors, several other proteins, elimination of dangerous metabolic byproducts as well as bile elimination. In CLD, the serum phosphate concentrations change. According to the majority of research, it generally results in hypophosphatemia. It can have a variety of explanations, including internal rearrangement, reduced uptake, as well as excessive elimination. There is a connection between the metabolic activities of serum calcium, phosphate, as well as vitamin D. Comparatively fewer investigations have been conducted in subjects with CLD. Therefore, it is necessary to link or associate each of these to people who have CLD. Method: In this study, a total of 60 patients diagnosed with chronic liver disease were taken over a period of 6 months (Jan to June 2022). All relevant data were recorded and analyzed. Results: Among 60 patients, 45 percent of the patients belonged to the age group of 41 to 50 years. 78.33 percent of the patients were males while the remaining were females. Mean serum vitamin D levels, serum calcium and phosphate levels were found to be 23.42 ng/mL, 8.67 mg/dL and 3.12 mg/dL respectively. Conclusion: Vitamin D deciency is documented in the majority of patients aficted by CLD, particularly those having advanced disease. As the disease advances, the levels become lesser. However; serum calcium and phosphate levels doesn't show any signicant correlation with severity of disease.

Relationship between serum phosphate and mortality in critically ill children receiving continuous renal replacement therapy.

We aimed to explore the relationship between serum phosphate concentration and 90-day mortality in critically ill children receiving continuous renal replacement therapy (CRRT). Data from the medical records of children aged <13 years who received CRRT at the Pediatric Intensive Care Unit of Hunan Children's Hospital, China from January 2015 to June 2020 were retrospectively collected. Children were grouped into four categories according to the baseline phosphate concentration before CRRT and mean serum phosphate concentration during CRRT: <0.81 mmol/L (hypophosphatemia), 0.81-1.19 mmol/L, 1.2-2.4 mmol/L (normal phosphate concentration), and >2.4 mmol/L (hyperphosphatemia), with the normal phosphate group serving as the comparator group. The correlation of the serum phosphate concentration before and during CRRT with the 90-day mortality after CRRT initiation was analyzed using logistic regression. A total of 177 children were included in our study. The mean serum phosphate concentration before CRRT was 1.46 mmol/L (quartiles: 1.04, 2.20). The 90-day mortality rate was increased in children with a serum phosphate concentration >2.4 mmol/L before CRRT (adjusted odds ratio [aOR] 3.74, 95% confidence interval [CI] 1.42-9.86, P = 0.008). The mean serum phosphate concentration during CRRT was 1.2 mmol/L (quartiles: 0.91, 1.49). The 90-day mortality rate was increased in children with a mean serum phosphate concentration >2.4 mmol/L during CRRT (aOR 7.34, 95% CI 1.59-33.88, P = 0.011). Hyperphosphatemia before and during CRRT predicts a higher 90-day mortality rate.

Hepatic phosphate uptake and subsequent nerve-mediated phosphaturia are crucial for phosphate homeostasis following portal vein passage of phosphate in rats

Fibroblast growth factor 23, parathyroid hormone, and 1,25-dihydroxyvitamin D are critical in phosphate homeostasis. Despite these factors’ importance, regulators of phosphaturia in the acute postprandial phase remain largely unknown. This study investigated the mechanism of acute phosphate regulation in the postprandial phase in rats. Duodenal administration of radiolabeled phosphate (32P) showed that 32P levels in the inferior vena cava (IVC) blood were lower than those in the portal vein (PV) blood. Serum phosphate concentration transiently increased 5 min after phosphate solution administration through IVC, while it was maintained after the administration through PV. Phosphate administration through both IVC and PV resulted in increased fractional excretion of phosphate (FEPi) at 10 min without elevation of the known circulating factors, but urinary phosphate excretion during the period was 8% of the dose. Experiments using 32P or partial hepatectomy showed that the liver was one of the phosphate reservoirs. The elevation of FEPi and suppression of sodium-phosphate cotransporter 2a in the kidney at 10 min was attenuated in rats with SCH23390, hepatic denervation, or renal denervation, thus indicating that the liver communicated with the kidney via the nervous system to promote phosphaturia. These results revealed previously unknown mechanisms for serum phosphate maintenance.

Antiurolithiatic effect of a polyherbal formulation against sodium oxalate-induced urolithiasis in rats

BackgroundThe present study assesses the role of polyherbal formula (LACTN) against sodium oxalate (NaOx)—stimulated urolithiasis prophylactic and curative. Forty-eight rats were separated into the following regimen’s groups: Groups I, II, III, and IV (prophylactic groups). Group I (control group) received saline as vehicle. Group II (urolithiatic group) received 70 mg NaOx / kg b.wt, i.p. Groups III and IV received LACTN and cystone prophylactic (500 and 750 mg/kg b.wt, respectively) from 1st day to 7th day of urolithiasis induction. Groups V, VI, VII, and VIII (curative groups): these were divided into the prophylactic regimes, but LACTN and cystone were administered from 7th day to 14th day of urolithiasis induction.ResultsUrolithiatic rats co-/post-treated with LACTN and cystone elevated the urinary volume significantly (P < 0.05). Also, a significant decrease (P < 0.05) was observed in the serum and urine calcium and phosphate concentrations beside the increased magnesium value in urolithiatic rats co-/post-treated with LACTN. LACTN significantly (P < 0.05) ameliorates serum and urine creatinine, urea, and uric acid concentration. Moreover, urolithiatic rats co-/post-treated with LACTN significantly (P < 0.05) diminished MDA and increased GSH, GST, SOD, and CAT compared with urolithiatic rats.ConclusionsLACTN has anti-lithogenesis effect that may be due to its ability to remove the already presenting stone and/or to prevent the generation of extra calcium oxalate crystals. This action may be due to its components’ synergetic action that may provide encouraging combined formula to prevent/treat urolithiasis.

Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23

Fibroblast growth factor 23 (FGF23) was identified at the turn of the century as the long-sought circulating phosphatonin in human pathology. Since then, several clinical and experimental studies have investigated the metabolism of FGF23 and revealed its relevant pathogenic role in various diseases. Most of these studies have been performed in adult individuals. However, the mineral metabolism of the child is, to a large extent, different from that of the adult because, in addition to bone remodeling, the child undergoes a specific process of endochondral ossification responsible for adequate mineralization of long bones' metaphysis and growth in height. Vitamin D metabolism is known to be deeply involved in these processes. FGF23 might have an influence on bones' growth as well as on the high and age-dependent serum phosphate concentrations found in infancy and childhood. However, the interaction between FGF23 and vitamin D in children is largely unknown. Thus, this review focuses on the following aspects of FGF23 metabolism in the pediatric age: circulating concentrations' reference values, as well as those of other major variables involved in mineral homeostasis, and the relationship with vitamin D metabolism in the neonatal period, in vitamin D deficiency, in chronic kidney disease (CKD) and in hypophosphatemic disorders.

The Impact of Medical Nutrition Intervention on the Management of Hyperphosphatemia in Hemodialysis Patients with Stage 5 Chronic Kidney Disease: A Case Series

The treatment and interdisciplinary management of patients with chronic kidney disease (CKD) continue to improve long-term outcomes. The medical nutrition intervention's role is to establish a healthy diet plan for kidney protection, reach blood pressure and blood glucose goals, and prevent or delay health problems caused by kidney disease. Our study aims to report the effects of medical nutrition therapy-substituting foods rich in phosphorus-containing additives with ones low in phosphates content on phosphatemia and phosphate binders drug prescription in stage 5 CKD patients with hemodialysis. Thus, 18 adults with high phosphatemia levels (over 5.5 mg/dL) were monitored at a single center. Everyone received standard personalized diets to replace processed foods with phosphorus additives according to their comorbidities and treatment with prosphate binder drugs. Clinical laboratory data, including dialysis protocol, calcemia, and phosphatemia, were evaluated at the beginning of the study, after 30 and 60 days. A food survey was assessed at baseline and after 60 days. The results did not show significant differences between serum phosphate levels between the first and second measurements; thus, the phosphate binders' initial doses did not change. After 2 months, phosphate levels decreased considerably (from 7.322 mg/dL to 5.368 mg/dL); therefore, phosphate binder doses were diminished. In conclusion, medical nutrition intervention in patients with hemodialysis significantly reduced serum phosphate concentrations after 60 days. Restricting the intake of processed foods containing phosphorus additives-in particularized diets adapted to each patient's comorbidities-and receiving phosphate binders represented substantial steps to decrease phosphatemia levels. The best results were significantly associated with life expectancy; at the same time, they showed a negative correlation with the dialysis period and participants' age.

A preliminary report on the association between maternal serum organophosphate ester concentrations and gestational diabetes mellitus

Organophosphate esters (OPEs) are extensively manufactured and used in China. Whether exposure to OPEs during pregnancy increases the risk of gestational diabetes mellitus (GDM) is unknown. Between 2011 and 2012, a case-control study including 130 and 67 women with and without GDM, respectively, was conducted in Hangzhou, China. The levels of 10 OPEs in maternal serum samples at delivery were quantified, and the relationships between the OPE concentrations and GDM risk were investigated. The results show that in all participants, tri-n-butyl phosphate (TNBP, median: 2.02 ng/mL) was the most common OPE present in the serum, followed by tri-phenyl phosphate (TPHP, median: 1.74 ng/mL) and tri-iso-butyl phosphate (median: 1.68 ng/mL). With one-unit elevation in the tris (2-chloroethyl) phosphate, TNBP, TPHP, and tris (2-butoxy ethyl) phosphate (TBOEP) concentrations in maternal serum, 1-h glucose levels increased by 0.19 (95% confidence interval (CI): −0.01, 0.29), 0.11 (95% CI: −0.18, 0.62), 0.29 (95% CI: 0.12, 0.58), and 0.20 units (95% CI: 0.01, 0.44), respectively. In addition, a unit increase in TBOEP levels in maternal serum was associated with an increase of 0.26 units (95% CI: 0.09, 0.61) in 2-h glucose levels. After adjusting for covariate factors, serum TNBP (odds ratio (OR) = 2.07; 95% CI: 1.27, 3.41), TBOEP (OR = 2.63; 95% CI: 1.68, 4.11), and TPHP (OR = 1.03; 95% CI: 1.05, 1.51) concentrations were associated with GDM incidence in pregnant women. Overall, TNBP, TBOEP, and TPHP exposure during pregnancy is associated with GDM risk and increased glucose levels.

Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice.

Sarcopenia is defined by the progressive and generalized loss of muscle mass and function associated with aging. We have previously proposed that aging-related hyperphosphataemia is linked with the appearance of sarcopenia signs. Because there are not effective treatments to prevent sarcopenia, except for resistance exercise, we propose here to analyse whether the dietary restriction of phosphate could be a useful strategy to improve muscle function and structure in an animal model of aging. Five-month-old (young), 24-month-old (old) and 28-month-old (geriatric) male C57BL6 mice were used. Old and geriatric mice were divided into two groups, one fed with a standard diet (0.6% phosphate) and the other fed with a low-phosphate (low-P) diet (0.2% phosphate) for 3 or 7months, respectively. A phosphate binder, Velphoro®, was also supplemented in a group of old mice, mixed with a standard milled diet for 3months. Muscle mass was measured by the weight of gastrocnemius and tibial muscles, and quality by nuclear magnetic resonance imaging (NMRI) and histological staining assays. Muscle strength was measured by grip test and contractile properties of the tibialis muscle by electrical stimulation of the common peroneal nerve. Gait parameters were analysed during the spontaneous locomotion of the mice with footprinting. Orientation and motor coordination were evaluated using a static rod test. Old mice fed with low-P diet showed reduced serum phosphate concentration (16.46±0.77mg/dL young; 21.24±0.95mg/dL old; 17.46±0.82mg/dL low-P diet). Old mice fed with low-P diet displayed 44% more mass in gastrocnemius muscles with respect to old mice (P=0.004). NMRI revealed a significant reduction in T2 relaxation time (P=0.014) and increased magnetization transfer (P=0.045) and mean diffusivity (P=0.045) in low-P diet-treated mice compared with their coetaneous. The hypophosphataemic diet increased the fibre size and reduced the fibrotic area by 52% in gastrocnemius muscle with respect to old mice (P=0.002). Twitch force and tetanic force were significantly increased in old mice fed with the hypophosphataemic diet (P=0.004 and P=0.014, respectively). Physical performance was also improved, increasing gait speed by 30% (P=0.032) and reducing transition time in the static rod by 55% (P=0.012). Similar results were found when diet was supplemented with Velphoro®. The dietary restriction of phosphate in old mice improves muscle quantity and quality, muscle strength and physical performance. Similar results were found using the phosphate binder Velphoro®, supporting the role of phosphate in the impairment of muscle structure and function that occurs during aging.