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.

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.

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.

The Incidence and Risk Factors of Refeeding Syndrome-like Hypophosphatemia in Inflammatory Bowel Disease: A Preliminary Study.

BACKGROUND AND AIMS: Refeeding syndrome (RFS) is defined by the presence of acute electrolyte disturbances, including hypophosphatemia. Underlying disease(s), malnutrition and hospitalisation are known risk factors for RFS. It can occur in patients with inflammatory bowel disease (IBD). We aimed to determine the frequency of hypophosphatemia and the relationship between hypophosphatemia, disease severity and nutritional status in hospitalized patients with IBD. METHODS: This study was performed prospectively in hospitalized adult patients for the treatment of IBD in a tertiary-care hospital. Disease severity was assessed using Truelove and Witts score for ulcerative colitis (UC) and Crohn's Disease Activity Index for Crohn's disease (CD). Nutritional status was determined using Subjective Global Assessment (SGA). Serum phosphate concentration was recorded for first 7 days after hospitalization, and less than 0.65 mmol/l was defined as hypophosphatemia. RESULTS: Fifty participants (33 with UC and 17 with CD) were included in the study. The mean age of the study sample was 43.4±14.9 years, of which 64% were male. A total of 8.8% of patients with UC and 37.5% of patients with CD had severe (>moderate) disease upon study admission. Seventeen patients (34%) were malnourished. During the 7 study days, 23 participants (46%) had at least one episode of hypophosphatemia. Serum phosphate concentration was significantly and moderately correlated with serum potassium concentration in both the patients and the hypophosphatemia group on study day 3 (p<0.05). Multivariate logistic regression analysis showed that the presence of malnutrition [odds ratio (OR) = 3.64, 95% confidence interval (CI): 1.52-5.58, p=0.008), the administration of parenteral nutrition (OR=2.91, 95%Cl: 1.37-4.63, p=0.015), and severe IBD (OR=1.74, 95%CI: 1.03-3.42, p=0.020) were associated with hypophosphatemia. CONCLUSIONS: Approximately half of the participants exhibited at least one instance of hypophosphatemia during the study period. Hypophosphatemia was found to be associated with malnutrition, parenteral nutrition, and severe disease in patients with IBD requiring hospitalization.

Target Values for 25-Hydroxy and 1,25-Dihydroxy Vitamin D Based on Their Associations with Inflammation and Calcium-Phosphate Metabolism.

Target values for 25-hydroxy vitamin D and 1,25(OH)2D or 1,25-dihydroxy vitamin D remain a topic of debate among clinicians. We analysed data collected from December 2012 to April 2020 from two cohorts. Cohort A, comprising 455,062 subjects, was used to investigate the relationship between inflammatory indicators (white blood cell [WBC] count and C-reactive protein [CRP]) and 25(OH)D/1,25(OH)2D. Cohort B, including 47,778 subjects, was used to investigate the connection between 25(OH)D/1,25(OH)2D and mineral metabolism markers (phosphate, calcium, and intact parathyroid hormone [iPTH]). Quadratic models fit best for all tested correlations, revealing U-shaped relationships between inflammatory indicators and 25(OH)D and 1,25(OH)2D. Minimal CRP and WBC counts were observed at 1,25(OH)2D levels of 60 pg/mL and at 25(OH)D levels of 32 ng/mL, as well as of 42 ng/mL, respectively. iPTH correlated inversely with both 1,25(OH)2D and 25(OH)D, while phosphate as well as calcium levels positively correlated with both vitamin D forms. Calcium-phosphate product increased sharply when 25(OH)D was more than 50 ng/mL, indicating a possible risk for vascular calcification. Multiple regression analyses confirmed that these correlations were independent of confounders. This study suggests target values for 25(OH)D between 30-50 ng/mL and for 1,25(OH)2D between 50-70 pg/mL, based particularly on their associations with inflammation but also with mineral metabolism markers. These findings contribute to the ongoing discussion around ideal levels of vitamin D but require support from independent studies with data on clinical endpoints.

Intravenous ferric carboxymaltose is associated with lowering of plasma phosphate levels in patients with gastric bypass surgery: a retrospective case series.

AIMS: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass. METHODS: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering. RESULTS: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020). CONCLUSION: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.

Incidence and Risk Factors of Refeeding Syndrome in Preterm Infants.

This study aimed to evaluate the incidence and risk factors associated with refeeding syndrome (RFS) in preterm infants (≤32 weeks gestational age) during their first week of life. Infants (gestational age ≤ 32 weeks; birth weight < 1500 g) who were admitted to the neonatal intensive care unit (NICU), level III, and received parenteral nutrition between January 2015 and April 2024 were retrospectively evaluated. Modified log-Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the relative risk of risk factors. Of the 760 infants identified, 289 (38%) developed RFS. In the multivariable regression analysis, male, intraventricular hemorrhage (IVH), and sodium phosphate significantly affected RFS. Male infants had significantly increased RFS risk (aRR1.31; 95% CI 1.08-1.59). The RFS risk was significantly higher in infants with IVH (aRR 1.71; 95% CI 1.27-2.13). However, infants who received higher sodium phosphate in their first week of life had significantly lower RFS risk (aRR 0.67; 95% 0.47-0.98). This study revealed a notable incidence of RFS among preterm infants aged ≤32 gestational weeks, with sex, IVH, and low sodium phosphate as significant risk factors. Refined RFS diagnostic criteria and targeted interventions are needed for optimal management.

Effect of aluminum hydroxide on serum phosphate and fibroblast growth factor 23 concentrations in young adult cats with surgically induced chronic kidney disease.

OBJECTIVE: To describe serum fibroblast growth factor 23 (FGF-23) concentrations in young adult cats with remnant kidney model-induced chronic kidney disease (CKD) and to evaluate the effects of orally administered aluminum hydroxide (ALOH) on serum phosphate and FGF-23 concentrations in these cats. ANIMALS: 17 adult, purpose-bred cats with induced CKD and 13 healthy, age-matched cats. METHODS: A prospective, randomized study. Cats with induced CKD fed a wet renal diet received treatment with ALOH (90 mg/kg/d, PO) on days 0 to 42 and no treatment on days 43 to 84 (treatment group, n = 9) or no treatment on days 0 to 84 (control group, n = 8). Standard serum and urine biochemical analyses and several parameters reflective of calcium-phosphate balance, including serum parathyroid hormone and FGF-23 concentrations, were evaluated at baseline and various time points, including days 42 and 84. Age-matched, healthy, community-owned cats underwent similar evaluations at a single time point. Baseline data from CKD cats were compared to those of healthy cats. Longitudinal data from CKD cats were compared over time. RESULTS: Serum phosphate, total and ionized calcium, and FGF-23 concentrations were significantly higher in CKD cats at baseline relative to healthy cats (all P ≤ .009). Serum phosphate concentration did not change significantly over time in either CKD group; however, FGF-23 concentrations significantly increased over time in the control group (P < .02) but not the treatment group (P = .059). CLINICAL RELEVANCE: Aluminum hydroxide did not reduce serum phosphate or FGF-23 concentrations in this small study of cats with induced CKD chronically eating a phosphate-restricted diet.

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.

[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.

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.

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.

Dietary magnesium supplementation in cats with chronic kidney disease: A prospective double-blind randomized controlled trial.

BACKGROUND: Plasma total magnesium concentration (tMg) is a prognostic indicator in cats with chronic kidney disease (CKD), shorter survival time being associated with hypomagnesemia. Whether this risk factor is modifiable with dietary magnesium supplementation remains unexplored. OBJECTIVES: Evaluate effects of a magnesium-enriched phosphate-restricted diet (PRD) on CKD-mineral bone disorder (CKD-MBD) variables. ANIMALS: Sixty euthyroid client-owned cats with azotemic CKD, with 27 and 33 allocated to magnesium-enriched PRD or control PRD, respectively. METHODS: Prospective double-blind, parallel-group randomized trial. Cats with CKD, stabilized on a PRD, without hypermagnesemia (tMg >2.43 mg/dL) or hypercalcemia (plasma ionized calcium concentration, (iCa) >6 mg/dL), were recruited. Both intention-to-treat and per-protocol (eating ≥50% of study diet) analyses were performed; effects of dietary magnesium supplementation on clinicopathological variables were evaluated using linear mixed effects models. RESULTS: In the per-protocol analysis, tMg increased in cats consuming a magnesium-enriched PRD (ß, 0.25 ± .07 mg/dL/month; P < .001). Five magnesium supplemented cats had tMg >2.92 mg/dL, but none experienced adverse effects. Rate of change in iCa differed between groups (P = .01), with decreasing and increasing trends observed in cats fed magnesium-enriched PRD and control PRD, respectively. Four control cats developed ionized hypercalcemia versus none in the magnesium supplemented group. Log-transformed plasma fibroblast growth factor-23 concentration (FGF23) increased significantly in controls (ß, 0.14 ± .05 pg/mL/month; P = .01), but remained stable in the magnesium supplemented group (ß, 0.05±.06 pg/mL/month; P =.37). CONCLUSIONS AND CLINICAL IMPORTANCE: Magnesium-enriched PRD is a novel therapeutic strategy for managing feline CKD-MBD in cats, further stabilizing plasma FGF23 and preventing hypercalcemia.

Association Between the Serum Phosphate Levels and Hospital Mortality as Well as 90-Day Mortality Among Critically Ill Patients with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.

Purpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD. Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure. Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07-1.31, p<0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06-1.24, p<0.001). Compared to the medium group (Q2 ≥3.15, <4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08-2, p=0.013), and 1.31 (95% CI: 1.06-1.61, p=0.013) for 90-day mortality in the high group (Q3≥4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468-0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141-1.509, p<0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102-1.386, p<0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results. Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation.

Association between serum phosphate, magnesium, calcium and aortic valve sclerosis: a propensity score-matched case-control study.

OBJECTIVES: Aortic valve sclerosis has been proposed to signify greater cardiovascular risk; the correlation between serum trace elements and aortic valve sclerosis has been reported. Therefore, an in-depth exploration of the risk factors for aortic valve sclerosis and early intervention may reduce the risk of cardiovascular disease. METHODS: In this study, Patients with aortic valve sclerosis and non-aortic valve sclerosis who underwent echocardiographic diagnosis in the People's Hospital of Xinjiang Uygur Autonomous Region during the period from 2019 to 2021 were selected for this study. The correlation between aortic valve sclerosis and serum phosphorus, calcium, and magnesium levels was explored using the propensity score matching technique by pairing the two groups of patients 1:1. RESULTS: A total of 1,533 non-aortic valve sclerosis and 1,533 aortic valve sclerosis patients were included. Logistic regression analysis showed that serum magnesium [OR: 0.346; 95%CI: 0.227, 0.528] and serum calcium [OR: 7.022; 95%CI: 4.755, 10.369] were influential factors. Patients with low, intermediate, and high serum magnesium levels had a significantly lower risk of aortic valve sclerosis compared to patients with very low micronutrient levels (p < 0.05). Comparatively, patients with low or high serum calcium levels had an elevated risk of aortic valve sclerosis (p < 0.05). CONCLUSION: Serum magnesium may have a protective role against aortic valve sclerosis, while both low and high levels of serum calcium could be risk factor for the condition. These serum micronutrients may be indications of cardiovascular disease risk prediction or prevention, and more research is required.

Tenapanor improves long-term control of high phosphate concentrations in the blood in patients receiving maintenance dialysis: a plain language summary of the NORMALIZE study.

What is this summary about?This is a summary of an article that was published in the medical journal Kidney360 describing results from the NORMALIZE study. The NORMALIZE study looked at how well tenapanor tablets reduced higher-than-normal levels of phosphate in the blood of persons with kidney disease who are on maintenance dialysis. These persons are unable to keep their blood phosphate levels in a normal range, and high levels of phosphate can contribute to several serious health consequences.Tenapanor is approved as an add-on treatment for high levels of phosphate in the blood of adults with chronic kidney disease who are on maintenance dialysis and whose disease does not respond adequately to treatment with phosphate binders or who are not able to take phosphate binders. In earlier clinical studies, tenapanor was studied alone or studied together with phosphate binders. In a 1-year clinical study called PHREEDOM, researchers learned that when tenapanor was used alone, it lowered blood phosphate levels, and treated patients experienced acceptable safety and tolerability as determined by the doctors running the study. In the NORMALIZE study, adult patients took a 30-mg tenapanor tablet twice a day, either alone or with sevelamer, for up to 18 months after they completed the PHREEDOM study.What were the main conclusions reported by the researchers?The researchers found that one-third of patients taking tenapanor, either alone or with sevelamer, achieved normal blood phosphate levels. This is an improvement from the current standard of care with sevelamer alone to reduce blood phosphate levels. As seen in the earlier studies of tenapanor, the most common adverse event experienced by patients was softer or loose stools. No new safety concerns were reported in the NORMALIZE study.What are the key takeaways?The researchers concluded that tenapanor, used alone or combined with sevelamer, can be used long-term by adult patients receiving maintenance dialysis to reduce the phosphate levels in their blood to within the normal range. Patients who take tenapanor may experience softer or loose stools.This summary was developed by the authors to help adult patients with chronic kidney disease receiving dialysis, and their family members and/or caregivers, better understand the effects of taking tenapanor.[Box: see text]Link to original article here.