A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia.

OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.

Daily versus fortnightly oral vitamin D3 in treatment of symptomatic vitamin D deficiency in children aged 1-10 years: An open labelled randomized controlled trial.

OBJECTIVE: Compare the efficacy and safety of daily versus fortnightly oral vitamin D3 in treating symptomatic vitamin D deficiency in children aged 1-10 years. DESIGN: Open labelled randomized controlled trial. PATIENTS: Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D3, 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day. MEASUREMENTS: Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens. RESULTS: Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range, with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p -0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up. CONCLUSIONS: Daily and fortnightly oral vitamin D3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio.

Clinical Characteristics, Therapeutic Options, and Outcomes in Hyperphosphatemic Tumoral Calcinosis: A Systematic Review.

This systematic review was performed to understand better the myriad presentations, various therapeutic options, response to therapy, and its clinical outcomes in hyperphosphatemic tumoral calcinosis (HTC). Full texts were selected according to strict inclusion criteria. All case reports of HTC wherein baseline phosphate was measured, treatment offered was mentioned, and information on follow-up and response to therapy that were available were included. A total of 43 of 188 eligible studies (N = 63 patients) met the inclusion criteria. A list of desired data was extracted and graded for methodological quality. A total of 63 individuals (Males = 33) were included from the 43 eligible case studies. The median age of the patients was 18 (IQR 8-32) years. The most frequently involved sites were the hip/gluteal region (34/63; 53.9%) followed by the elbow/forearm (26/63; 41.2%), and the shoulder (18/63; 28.5%). Three patients had conjunctival calcific deposits. The mean (SD) phosphate was 6.9 (1.1) mg/dL. Among the subjects, 36/63 (57.1%) underwent surgical excision with some form of medical therapy. Two patients underwent only surgical excision (2.1%). One patient was maintained on follow-up (1.6%) and 24/63 (38.1%) patients were treated with medical measures. The median (IQR) follow-up duration was 3 (1-9) years. Regression or reduction in lesion size was reported in 19/63 (30.2%) subjects; 20/63 (31.7%) showed progression, 24/63 (38.1%) had features of stable disease, and mortality was reported in 3 patients (4.7%). We report for the first time a detailed description of the clinical and therapeutic response of HTC. A combination of medical measures aimed at lowering serum phosphate appears to be the cornerstone of treatment, although clinical responses may vary.

Burosumab Efficacy and Safety in Patients with X-Linked Hypophosphatemia: Systematic Review and Meta-analysis of Real-World Data.

To assess the efficacy and safety of burosumab in children and adults with X-linked hypophosphatemia based on real-world evidence. MEDLINE (via PubMed) and Cochrane Library were searched until 18 October 2023 for single-arm (before-after) studies. Registries including Clinicaltrials.gov, EU Clinical Trials, WHO International Clinical Trials Registry Platform, and conference abstracts. The outcomes were a change in serum phosphorus concentrations and change in RSS, a change in serum ALP, bone-specific ALP, a change in the ratio of Tubular maximum reabsorption of Phosphate to Glomerular Filtrate rate, a change in serum 1,25(OH)2D and 25(OH)2D concentrations, change in height Z-score, McMaster Universities Osteoarthritis Index (WOMAC) and safety outcomes. An inverse variance random-effects meta-analysis was applied for data synthesis. Fifteen studies (289 participants) were included. Burosumab treatment improved serum phosphate concentrations [mean difference 0.88 mg/dl, 95% confidence interval 0.70 to 1.07, I2 = 92%), Rickets Severity score (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I2 = 71%), serum alkaline phosphate concentrations (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I2 = 71%), serum 1,25(OH)2D concentrations (mean difference 18.91 pg/ml, 95% confidence interval 6.39 to 31.43, I2 = 96%) and renal phosphate reabsorption (mean difference 1.22 mg/dl, 95% confidence interval 0.70 to 1.74, I2 93%). Burosumab treatment improved overall clinical and laboratory findings in patients with X-linked hypophosphatemia.

Mitochondrial phosphate-carrier deficiency mimicking infantile-onset Pompe disease.

The mitochondrial phosphate carrier is critical for adenosine triphosphate synthesis by serving as the primary means for mitochondrial phosphate import across the inner membrane. Variants in the SLC25A3 gene coding mitochondrial phosphate carrier lead to failure in inorganic phosphate transport across mitochondria. The critical dependence on mitochondria as an energy source is especially evident in tissues with high-energy demands such as the heart, muscle; defects in the mitochondrial energy production machinery underlie a wide range of primary mitochondrial disorders that present with cardiac and muscle diseases. The characteristic clinical picture of a prominent early-onset hypertrophic cardiomyopathy and lactic acidosis may be an indication for analysis of the SLC25A3 gene. Here, described a patient with suspicion of infantile Pompe disease due to involvement of heart and muscle and high-level of plasma creatinine kinase but finally diagnosed mitochondrial phosphate-carrier deficiency.

Tolerability, safety and efficacy of a novel phosphate binder VS-505 (AP301): a Phase 2 dose-escalation and dose-ranging study in patients undergoing maintenance hemodialysis.

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. CLINICAL TRIAL REGISTRATION NUMBER: NCT04551300 .

The Association Between Low Preoperative Phosphate Levels and Postliver Surgery Outcomes-A Single Center Experience.

INTRODUCTION: Previous research has demonstrated the impact of postoperative phosphate levels on liver regeneration and outcomes after liver resection surgeries, a potential predictor for regenerative success and liver failure. However, little is known about the association between low preoperative serum phosphate levels and outcomes in liver resections. METHODS: We performed a retrospective analysis of liver resections performed at our institution. Patients were categorized based on preoperative phosphate levels (low versus normal). Our primary outcome measure was posthepatectomy liver failure. RESULTS: A total of 265 cases met the study criteria. 71 patients (26.7%) had low preoperative phosphate levels. The incidence of posthepatectomy liver failure was higher in the low preoperative phosphate group (19.2% versus 12.4%). However, after propensity score matching, rates of posthepatectomy liver failure were similar between low and normal preoperative phosphate cohorts (13% versus 14%, P = 0.83). CONCLUSIONS: Low preoperative phosphate levels were not associated with worse postoperative outcomes in this study. Further studies are warranted to investigate this association and its relevance as a clinical prognostic factor for postoperative liver failure.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Antenatal presentation and early postnatal treatment of infantile hypercalcemia type 2.

Infantile hypercalcemia (IH) is a rare genetic disorder characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis during the first months of life. Biallelic variants in the genes CYP24A1 and SCL34A1 cause IH1 and 2, respectively. We present the case of a newborn with an antenatal diagnosis of IH2 due to the identification of echogenic, yet normal-sized kidneys at 23 weeks gestation. Trio whole-exome sequencing initially identified only a heterozygous pathogenic variant in SLC34A1. Re-analysis of the exome data because of the clinical suspicion of IH2 revealed a 21-basepair deletion in trans that had initially been filtered out because of its high allele frequency. The diagnosis of IH2 enabled postnatal screening for hypercalcemia, present already at week 1, resulting in early treatment with phosphate supplementation and vitamin D avoidance. In the subsequent course, biochemical parameters were normalized, and the patient showed no obvious clinical complications of IH2, apart from the nephrocalcinosis.

The association between serum phosphate and length of hospital stay and all-cause mortality in adult patients: a cross-sectional study.

BACKGROUND: Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients. METHODS: This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64-0.8 mmol/L; G3, iP 0.8-1.16 mmol/L; G4, iP 1.16-1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records. RESULTS: A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An "L-shaped" non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4. CONCLUSIONS: Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention.

Determination of Reference Intervals of Some Biochemistry Tests by the Bhattacharya and Hoffmann Methods.

BACKGROUND: Clinical laboratory tests are being evaluated with reference intervals (RI). Therefore, it is important that each laboratory determines and classifies its own reliable RI for each test to ensure an accurate and effective interpretation. The proposed method for determining RI is the "direct" approach, but it is a difficult, troublesome, time-consuming, and expensive method. An alternative approach is the "indirect" approach. In this study, we aimed to compare the RI values determined by the indirect method from the Calcium (Ca), Magnesium (Mg), Phosphate (P), 25-Hydroxy Vitamin D (25(OH)D), and Parathyroid hormone (PTH) test results with the RI provided by the manufacturer. METHODS: A total of 1,520,314 Ca, Mg, P, 25(OH)D, and PTH test results, which were studied in our laboratory between January and November 2022, were included in the study. Data cleaning was done for individuals between the ages of 18 - 89, and only one record was allowed. The Tukey method was used to determine and exclude extreme values. Ca and Mg tests were divided into age groups (18 - 59 and 60 - 89 years), P, 25(OH)D, and PTH tests were divided into female - male groups. RI was calculated by using the Bhattacharya and Hoffmann methods. CLIA 19 acceptable limits were used to evaluate the compliance with the manufacturer's RI. RESULTS: The RI results obtained by applying the Bhattacharya and Hoffmann methods were found to be significantly consistent and compatible with each other. According to the manufacturer's RI, Ca and Mg were compatible with RI in both methods, P was considered compatible with PTH and 25(OH)D upper reference limit in the Bhattacharya method, P was considered compatible with 25(OH)D lower reference limit and PTH upper reference limit in the Hoffmann method, while 25(OH)D lower reference limit was found to be different in the Bhattacharya method, and 25(OH)D upper reference limit and PTH lower reference limit were found to be different in the P male group in the Hoffmann method. CONCLUSIONS: We believe that it is of great importance for each laboratory to determine the RI specific for the population they serve and to choose the analytical method they use according to age and gender while periodically updating them to interpret the test results correctly.

Calcium/phosphate ratio: an additional tool for the clinical management of asymptomatic primary hyperparathyroidism?

PURPOSE: Serum calcium/phosphate ratio (Ca/P) has been recently proposed as an additional tool to identify primary hyperparathyroidism (PHPT), especially in patients with subclinical presentation, with a proposed cut-off of 3.3 when both values are expressed in mg/dL. No data are available on the relationship between Ca/P and the clinical presentation of PHPT. We thus evaluated this relationship in a large, single-center, unselected series. METHODS: 515 consecutive PHPT patients (mean age 65 ± 13.15 years, 77.1% females) were retrospectively evaluated at diagnosis. RESULTS: Mean Ca/P was 4.54 ± 1.5 (range 2.36-13.9), being higher than 3.3 in 88.5% of patients. Ca/P was significantly higher in (1) males, (2) symptomatic PHPT, (3) patients with 25-hydroxy vitamin D levels lower than 20 µg/L, (4) patients with osteitis fibrosa cystica, (5) patients with T score < - 2.5 at the radial site. In a multivariate regression analysis, Ca/P resulted significantly associated with PTH levels. After the exclusion of 57 patients with asymptomatic PHPT (aPHPT) patients and serum Ca higher than 1 mg/dL above the upper limit of normal range, no differences were found in Ca/P between aPHPT meeting or not surgical criteria. CONCLUSIONS: In PHPT Ca/P ratio is associated with increased biochemical and clinical severity of disease and represents a direct indicator of clinical bone damage. However, it does not seem an additional tool to identify aPHPT patients reaching surgical indication.

Diurnal fluctuations in biochemical parameters related to calcium homeostasis - the Bispebjerg study of diurnal variations.

PURPOSE: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications. PATIENTS AND METHODS: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p < 0.05. RESULTS: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%. CONCLUSION: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.

Effect of a plant protein-rich diet on postprandial phosphate metabolism in healthy adult men: a randomised controlled trial.

BACKGROUND: This study examined the effects of animal protein- and plant protein-rich diets on postprandial phosphorus metabolism in healthy male subjects. METHODS: The study was conducted by randomised parallel-group comparison of healthy men aged 21-24 years. In Study 1, participants were divided into two groups and consumed either a 70% animal protein diet (AD, n = 6) or a 70% plant protein diet (PD, n = 6). In Study 2, participants were divided into three groups and consumed either AD (n = 10), PD (n = 10) or AD + DF, a 70% animal protein diet loaded with the same amount of fibre as PD (n = 9). The phosphorus contents of the diets used in this study were nearly equivalent (AD, 710.1 mg; PD, 709.7 mg; AD + DF, 708.9 mg). Blood and urine samples were collected before, and 2 and 4 h after the meal to measure phosphorus and calcium levels. RESULTS: In Study 1, PD consumption resulted in lower blood and urinary phosphorus concentrations 2 h postprandially compared with AD (p < 0.05). In Study 2, blood phosphorus levels in AD + DF after the diet remained lower, but not significantly so compared with AD, and urinary phosphorus levels were significantly lower 2 h postprandially (p < 0.05). CONCLUSIONS: A plant protein-rich diet reduced rapid postprandial increases in blood and urinary phosphorus concentrations compared with the animal protein-rich diets, suggesting that dietary fibre may play a partial role in the postprandial decreases in blood and urinary phosphorus concentrations.

The Effect of Niacinamide Supplementation on Phosphate Concentrations in Dutch Dialysis Patients: A Randomized Crossover Trial.

OBJECTIVE: Hyperphosphatemia is a common complication in patients with kidney failure, despite the use of phosphate binders. Vitamin B3, either in the form of niacin or niacinamide (NAM), shows potential as "add-on" treatment to reduce serum phosphate concentrations in this population. NAM seems to lack many of the side effects that are observed with niacin. The aim of this study was to investigate whether NAM is an effective and acceptable treatment in reducing serum phosphate concentrations in patients with kidney failure. METHODS: DiaNia was a double-blind placebo-controlled randomized crossover trial, comparing NAM (250-500 mg/day) to placebo as "add-on" treatment to an individual treatment with approved phosphate binders for 12 weeks in patients receiving hemodialysis. The primary outcome was serum phosphate concentrations, and the secondary outcomes were platelet counts as well as drop-outs due to side effects. Data were analyzed using both per-protocol and intention-to-treat analyses. RESULTS: Mean age of the per-protocol population (n = 26) was 63.6 ± 17.2 years and 53.8% were men. NAM treatment significantly reduced serum phosphate with 0.59 mg/dL (p = .03). Linear mixed-effects models demonstrated superiority of 12 weeks NAM over 12 weeks placebo with a between-treatment difference of 0.77 mg/dL (95% CI 0.010, 1.43; P = .03). Similar results, although not significant, were found in the intention-to-treat population. We found no between-treatment differences in platelet counts and during the NAM treatment we observed 3 drop-outs due to side effects (8.6%). CONCLUSION: NAM is effective in reducing serum phosphate concentrations in patients with kidney failure receiving hemodialysis. In addition, NAM is well-tolerated and seems not to increase the risk of thrombocytopenia. Thus, NAM can be valuable as "add-on" treatment to combat hyperphosphatemia in patients with kidney failure. However, more research in larger populations is needed to confirm this.

Efficacy and safety of tenapanor in end-stage renal disease patients with hyperphosphatemia: a systematic review and meta-analysis.

BACKGROUND: Hyperphosphatemia occurs universally in end-stage renal disease(ESRD), and the attainment of target serum phosphate levels remains suboptimal with currently available phosphate binders. This meta-analysis aimed to evaluate the efficacy and safety of tenapanor in end-stage renal disease patients with hyperphosphatemia. METHODS: Data sources included PubMed, Embase, Web of Science, and Cochrane Library. This meta-analysis included randomized controlled trials evaluating both the efficacy of tenapanor in reducing serum phosphate levels and its safety profile. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. The GRADE system was used to assess the overall certainty of evidence. A meta-analysis was carried out by using fixed effects (I2 values < 50%) or random effects (I2 values ≥ 50%) models to calculate MD with 95% CI for continuous outcome variables and RR with 95% CI for dichotomous variables. Publication bias was evaluated using funnel plots. RESULTS: A total of seven RCTs involving 877 individuals were included. The pooling analysis demonstrates that the reduction in mean serum phosphorus levels in the tenapanor group was significantly greater than that in the placebo group [MD= -1.06 mg/dl, 95% CI (-1.59, -0.53); I2 = 83%, p < 0.0001]. The proportion of patients achieving a serum phosphorus level of < 5.5 mg/dL, along with the incidence of any adverse events (AEs) and gastrointestinal disorders, was higher in the tenapanor group compared to the placebo group. CONCLUSION: Tenapanor has the potential to significantly reduce serum phosphorus levels and enhance the rate of achieving target levels compared to placebo, all while maintaining an acceptable safety and tolerability profile. REGISTRATION: PROSPERO registration number CRD42024544531.

Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice.

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3-/-). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3-/-, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.

Effect of Dietary Phosphate Restriction in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphataemia in Southern Nigeria.

BACKGROUND: Hyperphosphataemia is a common cardiovascular risk factor in chronic kidney disease (CKD). Dietary counseling and control are key aspects in the management of CKD. Although some studies have shown the beneficial effects of dietary phosphate restriction on cardiovascular and bone health in haemodialysis patients, little is known about its effect in pre-dialysis CKD patients. AIM: To determine the effect of dietary phosphate restriction in predialysis CKD patients with hyperphosphataemia. METHODS: A hospital-based interventional study involving 72 predialysis CKD patients with hyperphosphataemia randomly allocated into 2 groups. Group 1 had nutritional counseling on dietary phosphate restriction while group 2 had no form of dietary phosphate restriction. All participants were placed on a phosphate binder throughout the study period of 3 months. At the end of the third month, a repeat of baseline tests (serum phosphate, calcium, albumin, creatinine and serum lipids) and anthropometric measurements were done and compared between the 2 groups. RESULTS: The mean age in the treatment and control groups were 54.6±14.7 years and 54.9±14.5 years, respectively. The mean serum phosphate (5.7±0.5 vs. 5.5± 0.4mg/dl), calcium (7.9±0.9 vs. 7.8± 0.7mg/dl), albumin (3.8±0.4 vs. 3.9±0.7g/dl), creatinine (3.9±1.3 vs. 3.7±1.2mg/dl) and body mass index (BMI) (25.0±3.9 vs.25.4±3.1kg/m2) were similar in both groups. Serum phosphate, potassium, fasting blood glucose (FBG), total cholesterol, triglycerides and BMI were significantly reduced while there was no significant change in serum calcium-phosphate product and haematocrit following dietary phosphate restriction in addition to use of phosphate binders. However, on comparison of the changes between the treatment and control groups preand post- intervention, there was no significant change in serum phosphate but there was significant decrease in serum potassium, triglyceride and FBG. CONCLUSION: The use of phosphate binders in pre-dialysis CKD significantly reduced serum phosphate while additional dietary phosphate restriction had no significant effect on serum phosphate lowering and there was no significant change in nutritional status in predialysis CKD patients with hyperphosphataemia.

CONTEXTE: L'hyperphosphatémie est un facteur de risque cardiovasculaire courant dans la maladie rénale chronique (MRC). Le conseil et le contrôle diététiques sont des aspects clés dans la gestion de la MRC. Bien que certaines études aient montré les effets bénéfiques de la restriction alimentaire en phosphate sur la santé cardiovasculaire et osseuse chez les patients en hémodialyse, peu est connu sur son effet chez les patients atteints de MRC pré-dialyse. OBJECTIF: Déterminer l'effet de la restriction alimentaire en phosphate chez les patients atteints de MRC pré-dialyse avec hyperphosphatémie. MÉTHODES: Étude interventionnelle hospitalière impliquant 72 patients atteints de MRC pré-dialyse avec hyperphosphatémie, répartis aléatoirement en 2 groupes. Le groupe 1 a reçu des conseils nutritionnels sur la restriction alimentaire en phosphate tandis que le groupe 2 n'a reçu aucune forme de restriction alimentaire en phosphate. Tous les participants ont été mis sous un chélateur de phosphate pendant toute la période d'étude de 3 mois. À la fin du troisième mois, les tests de base (phosphate sérique, calcium, albumine, créatinine et lipides sériques) et les mesures anthropométriques ont été répétés et comparés entre les 2 groupes. RÉSULTATS: L'âge moyen dans les groupes traitement et contrôle était respectivement de 54,6±14,7 ans et 54,9±14,5 ans. Les moyennes du phosphate sérique (5,7±0,5 contre 5,5±0,4 mg/dl), du calcium (7,9±0,9 contre 7,8±0,7 mg/dl), de l'albumine (3,8±0,4 contre 3,9±0,7 g/dl), de la créatinine (3,9±1,3 contre 3,7±1,2 mg/dl) et de l'indice de masse corporelle (IMC) (25,0±3,9 contre 25,4±3,1 kg/m2) étaient similaires dans les deux groupes. Le phosphate sérique, le potassium, la glycémie à jeun (GAJ), le cholestérol total, les triglycérides et l'IMC ont été significativement réduits, tandis qu'il n'y avait aucun changement significatif dans le produit calcium-phosphate sérique et l'hématocrite suite à la restriction alimentaire en phosphate en plus de l'utilisation de chélateurs de phosphate. Cependant, en comparant les changements entre les groupes traitement et contrôle avant et après l'intervention, il n'y avait pas de changement significatif du phosphate sérique, mais il y avait une diminution significative du potassium sérique, des triglycérides et de la GAJ. CONCLUSION: L'utilisation de chélateurs de phosphate chez les patients atteints de MRC pré-dialyse a significativement réduit le phosphate sérique, tandis que la restriction alimentaire en phosphate supplémentaire n'a eu aucun effet significatif sur la réduction du phosphate sérique et il n'y avait aucun changement significatif de l'état nutritionnel chez les patients atteints de MRC pré-dialyse avec hyperphosphatémie. MOTS-CLÉS: Maladie rénale chronique, Pré-dialyse, Hyperphosphatémie, Restriction alimentaire.

Prevalence and Risk Factors of Vitamin D, Calcium and Phosphate Deficiency among Apparently Healthy Children Aged 6-24 Months in a Semi-urban Community in Southwest, Nigeria.

BACKGROUND: Adequate levels of calcium, phosphate and Vitamin D are essential for bone physiology and growth, as well as preventing some common childhood illnesses. This study aimed to determine the prevalence of the deficiencies of these nutrients and factors affecting their serum levels in Nigerian children. METHODS: This was a cross-sectional study that involved 220 apparently healthy children aged 6-24 months in Ikenne Local Government Area of Ogun State, Nigeria. Serum calcium and phosphate were assayed using the calorimetric method, while Vitamin D (25-OH Vitamin D) was assayed with ELISA. RESULTS: The mean (±standard deviation [SD]) serum Vitamin D level was 55.07 ± 16.53 ng/ml, while the mean (±SD) serum calcium and phosphate were 2.27 ± 0.13 mmol/l and 1.28 ± 0.18 mmol/l, respectively. Eleven (5%) of the children had hypovitaminosis D, 23 (10.5%) had hypocalcaemia and 12 (5.5%) had hypophosphataemia. Factors found to be significantly associated with hypovitaminosis D included low consumption of milk and the use of a hijab veil, while malnutrition (both undernutrition and overnutrition) was significantly associated with hypocalcaemia. CONCLUSION: The prevalence levels of hypovitaminosis D and hypophosphataemia were low, while hypocalcaemia was more common. Low milk consumption and use of a hijab veil were risk factors for hypovitaminosis D, while malnutrition was a risk factor for hypocalcaemia. Malnourished children, especially overnourished ones, should be routinely screened for hypocalcaemia because of its high prevalence among them.

[Retrospective study on the diagnosis, treatment, and follow-up of 85 cases of hypophosphatemic rickets in children]. / 85ä¾‹ä½Žè¡€ç£·æ€§ä½å»ç— æ‚£å„¿è¯Šæ–­ã€æ²»ç–—ä¸Žéšè®¿çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients. METHODS: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022. RESULTS: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs (P<0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease (P<0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis (OR=1.740, P<0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42). CONCLUSIONS: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682.