Calcium-phosphate Product Research Articles

Associations of Cognitive Function with Serum Magnesium and Phosphate in Hemodialysis Patients: A Cross-Sectional Analysis of the Osaka Dialysis Complication Study (ODCS)

Cognitive impairment and dementia are common in patients with chronic kidney disease, including those undergoing hemodialysis. Since magnesium and phosphate play important roles in brain function and aging, alterations in these and other factors related to bone mineral disorder (MBD) may contribute to low cognitive performance in patients on hemodialysis. This cross-sectional study examined the associations between cognitive function and MBD-related factors among 1207 patients on maintenance hemodialysis. Cognitive function was assessed by the Modified Mini-Mental State examination (3MS). The exposure variables of interest were serum magnesium, phosphate, calcium, calcium–phosphate product, intact parathyroid hormone, fetuin-A, T50 calciprotein crystallization test, use of phosphate binders, use of cinacalcet, and use of vitamin D receptor activators. Multivariable-adjusted linear regression models were used to examine the associations between 3MS and each of the exposure variables independent of 13 potential non-mineral confounders. We found that lower 3MS was associated with lower serum magnesium, lower phosphate, lower calcium–phosphate product, and nonuse of phosphate binders. These results suggest that magnesium and phosphate play potentially protective roles against cognitive impairment in this population.

Pseudocalcinosis Tumorale (Teutschlander Disease) in Chronic Hemodialysis Patients

Pseudotumoral calcinosis (CPT) is a condition characterized by the deposition of calcium phosphate crystals in the periarticular tissues, forming large calcified masses. Although the pathophysiology of CPT is not fully understood, an increase in the calcium-phosphate product beyond the precipitation threshold and severe hyperparathyroidism appear to play a significant role. Treatment remains controversial, with surgical excision often recommended. We report a case of CPT in a 74-year-old diabetic patient undergoing chronic hemodialysis who experienced progressively worsening pain in the left hip for six months, along with mobility difficulties. A CT scan revealed a calcified mass on the posterior thigh, likely explaining the electric shock-like pain, as well as compression of the superficial femoral artery causing decubitus pain resembling critical limb ischemia. The biological assessment showed elevated calcium-phosphate levels and hyperparathyroidism. Surgical excision is not indicated due to the mass’s proximity to vascular and nerve structures. This case highlights the diagnostic and therapeutic challenges of CPT, emphasizing the need for iterative angioplasties, considering that this condition is rare in chronic hemodialysis patients with calcified periarticular masses.

8749 Skeletal effects among pre and postmenopausal women with hypoparathyroidism (HypoPT); data from the Canadian National Hypoparathyroidism Registry (CNHR)

Abstract Disclosure: H. AbuAlrob: None. S. Hussein: None. H. Afifi: None. D.S. Ali: None. A. Almoulia: None. D. Bole: None. M. Braga: None. P. Chandra: None. A. Cheng: None. R. Cheung: None. J.E. Young: None. J. Hetal: None. S. Khan: None. T.S. Khan: None. J. Malhem: None. H. Malik: None. S. Mehmood: None. A. Millar: None. E. Morgante: None. F. Naveed: None. H. Niazi: None. T.L. Paul: None. A. Prebtani: None. Z. Punthakee: None. J.A. Shaban: None. R. Shah: None. M. Shrayyef: None. M. Shaikh: None. C. Tagra: None. S.R. Teschke: None. I.T. Tauqir: None. S. Van Uum: None. W. Robert: None. M. Ovize: Employee; Self; Amolyt. A.A. Khan: Research Investigator; Self; Amolyt, Ascend Therapeutics (A Besins Healthcare company), Takeda. Introduction: the CNHR registry was established in 2014 with the objectives of identifying the etiology, presentation, natural history and current treatment of hypoPT[1]. Methods: 101 patients with hypoPT were included in this prospective study. Patients completed baseline assessments including 3 site bone mineral density (BMD), trabecular bone score (TBS), fracture risk assessments, and bone biomarkers. Baseline data is presented. Results: A total of 101 participants were enrolled, 83 (82%) were female, and 18 (18%) were male. There were 35 (42%) premenopausal females and 48 (58%) postmenopausal females (PMF). Only PMF were on antiresorptive therapy. Seven (7/8) were on bisphosphonate therapy (i.e., alendronate), and 3 females were on denosumab. Among premenopausal females the average corrected calcium (Ca) was 2.03 mmol/L (SD=0.26), calcium phosphate product (Ca PO4) was 2.75 (SD=0.62), and the eGFR 94.63 mL/min (SD=18.08). The average bone turnover markers among premenopausal women for the Telopeptide-C (CTX) was 242.4 ng/L (SD=209.4) (CTX within the reference range (WRR) 136-689 ng/L) while the Propeptide 1 Collagen (P1NP) was 37.6 ug/L (SD=39.2) (P1NP WRR 19-83 ug/L). Among PMF, the average corrected Ca was 2.22 mmol/L (SD=0.18), Ca PO4 was 2.14 (SD=0.17), and the eGFR 73.9 mL/min (SD=23.0). The average bone turnover markers among PMF for CTX was 346.1 ng/L (SD=488.4) (WRR 177-1015 ng/L) while P1NP was 47.1 ug/L (SD=33.1) (WRR 16-98 ug/L). Among premenopausal women (n=35), the mean total hip Z-score was 0.87 (SD=1.29), L1-L4 Z-score 0.98 (SD=1.19), FN Z-score 0.59(SD=1.17), and 1/3R Z-score -0.04 (SD=0.77). Among PMF (n=48) the mean total hip T-score was -0.20 (SD=1.65), L1-L4 T-score -0.24 (SD=1.88), FN T-score -0.43(SD=1.59), and 1/3R T-score -0.94(SD=1.23).TBS scores in premenopausal women were normal (TBS=1.41 (SD=0.10)) however the TBS was partially degraded among PMF (TBS= 1.28(SD=0.15)). Fracture data has previously been reported3. Conclusion: The effects of hypoPT on bone strength needs further study2. Our data suggests that bone quality maybe impaired in PMF with hypoPT as noted by the presence of degraded TBS scores and the presence of fragility fracture in this population. Reference 1.Khan AA et al Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada. Endocrine 2021. 2.Khan AA et al JBMR 2022 Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop3.Hussein S et al. Skeletal effects of hypoparathyroidism (HypoPT); data from the Canadian National Hypoparathyroidism Registry (CNHR). Available here: https://amolytpharma.com/wp-content/uploads/2023/10/ASBMR-CNHR_FINAL.pdf Presentation: 6/2/2024

Prevalence of coronary artery calcification in patients with end-stage renal disease undergoing dialysis and the association of various risk factors with the development of coronary artery calcification in this patient population

Background: Patients with end-stage renal disease (ESRD) on dialysis exhibit a significantly higher risk of coronary artery calcification (CAC) than age-matched normal individuals, contributing to elevated cardiovascular morbidity and mortality. Aims and Objectives: This study designed to assess the prevalence of CAC in ESRD patients on dialysis and identify associated risk factors. Materials and Methods: Fifty ESRD patients undergoing maintenance dialysis and twenty normal subjects were included in this cross-sectional observational study. Serum calcium, phosphate, and parathyroid hormone were measured in all ESRD patients and normal controls. Multi Row Spiral Computed Tomography was performed to determine CAC scoring (CACS). Results: CACS was significantly higher in ESRD patients compared to normal subjects (mean CACS: 91.4±32.7 vs. 7.75±9.5 Agatston units, P<0.05). Elevated levels of calcium phosphate products, serum leptin, intact parathyroid hormone (iPTH), presence of diabetes mellitus, and longer duration of dialysis were correlated with increased incidence of CACS in ESRD patients, as indicated by higher odd’s ratios ranged from 1.10 to 6.93. Conclusion: CAC is highly prevalent in ESRD patients on dialysis, emphasizing the need for stringent risk factor management. Our findings suggest that controlling calcium phosphate product, serum leptin, age, iPTH levels, and duration of dialysis may reduce CAC burden in this population, potentially mitigating cardiovascular risk and improving outcomes.

Long-Term Efficacy and Safety of Upacicalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: Open-Label 52-Week Study

Plain Language SummaryCalcimimetics are widely used for the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. However, conventional calcimimetics have risks of upper gastrointestinal disturbances and hypocalcemia. Upacicalcet, a novel intravenous calcimimetic, is expected to reduce these risks. To assess the long-term efficacy and safety of upacicalcet, a phase 3 open-label, 52-week study in HD patients with SHPT was conducted in Japan. A total of 157 Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Of those, 138 completed the 52-week upacicalcet treatment. Upacicalcet achieved the target serum iPTH level (60–240 pg/mL) in 94.2% of patients at 52 weeks. Moreover, upacicalcet decreased bone metabolism markers, intact fibroblast growth factor-23 levels, and parathyroid gland volume. Upacicalcet reduced corrected calcium-phosphate product levels even in patients with mild SHPT, i.e., serum iPTH level ≤300 pg/mL. Upacicalcet caused neither symptomatic hypocalcemia nor cCa levels <7.5 mg/dL despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Gastrointestinal symptoms leading to upacicalcet dose reduction were not occurred. In conclusion, upacicalcet stably reduced the serum iPTH levels in HD patients with mild-to-severe SHPT, with few safety concerns. Serum cCa and P levels were well controlled, with a low incidence of hypocalcemia. Upacicalcet is a novel calcimimetic that may provide safe and appropriate long-term treatment of SHPT.

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.

Influence of treatment to remove oral inflammation foci on the systemic malnutrition and inflammation markers of dialysis patients: A series of cases

Background and objectives: Studies report a more precarious oral health status, with a higher prevalence of periodontal disease, in hemodialysis patients. Also, oral inflammation foci, mainly periodontal disease, are related to systemic inflammation and malnutrition which have a negative impact on morbidity and mortality in these patients. The aim of this study is to observe the influence of dental on the general status of these patients. Material and Methods: The study is a series of cases and was conducted in two phases: data collection and treatment phase and monitoring phase. Dental treatment was performed on 13 patients, with ages between 43-69 years of age, diagnosed with moderate or severe periodontal disease. Oral status parameters (plaque and gingival bleeding index, pocket depth, attachment level, DMFT and CPITN index) and general parameters (C-reactive protein, albumin, hemoglobin, calcium phosphate product, calcium and phosphate levels, erythropoietic-stimulating agents) were registered and monitored. Conventional periodontal treatment, dental extractions, endodontic treatments were performed. Results: Oral assessment showed a statistically significant improvement of oral parameters, at both 1 month and 3 months post-treatment. Mean values for albumin, C-reactive protein, hemoglobin, calcium phosphate product and calcium levels had a slight improvement, but the difference was not statistically significant. Conclusion: The oral status, characterized by the measured periodontal parameters, improved visibly and statistically significant after the dental treatment. The parameters of the general status did not change significantly following the intervention.

Impact of Calcium Phosphate Product on Acute Kidney Injury and Mortality: A Retrospective Cohort Study.

This study aims to assess the association between admission-corrected serum calcium phosphate (CaPO4) levels and the risks of in-hospital acute kidney injury (AKI) and mortality, hypothesizing a dose-dependent relationship between serum CaPO4 concentrations and the likelihood of developing AKI. This large retrospective cohort study analyzed hospitalized adult patients who had serum calcium, phosphate, and albumin levels measured within 24 hours of admission between January 2014 and December 2018. Piecewise regression was employed to identify the optimal CaPO4 cutoff values for predicting in-hospital AKI and mortality. Subsequently, the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the risks of in-hospital AKI and mortality associated with these cutoff values. A total of 2,116 patients were included in the study. The incidence rates of AKI for patients with CaPO4 levels ≤27 and >27 mg2/dL2 were 9.6% and 10.9%, respectively. The bilinear association pattern revealed the lowest risk of AKI at a CaPO4 level of 27 mg2/dL2. Piecewise regression analysis showed that each 1 mg2/dL2 increase in CaPO4 level above the 27 mg2/dL2 cutoff was associated with increased risks of in-hospital AKI and mortality, with OR of 1.048 (95% CI: 1.030-1.065) and 1.048 (95% CI: 1.032-1.065), respectively. Our findings indicate a critical relationship between elevated serum CaPO4 levels and increased risks of in-hospital AKI and mortality, with a notable cutoff at CaPO4 >27 mg2/dL2.

Synthesis and Characterization of Calcium Phosphate Using Two Stages of Process

Calcium phosphate, a naturally occurring biomaterial found in human and animal bones and teeth, possesses desirable properties such as strength, biocompatibility, and the ability to stimulate tissue growth. This study investigates the synthesis of calcium phosphate through a precipitation method without calcination. The process involves dissolving raw materials in phosphoric acid, followed by precipitation using KOH as the precipitating agent. The resulting precipitate was then calcined for 3 hours. The calcium phosphate product was characterized using XRF, XRD, and SEM-EDX techniques. The results indicate a Ca-P molar ratio ranging from 1.855 to 2.302, with the predominant phase identified as β-calcium pyrophosphate. SEM analysis reveals a plate-like morphology with agglomerated particles ranging in size from 888 nm to 7.79 μm. The synthesized calcium phosphate holds potential for various biomedical applications due to its unique properties and composition.

Correlation of serum fibroblast growth factor-23 levels and calcium phosphate products levels in chronic kidney disease; sub analysis of chronic kidney disease-mineral and bone disorder study

&lt;em data-sider-select-id="0e59b1fc-fce5-41b4-b987-316daa778de4"&gt;Introduction: The body produces fibroblast growth factor-23 (FGF-23) to maintain normal phosphate levels when hyperphosphatemia occurs. Production of FGF-23 indirectly causes hypocalcemia. Phosphate and calcium disturbances also occur in chronic kidney disease (CKD), therefore this adaptation mechanism applies. This situation; however, only manifests in the early stages of CKD; if the estimated glomerular filtration rate (eGFR) is less than 30% of normal. This adaptation is no longer adequate and levels of calcium-phosphate (Ca×P) products and FGF-23 still rise. &lt;em data-sider-select-id="f0dc3bf1-1598-419e-9de6-fe837eadc8e6"&gt;Objectives: In this study, the correlation between both the serum levels of FGF-23 and Ca×P products in CKD was analyzed. &lt;em data-sider-select-id="a367eeb1-7c32-4bf0-98ef-e6ae52522dc7"&gt;Patients and Methods: A cross-sectional study including 78 subjects with CKD stages 3 to 5 dialysis was conducted. Serum FGF-23 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method and Ca×P product levels were calculated using the formula calcium (mg/ dL) × phosphate (mg/dL). The Kolmogorov-Smirnov test and Spearman’s test were conducted in the statistical study. If the P value is less than 0.05, the statistical findings are significant. &lt;em data-sider-select-id="e286c166-6c09-432e-b832-c902b1a13b81"&gt;Results: Serum FGF-23 levels and Ca×P product levels were shown to be significantly correlated. This analysis of the two correlations was independent of age and diabetes mellitus (DM). Based on stages of CKD, serum FGF-23 levels and Ca×P product levels were discovered to be significantly correlated only at stage 5 of non-dialysis. &lt;em data-sider-select-id="9b3534d4-deaa-4ccf-8b82-745bb5380661"&gt;Conclusion: Increasing serum FGF-23 levels were correlated with increased Ca×P product levels, particularly in CKD stage 5 non-dialysis subjects. This correlation was independent of age and DM.

12. Correlation between Calcium Phosphate Product and Visit-to-Visit Blood Pressure Variability in Patients with Chronic Hemodialysis

12. Correlation between Calcium Phosphate Product and Visit-to-Visit Blood Pressure Variability in Patients with Chronic Hemodialysis

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

Calcination-based direct extraction of hydroxyapatite from bovine bone waste

ABSTRACT The main chemical components of waste cow bones are apatite minerals, especially those containing calcium and phosphorus. This study investigated whether this bone could produce extracted hydroxyapatite through calcining at 900° C for different holding times (1–6 h). An average mass loss of 45% occurred in this experiment during the preparation of bone powders, which involved crushing and further calcining at this temperature. The quantitative XRD analysis showed that 99.97 wt.% hydroxyapatite and over 0.3 wt.% calcite were present in the raw and as-calcined bone powders, with trace amounts of CaFe3O5 (calcium ferrite) phases appearing in the calcined product. Depending on the holding calcining times, SEM images of the calcined bovine powders revealed aggregate sizes ranging from 0.5–3 µm and crystallite (grain) sizes ranging from 70 to 340 nm in all calcium-phosphate powder products. Following EDX analysis of all sample surfaces, possible calcium-deficient hydroxyapatite instead of hydroxyapatite formed, as evidenced by the calcined product's Ca/P ratio exceeding 1.67. Additionally, calcining cow bones for 5–6 h at 900° C yielded a high-purity nano-crystalline hydroxyapatite powder precursor in biomedical applications.

Carotid Intima-Media Thickness in Children with Chronic Kidney Disease as an Early Predictor of Cardiovascular Diseases

Aim: Cardiovascular problems are very common in children with chronic kidney disease (CKD). To examine early cardiovascular risk factors, notably carotid intima-media thickness (CIMT) and pulse wave velocity (PWV). Material and Method: Case-control study was conducted in the Department of Pediatric Nephrology Sindh Institute of Urology and Transplantation Karachi from 1stFebruary 2023 to 31st July 2023. Forty two children were enrolled. CIMT and PWV were measured using ultrasonography and pulse wave analysis respectively. The following clinical parameters were also assessed: blood pressure, age, gender, etiology, duration of chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), serum albumin, calcium-phosphate product, and intact parathyroid hormone (PTH), and vitamin D levels. Results: The average age was 10.2±3.6 years, with a higher proportion of boys in the cases group (69% versus 47.6%, p-value 0.04). Most patients had normal blood pressure (78.6%), and congenital anomalies were the most common CKD etiology (57.1%). Median eGFR was 30.5 ml/min/1.73 m2, with stages 3 and 4 CKD most prevalent. Serum albumin was normal (mean 4.45±0.68), but some cases had a high calcium-phosphate product (7%) and low vitamin D levels (52%). CIMT and PWV did not differ significantly between cases and controls. Echocardiography revealed mild cardiac abnormalities in some cases. Practical implication: Some patients showed minor left ventricular expansion, while others had mildly depressed GLS and decreased LVEF. Further research should focus on longitudinal studies and explore new biomarkers for early cardiovascular risk detection. Conclusion: The various clinical characteristics such as blood pressure, mineral and bone diseases, and cardiac abnormalities are common in children with chronic kidney diseases. There were no significant changes in carotid intima-media thickness and pulse wave velocity between the cases and controls. Keywords: Chronic kidney disease, Carotid intima-media thickness, Cardiovascular disease, Pulse wave velocity

Renal Dysfunction in Primary Hyperparathyroidism is associated with nephrolithiasis, elevated serum calcium-phosphate product and parathormone levels.

Baseline renal dysfunction predicts mortality in primary hyperparathyroidism (PHPT). However, it remains controversial whether renal insufficiency in PHPT is due to disease severity alone or other risk factors. This study aimed to explore the association of clinico-biochemical variables with renal dysfunction [estimated glomerular filtration rate (eGFR) < 60 ml/min/m2] in PHPT. A total of 112 patients of PHPT were selected and divided into following subgroups: renal dysfunction (n = 28) and normal renal function (n = 84). Demographic characteristics, traditional risk factors, phenotypes of PHPT based on target organ involvement, and biochemical parameters were compared between these subgroups. Patient subgroups of PHPT with and without renal dysfunction had similar age, frequency of diabetes, and hypertension. Renal dysfunction was more prevalent in males (p < 0.05). Compared to normal renal function subgroup, individuals with renal dysfunction had higher serum levels of calcium, phosphate, alkaline phosphatase, intact parathormone (all p < 0.05), while having lower hemoglobin levels (p < 0.05) and higher nephrolithiasis rates (p < 0.05). Multiple regression analysis revealed that nephrolithiasis, serum calcium-phosphorous product (CaxP), parathormone levels were positively associated with baseline renal dysfunction (all p < 0.01). A baseline PTH > 456 pg/mL and CaxP > 30.0 mg2/dl2 could discriminate renal dysfunction from normal renal function with sensitivity and specificity of 75% and 74.5% and 92.6% and 74.4%, respectively. Renal dysfunction was associated with presence of nephrolithiasis, elevated serum CaxP and PTH levels in our cohort with predominantly symptomatic PHPT, indicating an association with the underlying disease itself. Serum CaxP may additionally be appraised during risk assessment in PHPT.

Extended Treatment With Recombinant Human Parathyroid Hormone (1-84) in Adult Patients With Chronic Hypoparathyroidism

ObjectiveRecombinant human parathyroid hormone (1-84) (rhPTH[1-84]) is efficacious in patients with hypoparathyroidism but additional data supporting its prolonged use are needed. We evaluated whether efficacy, safety, and tolerability are maintained during long-term rhPTH(1-84) treatment of patients with chronic hypoparathyroidism. MethodsThis was a phase 4, single-center, open-label, single-arm, 3-year extension (NCT02910466) of the phase 3 Hypo Extended (HEXT) study (NCT01199614). Patients self-administered rhPTH(1-84) once daily by subcutaneous injection, with doses individualized based on clinical parameters. Albumin-adjusted serum calcium levels (primary outcome measure), other disease biomarkers, health-related quality of life, and safety of rhPTH(1-84) were assessed using descriptive statistics. ResultsAll patients (n = 39) had been exposed to rhPTH(1-84) (mean exposure [SD] 8.5 [3.5] years) before the start of the study, resulting in a mean exposure of 10.8 years including the present study. Mean patient age was 51.9 years, 79.5% were female, and 97.4% were White. Mean albumin-adjusted serum calcium concentrations were within the target range, and mean serum phosphate, serum calcium-phosphate product, and 24-hour urinary calcium excretion levels were within reference ranges at end of treatment. Mean doses of supplemental calcium and active vitamin D were maintained throughout the study. Bone turnover marker levels were maintained from baseline to end of treatment. No clinically relevant changes in bone mineral density were observed. Patient-reported health-related quality-of-life scores were generally maintained throughout the study. Four adverse events were considered treatment related and no new safety signals were identified. ConclusionThe effects of rhPTH(1-84) on biochemical, skeletal, and health-related quality-of-life parameters did not wane with extended use.

Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore.

Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD).The treatment for SHPT includessynthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore. Methods This study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT.The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals. Results A total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications. Conclusion Etelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

The effect of intradialytic exercise on calcium, phosphorus and parathyroid hormone: a randomized controlled trial

BackgroundPatients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which results in high mortality rate in these patients. This study aimed to evaluate the effect of intradialytic exercise on regulation of these abnormalities in patients receiving chronic hemodialysis (HD).MethodsIn this randomized controlled trial conducted in an HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 min) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcomes were serum calcium, serum phosphorous and parathyroid hormone levels. Secondary outcomes were serum alkaline phosphatase and calcium-phosphorous product.ResultsThe study included 44 participants randomized to intervention (n = 22) or control (n = 22). During the 6-month intervention period, significant between-group changes were observed in all primary and secondary outcomes between the intervention and control groups. Statistical analyses reveal a significant increase in serum calcium (P < 0.05) as well as a significant decrease in serum phosphorous, parathyroid hormone, alkaline phosphatase and calcium-phosphorous product (P < 0.05).ConclusionIntradialytic exercise performed for at least 60 min during thrice weekly dialysis sessions improves bone mineral metabolism in adult patients receiving HD. Further studies should focus on observing and comparing the effect of different types of exercise on bone mineral disorders and all-cause mortality in HD patients.Trial registrationClinicalTrials.gov Identifier: NCT04916743, Registered on 08/06/2021. Registered trial name: The Effect of Intradialytic Exercise on Calcium, Phosphorous and Parathyroid Hormone: A Randomized Controlled Trial.

Study of Hemoglobin and Calcium Phosphorus Product in Patients with Chronic Kidney Disease

Introduction: Kidneys play a vital role in the metabolism of minerals such as calcium and phosphorous. Moreover, kidney is involved in the production of erythropoietin hormone.The bone marrow suppression may occur in Chronic Kidney Disease (CKD) patients. Reduced hemoglobin and increased calcium phosphorous product concentration is also common in CKD patients.The current study is aimed to find out the impact of CKD in calcium phosphorous product and hemoglobin level in Nepalese population.&#x0D; Materials And Methods: One hundred consecutive diagnosed cases of CKDpatients were enrolled retrospectively for the study. Calcium, phosphorous, urea, creatinine and other biochemical parameters were measured in fully automated biochemistry analyzer and hemoglobin was measured using hematology analyzer (Beckman Coulter DxH500 Automated Hematology analyzer).&#x0D; Results: The current study revealed the hemoglobin and calcium phosphorous product in CKD patients.The Calcium Phosphorous Product (CaP) of 69 subjects were having less than &lt;40mg2/dL2 and remaining 31 were having ≥ 40mg2/dL2. The negative correlation of calcium phosphorous product was seen with calcium (r= -0.478, p-value = 0.000) and sodium (r=-0.309, p-value=0.002) whereas positive correlation of calcium phosphorous product was seen with urea (r= 0.559, p-value=0.000) andCreatinine (r=0.353, p-value = 0.000). The creatinine was negatively correlated with the hemoglobin concentration (r= -0.320, p-value = 0.001).&#x0D; Conclusion: Calcium phosphate product can be fluctuated in chronic kidney disease patients along with the decrement of hemoglobin concentration. The serum calcium phosphorous product measurement can assist to rule out the severity of chronic kidney disease.

Protective nature of cerium-based oxides coating against Mg corrosion in Hanks’ balanced salt solution

The cerium-based coatings have attracted increasing attention for modifying Mg surface in biomedical applications due to their corrosion protectiveness and potential biological effects. However, their anti-corrosion mechanisms have not been fully understood. In this work, the corrosion resistance of anodic electrodeposited cerium-based oxides coating on Mg alloy was investigated in Hanks’ balanced salt solution. The obtained results demonstrate that the strengthened precipitation of protective calcium phosphate products on this coating results in its enhanced anti-corrosion nature. These findings enrich the understanding on anti-corrosion mechanisms of the cerium-based coating and point out its prospect on Mg alloys for bone implants.