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Target values for 25-hydroxy vitamin D and 1,25(OH) 2 D 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) 2 D. Cohort B, including 47,778 subjects, was used to investigate the connection between 25(OH)D/1,25(OH) 2 D 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) 2 D. Minimal CRP and WBC counts were observed at 1,25(OH) 2 D 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) 2 D 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) 2 D 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.

Objective: Ectopic calcification such as vascular calcification, involves the formation of calciprotein particle (CPP), that is, colloidal particle of calcium phosphate bound to serum protein. In this study, a novel parameter for CPP formation was introduced, thereby the effect of FYB-931, a bisphosphonate compound was evaluated., Methods: CPP formation in rat serum was assessed by the area under the curve (AUC) of the change in absorbance over time, and the commonly used T50, as indices. In vivo, the rats were treated with vitamin D3 to induce vascular calcification and then intravenously administered FYB-931 or etidronate thrice weekly for 2 weeks., Key Findings: In vitro, FYB-931 was the most potent inhibitor of CPP formation and it also inhibited the maximum response of CPP formation at higher concentrations. The AUC of the change in absorbance provided obvious dose-dependency, while T50 did not. FYB-931 dose-dependently prevented aortic calcification in vivo as well as CPP formation ex vivo more potently than etidronate. AUC showed a stronger correlation with the degree of aortic calcification than T50., Conclusions: The AUC in CPP formation can be an alternative parameter that reflects calcification. Based on the findings, FYB-931 has potential as an anti-calcifying agent., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Phosphate toxicity is a major threat to cardiovascular health in chronic kidney disease. It is associated with oxidative stress, inflammation and the accumulation of calcium phosphate commonly known as calcification in soft tissues leading to functional disorders of blood vessels. An improved calcification propensity test for the assessment of phosphate toxicity was developed, which measures the velocity of calcium phosphate mineralization from colloidal precursors in vitro. This so called T50 test measures the transformation from a primary into a secondary form of nanosized colloidal plasma protein-calcium phosphate particles known as calciprotein particles. The T50 test in its previous form required a temperature controlled nephelometer and several hours of continuous measurement, which precluded rapid bed side testing. We miniaturized the test using microfluidic polymer chips produced by ultrasonic hot embossing. A cartridge holder contained a laser diode for illumination, light dependent resistor for detection and a Peltier element for thermo control. Increasing the assay temperature from 37°C to 75°C reduced the T50 test time 36-fold from 381 ± 10 min at 37°C to 10.5 ± 0.3 min at 75°C. Incorporating sputtered micro mirrors into the chip design increased the effective light path length, and improved signal-to-noise ratio 9-fold. The speed and reproducibility of the T50 chip-based assay run at 75°C suggest that it may be suitable for rapid measurements, preferably in-line in a dialyser or in a portable microfluidic analytic device with the chip inserted as a disposable cartridge., Competing Interests: The authors have read the journal's policy and have the following conflicts: AP and WJD are co-founders and share holders of Calciscon AG, a start-up company based at Nidau, Switzerland. AP is an employee of Calciscon AG, who provided support in the form of salaries for author AP. The commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aim: Disturbances in mineral metabolism markers are common in patients with chronic kidney disease but there is no consensus on the association between these markers and clinical outcomes. This study investigated associations between mineral metabolism parameters and mortality in Chinese peritoneal dialysis (PD) patients., Methods: This was a single-centre retrospective cohort study. Incident PD patients between 1 January 2006 and 31 December 2013 with baseline phosphate, albumin-corrected calcium, and calcium-phosphate product data were enrolled. Associations between these parameters and all-cause and cardiovascular mortality were assessed using multivariable-adjusted Cox models., Results: Of 1662 patients (mean age: 47.4 ± 15.3 years), 59.3% were male and 23.8% had diabetes. Over a median 38.1 month (interquartile range: 21.3-59.7 months) follow-up period, 382 (23.0%) patients died. After adjusting for confounders, the higher serum phosphate level (>1.78 mmol/L) and calcium-phosphate product level (≥4.4 mmol 2 /L 2 ) were significantly associated with an increased risk for all-cause mortality (hazards ratio (HR) = 1.818, 95% CI = 1.379-2.396 and HR = 1.735, 95% CI = 1.261-2.386) and cardiovascular mortality (HR = 2.069, 95% CI = 1.428-2.998 and HR = 2.175, 95% CI = 1.450-3.262), respectively. While each 1 mmol/L higher baseline albumin-corrected calcium level was associated with an 14.3% (95% CI = 0.749-0.981) lower risk for all-cause mortality after adjusting for potential confounders., Conclusion: Abnormalities in mineral metabolism markers, particularly higher serum phosphate and calcium-phosphate product levels, at the commencement of PD were independently associated with increased all-cause and cardiovascular mortality in this cohort of PD patients., (© 2018 Asian Pacific Society of Nephrology.)

BACKGROUND Increased serum levels of basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) are found in patients on dialysis, following trauma, and are associated with connective tissue diseases (CTDs), including dermatomyositis, scleroderma, and systemic lupus erythematosus (SLE). The shoulder is the joint most commonly associated with BCP crystal periarthritis. A report is presented of a case of BCP crystal periarthritis involving the distal interphalangeal (DIP) joints in a patient with SLE. CASE REPORT A 34-year-old woman with SLE presented with destructive arthritis of the DIP joints that developed during a two-year period, despite immunosuppressive therapy. Aspiration of synovial fluid from a DIP joint showed a lack of inflammatory cells, but the fluid was positive for the presence of crystals on alizarin red S histochemical staining. CONCLUSIONS A case of BCP crystal periarthritis is reported in a patient with SLE with chronic joint symptoms that were unresponsive to immunosuppressive therapy. This case has shown that chronic joint symptoms that are unresponsive to immunosuppressive therapy may be due to causes other than connective tissue disease (CTD) and that imaging studies and diagnostic workup that includes synovial fluid examination may support the diagnosis of BCP crystal periarthritis.

Objectives: There is an increased calcium phosphate product level causing the formation of calcification in the arterial wall and thus decreased quality of fistula in patients with chronic renal failure. The purpose of our study is to verify the relationship between arteriovenous fistula re-operation and high calcium phosphate product level., Methods: Seventy-nine consecutive patients with chronic renal failure between April 2016 and February 2018 were included in the study. Patients having calcium phosphate product level ≥50 mg 2 /dl 2 were defined as group 1, whereas those having <50 mg 2 /dl 2 were defined as group 2. Primary outcome of interest was the need for re-operation during the follow-up and to determine the risk factors for re-operation. To determine independent predictors for re-operation, multivariate logistic regression model was used., Results: The rates of redo and tredo operation were significantly higher in group 1 compared to group 2 ( p = 0.01 and 0.04). In multivariate analysis, phosphate (OR: 1.84, 95% CI: 1.00-3.40, p = 0.05) and triglyceride (OR: 1.01, 95% CI: 1.00-1.02, p = 0.04) levels for redo operation and calcium phosphate product level (OR: 1.11, 95% CI: 1.01-1.22, p = 0.03) for tredo operation were found to be independent predictors., Conclusions: High calcium phosphate product level leads to increased risk of arteriovenous fistula re-operation by causing arterial stiffness in this patient group. Additionally, these re-operations place additional burden on morbidity and cost efficacy. Thus, we recommend keeping the calcium phosphate product level at the optimal level in these patients to avoid both the risk of arteriovenous fistula re-operation and the other cardiovascular problems.

The total calcium (tCa) in blood serum comprises free Ca 2+ ions (fCa), protein-bound calcium (prCa), and complexed calcium by small anions (cCa). The cCa fraction, in addition to fCa, has been indicated to have some physiological activity. However, there is little evidence for the structure of its constituents. Here we report an ex vivo detection of the cCa constituents by synchrotron X-ray absorption near-edge structure spectroscopy. We collected the data directly on rat blood serum and, by making use of the reference samples, derived a spectrum that exhibits the features of cCa constituents. Among the features are those of the complexes of calcium phosphate and calcium carbonate. The detected complexes in the cCa fraction are mainly Ca(η 2 -HPO 4 )(H 2 O) 4 and Ca(η 1 -HCO 3 )(H 2 O) 5 + , in which HPO 4 2- and HCO 3 - serve as bidentate and unidentate ligands, respectively. The remained H 2 O molecules on the coordination sphere of Ca 2+ enable these complexes to behave partially like aquated Ca 2+ ions in protein-binding. Besides, as the dominant part of prCa, albumin-bound calcium (albCa) exhibits a spectrum that closely resembles that of fCa, indicating weak interactions between the protein carboxyl groups and calcium. The weak-bound cCa and albCa, along with fCa and the relevant anions, compose a local chemical system that could play a role in maintaining the calcium level in blood., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: Serum calcification propensity is a novel functional test that quantifies the functionality of the humeral system of calcification control. Serum calcification propensity is measured by T 50 , the time taken to convert from primary to secondary calciprotein particle in the serum. Lower T 50 represents higher calcification propensity and is associated with higher risk of cardiovascular events and death in patients with ESKD. Increasing magnesium in serum increases T 50 , but so far, no clinical trials have investigated whether increasing serum magnesium increases serum calcification propensity in subjects with ESKD., Design, Setting, Participants, & Measurements: We conducted a single-center, randomized, double-blinded, parallel group, controlled clinical trial, in which we examined the effect of increasing dialysate magnesium from 1.0 to 2.0 mEq/L for 28 days compared with maintaining dialysate magnesium at 1.0 mEq/L on T 50 in subjects undergoing hemodialysis for ESKD. The primary end point was the value of T 50 at the end of the intervention., Results: Fifty-nine subjects were enrolled in the trial, and of these, 57 completed the intervention and were analyzed for the primary outcome. In the standard dialysate magnesium group, T 50 was 233±81 minutes (mean±SD) at baseline (mean of days -7 and 0) and 229±93 minutes at follow-up (mean of days 21 and 28), whereas in the high dialysate magnesium group, T 50 was 247±69 minutes at baseline and 302±66 minutes at follow-up. The difference in T 50 between the two groups at follow-up (primary analysis) was 73 minutes (between-group difference; 95% confidence interval, 30 to 116; P <0.001), and the between-group difference in serum magnesium was 0.88 mg/dl (95% confidence interval, 0.66 to 1.10; P =0.001)., Conclusions: Increasing dialysate magnesium increases T 50 and hence, decreases calcification propensity in subjects undergoing maintenance hemodialysis., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018&#95;08&#95;21&#95;CJASNPodcast&#95;18&#95;9&#95;B.mp3., (Copyright © 2018 by the American Society of Nephrology.)

Context: Some patients with primary hyperparathyroidism (PHPT) develop renal calcifications. Investigation of urinary and nonurinary risk factors are essential., Objective: We aimed to study the prevalence and potential biochemical predictors of renal calcifications., Design: Nested case-control study., Setting: University hospital., Participants: We identified 792 patients with PHPT from 2005 to 2015. We used biochemical data to validate the diagnosis of PHPT., Main Outcome Measures: The prevalence of renal calcifications defined as nephrolithiasis or nephrocalcinosis assessed by a routine CT scan at the time of diagnosis., Results: A total of 792 patients with PHPT were identified among whom 617 patients (78%) had a CT scan preformed. We found a prevalence of renal calcifications of 23%, equally frequent between sexes. A total of 76 patients (12%) had nephrolithiasis and 75 patients (12%) had nephrocalcinosis where 7 patients (1%) had both nephrolithiasis and nephrocalcinosis. Compared with patients without renal calcifications, patients with renal calcifications had significantly higher levels of ionized calcium, parathyroid hormone, and 24-hour calcium excretion (Pall < 0.01). Patients with nephrocalcinosis had higher plasma levels of phosphate and a higher calcium-phosphate product compared with patients with nephrolithiasis (Pall < 0.05). Impaired renal function (estimated glomerular filtration rate <60 mL/min) was observed in 12% of patients. However, no differences in renal function were observed between those with and without renal calcifications., Conclusion: Renal calcifications are frequent in patients with PHPT and are associated with the severity of the disease. Impaired renal function is also common in PHPT, but renal function was not associated with renal calcifications.

Background: Micro-crystals of calcium phosphate have been detected on the aortic valve of patients with aortic stenosis using scanning electron microscopy. It is not known whether crystalisation is specific to heart valve tissue or a general blood-derived process., Methods: To this end we modified the method to determine whether calcium phosphate micro-crystals were present in the blood of patients with aortic stenosis. The method was first validated by adding synthetic calcium phosphate hydroxyapatite micro-crystals to healthy volunteer blood samples and determining the lower limit of detection. Then the method was used to examine the blood of 63 patients with echocardiographically confirmed aortic stenosis and 69 unaffected controls undergoing echocardiography for other reasons. Serum calcium and phosphate were measured and the calcium phosphate product compared in cases and controls., Results: In the validation study, synthetic hydroxyapatite micro-crystals were identified down to a lower concentration limit of 0.008mg/mL. In the experimental study no particles were identified in any patient, with or without aortic stenosis, even though serum calcium phosphate was higher in cases compared with controls 2.6mmol/L (2.58-2.77) versus 2.47mmol/L (2.36-2.57), p = 0.005 for the difference., Conclusion: The results of our study confirm a positive association between serum calcium phosphate and aortic stenosis, but indicate that the calcium phosphate particles found in valve tissue do not precipitate freely in the blood., Competing Interests: The authors would like to declare the following patents/patent applications associated with this research: DSW is the inventor on a Queen Mary University of London patent application for the treatment of aortic stenosis (PCT/GB2018/051556). The authors have declared that no other competing interests exist.

Background: Vitamin D (VD) insufficiency or deficiency is a frequent comorbidity in Chinese women with postmenopausal osteoporosis (PMO). The present study aimed to investigate 25-hydroxyvitamin D [25(OH) D] improvement and calcium-phosphate metabolism in Chinese PMO patients treated with 70 mg of alendronate sodium and 5600 IU of vitamin D 3 (ALN/D5600)., Methods: Chinese PMO women (n = 219) were treated with 12-month ALN/D5600 (n = 111) or calcitriol (n = 108). Changes in 25(OH) D at month 12 were post hoc analyzed by the baseline 25 (OH) D status using the longitudinal analysis. The main safety outcome measures included serum calcium and phosphate and 24-h urine calcium, and the repeated measures mixed model was used to assess the frequencies of the calcium-phosphate metabolic disorders., Results: Absolute change in mean serum 25(OH) D level was the greatest in VD-deficient patients and least in VD-sufficient patients at months six and 12 (both, P < 0.01). Serum calcium level remained significantly lower in the ALN/D5600 treatment group than in the calcitriol treatment group throughout the 12 months. Mean 24-h urine calcium slightly increased in the ALN/D5600 treatment group and significantly increased in the calcitriol treatment group (+ 1.1 and + 0.9 mmol/L at months six and 12; both, P < 0.05). Calcitriol treatment was associated with more frequent hypercalciuria at month six (9.4% vs. 18.5%, P = 0.05), but not at month 12 (12.3% vs. 13.0%)., Conclusion: Baseline VD status predicted 25(OH) D improvement in PMO patients on 12-month ALN/D5600 treatment. The daily use of 0.25 μg of calcitriol was associated with more frequent hypercalciuria at month six, compared to ALN/5600 treatment, necessitating the safety re-evaluation of calcitriol at a higher dosage.

Disturbances in mineral metabolism, namely chronic kidney disease-metabolic bone disease, became more profound with impairment of renal function. The aim of the study was to assess how often calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) were measured in kidney transplant recipients relative to hemodialyzed patients. In addition, prevalence of hypercalcemia defined as calcium concentration over 10.5 mg/dL was assessed., Patients and Methods: We studied 200 kidney allograft recipients and 100 hemodialyzed patients. Calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D, and PTH were obtained from outpatient charts., Results: All the studied parameters were available in 100% of the hemodialyzed patients. In kidney allograft recipients, calcium and phosphate levels were available in 80%, alkaline phosphatase activity was available in 40%, PTH was available in less than 10%, and vitamin D was available in 1%. Hypercalcemia was present in 10% of hemodialyzed patients and in 5% of kidney allograft recipients. Vitamin D analogue was administered to 98% of hemodialyzed patients, whereas vitamin D was administered to 28% of kidney allograft recipients, particularly those with impaired kidney function. In conclusion, calcium and phosphate are seldom assessed on an outpatient basis in kidney allograft recipients, making the diagnosis and treatment of secondary hyperparathyroidism in this population difficult. Care of kidney transplant recipients could be substantially improved, particularly in regard to chronic kidney disease-metabolic bone disease, when regular check-ups for calcium-phosphate balance are implemented and proper treatment could be introduced to prevent further chronic kidney disease-metabolic bone disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Backround: Secondary hyperparathyroidism (SHPT) is a manifestation of chronic kidney disease mineral bone disorder (CKD-MBD). SHPT is common in patients with chronic kidney disease (CKD) and is associated with significant morbidity and mortality., Methods: A cross- sectional descriptive study involving 230 patients with CKD., Results: The mean age of the study population was 44.17±15.24 years. The median intact parathyroid hormone and alkaline phosphatase levels were 96pg/ml (range 4-953pg/ml) and 88 iu/l (range 10-800 iu/l) respectively. The mean (with standard deviation) calcium, serum phosphate, calcium phosphate product and haemoglobin levels were 2.22±0.29mmol/l, 1.8±0.62mmol/l, 3.94±1.42mmol 2 /l 2 and 9.90±1.87g/dl respectively. Majority of patients had advanced CKD with 70.3% of patients in stage G5. The prevalence rates of SHPT, hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase and elevated calcium phosphate product were 55.2%, 34.8%, 66.1%, 42.2% and 25.2% respectively.Univariate analysis revealed that SHPT was associated with hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase, proteinuria, anaemia, hypertension, left ventricular hypertrophy and stage of kidney disease; being worse with advancing kidney disease. Independently associated with SHPT were hypocalcaemia (OR=4.84), hyperphosphataemia (OR=3.06), and elevated alkaline phosphatase (OR=2.04)., Conclusion: The prevalence of SHPT in CKD is high, occurs early and is independently associated with hypocalcaemia, hyperphosphataemia and elevated alkaline phosphatase. The prevalence of SHPT also increases with worsening renal function.

Aim: Calciprotein particles (CPPs), colloidal protein-mineral nanoparticles composed of solid-phase calcium phosphate and serum protein fetuin-A found in blood, are emerging as a novel component of chronic kidney disease-mineral and bone disorder (CKD-MBD). The relationship of CPPs with factors known to underlie the CKD-MBD pathophysiology is not well known.The aim of this study is to examine daily variations in CPPs as well as their association with mineral metabolism parameters in normal individuals and early-stage CKD patients., Methods: Twenty subjects (10 healthy adults, 10 diabetic patients) were enrolled. Serum CPP Fetuin-A was measured and analyzed in relation to clinical parameters., Results: Estimated glomerular filtration rates (eGFR) were 103 ± 11 and 75 ± 24 mL/min per 1.73 m 2 in healthy adults and diabetic patients, respectively. Serum CPP Fetuin-A (g/L) were elevated at postprandial 2 h in diabetic patients. Furthermore, serum CPP Fetuin-A were inversely correlated with eGFR and serum 1,25-dihydroxyvitamin D 3 and magnesium levels and were positively correlated with serum fibroblast growth factor-23., Conclusions: These findings indicated that serum CPP Fetuin-A were affected by food intake and may contribute to the pathophysiology of mineral metabolism in subjects with normal and moderately impaired renal function., (© 2017 Asian Pacific Society of Nephrology.)

We developed a mathematical model of calcium (Ca) and phosphate (PO 4 ) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO 4 balance. The model represents the exchanges of Ca and PO 4 between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO 4 -fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D 3 , fibroblast growth factor 23, and Ca 2+ -sensing receptors. Our results suggest that the Ca and PO 4 homeostatic systems are robust enough to handle small perturbations in the production rate of either PTH or vitamin D 3 The model predicts that large perturbations in PTH or vitamin D 3 synthesis have a greater impact on the plasma concentration of Ca 2+ ([Ca 2+ ] p ) than on that of PO 4 ([PO 4 ] p ); due to negative feedback loops, [PO 4 ] p does not consistently increase when the production rate of PTH or vitamin D 3 is decreased. Our results also suggest that, following a large PO 4 infusion, the rapidly exchangeable pool in bone acts as a fast, transient storage PO 4 compartment (on the order of minutes), whereas the intracellular pool is able to store greater amounts of PO 4 over several hours. Moreover, a large PO 4 infusion rapidly lowers [Ca 2+ ] p owing to the formation of CaPO 4 complexes. A large Ca infusion, however, has a small impact on [PO 4 ] p , since a significant fraction of Ca binds to albumin. This mathematical model is the first to include all major regulatory factors of Ca and PO 4 homeostasis., (Copyright © 2017 the American Physiological Society.)

Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of biomarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.

Calciprotein particles, nanoscale aggregates of insoluble mineral and binding proteins, have emerged as potential mediators of phosphate toxicity in patients with Chronic Kidney Disease. Although existing immunochemical methods for their detection have provided compelling data, these approaches are indirect, lack specificity and are subject to a number of other technical and theoretical shortcomings. Here we have developed a rapid homogeneous fluorescent probe-based flow cytometric method for the detection and quantitation of individual mineral-containing nanoparticles in human and animal serum. This method allows the discrimination of membrane-bound from membrane-free particles and different mineral phases (amorphous vs. crystalline). Critically, the method has been optimised for use on a conventional instrument, without the need for manual hardware adjustments. Using this method, we demonstrate a consistency in findings across studies of Chronic Kidney Disease patients and commonly used uraemic animal models. These studies demonstrate that renal dysfunction is associated with the ripening of calciprotein particles to the crystalline state and reveal bone metabolism and dietary mineral as important modulators of circulating levels. Flow cytometric analysis of calciprotein particles may enhance our understanding of mineral handling in kidney disease and provide a novel indicator of therapeutic efficacy for interventions targeting Chronic Kidney Disease-Mineral Bone Disorder.

Aims: To assess whether circulating 25-hydroxyvitamin D 3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease., Methods: We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained., Results: We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg 2 /dL 2 ) product was positively associated with the presence of carotid plaques (OR adj  = 1.078; 95% CI: 1.017-1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) ( β adj  ± SE = -0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM.

Hyperhomocysteinemia (HHcy) is recognized as a risk factor for cardiovascular disease. However, the prevalence of HHcy and its role in association with target organ damage in patients with chronickidney disease (CKD) are not well understood. This cross-sectional study included 1042 CKD patients who were admitted to our hospital. Patients were divided into two groups: hyperhomocysteinemia and normohomocysteinemia. Multivariable linear regression analyses were used to evaluate the association between plasma homocysteine and renal/cardiovascular parameters. The prevalence of HHcy in patients with CKD was 52.78%, and the prevalence in CKD stage 1, stage 2, stage 3, stage 4 and stage 5 patients was 10.73%, 29.22%, 58.71%, 75.23% and 83.75%, respectively. Patients with HHcy had higher incidences of renal damage, left ventricular hypertrophy, left ventricular diastolic dysfunction and abnormal carotid intima-media thickness compared with patients with normohomocysteinemia ( p < 0.05), while multivariable linear regression analyses showed plasma homocysteine was only associated with the estimated glomerular filtration rate (eGFR). eGFR, uric acid, albumin, gender, hemoglobin and calcium×phosphate were associated with levels of plasma homocysteine in these CKD patients. The prevalence of HHcy in Chinese patients with CKD was high, and serum homocysteine levels were associated with impaired renal function in these patients., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: Knowledge about the variability in the request of calcium-phosphate metabolism laboratory tests in primary care is important to design strategies to improve health system efficiency., Aim: To compare the inter-practice variability in calcium-phosphate metabolism laboratory tests requested by general practitioners from diverse regions across Spain., Material and Methods: One hundred and forty one clinical laboratories were invited to participate in an observational cross-sectional study. They informed the number of serum calcium, phosphate, parathyroid hormone and 25-hydroxyvitamin D requested by general practitioners. Appropriateness indicators were calculated as number of test requests per 1,000 inhabitants and ratio of related tests requests. The differences according to hospital setting, region and type of management were analyzed., Results: We recruited 76 laboratories (17,679,195 inhabitants). General practitioners requested 3,260,894 calcium-phosphate metabolism tests. The rate of request ranged from 2.97 per 1,000 inhabitants for 25-hydroxyvitamin D to 98.89 per 1,000 inhabitants for calcium. The rates of request for calcium, phosphate, parathyroid hormone in some areas were 30, 100 and 340 times higher than in other areas. Parathyroid hormone and 25-hydroxyvitamin D were highly requested in private management areas. There were also differences in phosphate, parathyroid hormone and 25-hydroxyvitamin D requesting between regions across Spain., Conclusions: The high variability observed is difficult to explain by differences in patient case mix between regions. Depending on the area, calcium could be under requested to detect primary hyperparathyroidism.

Introduction: Fractures of the proximal femur are a significant cause of mortality and morbidity in the elderly population. Yet predictive marker of unfavourable prognosis are still lacking. Calcium phosphate product is a marker of osteo-renal dysregulation. This study investigated the role of serum calcium phosphate product (SCPP) levels as a prognostic parameter for outcome in those patients., Patients and Methods: A total of 3577 consecutive patients with diagnosed fractures of the proximal femur were included in our study (72.5% females). SCPP was divided into tertiles: <1.92mmol(2)/l(2), 1.93-2.38mmol(2)/l(2) and >2.39mmol(2)/l(2). Data collection was performed prospectively and statistical evaluation was performed retrospectively., Results: Mean follow up in our study group was 11.0±0.3 months. The mean age of our study group was 79.0 years (SEM ±14 years). To facilitate analysis, patients were divided in two groups: ≤84 years (64.4%) and ≥85 years (35.6%), and mortality <12 months was 12.4% (n=445). In our study population higher SCPP levels ad admission were associated with a markedly elevated mortality. In a multivariate logistic regression model adjusted for age and sex, plasma creatinine and haemoglobin at admission caused a 1.3 (CI: 1.01-1.6) for SCPP 1.93-2.38mmol(2)/l(2), and a 1.6 (CI: 1.2-2.0) for SPP >2.39mmol(2)/l(2) fold increase in overall mortality compared to patients with baseline SCPP levels (<1.92mmol(2)/l(2)) as reference category., Conclusion: Those findings in our study population with 3577 patients over a period of 20 years proved to be, that serum Ca levels may be a good predictor for mortality in patients with fracture of the proximal femur. Further studies are required to evaluate whether these high risk patients might benefit from specific therapeutic measurements. This prognostic factor may help to increase the outcome of elderly patients with a fracture of the proximal femur., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken., Results: Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001)., Conclusions: In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.

Background: Dialysis patients received intravenous iron to treat anemia and had high prevalence of peripheral artery disease (PAD). We hypothesized that high iron status might associate with the progression of PAD among hemodialysis patients. Therefore, we evaluated the relationship between iron status and progression of PAD., Methods: We measured iron status in 74 hemodialysis patients and studied the association with clinical, biochemical, and vascular parameters including progression of PAD measured by ankle-brachial index (ABI) over 3 years., Results: Mean baseline ABI was 1.03 ± 0.18. Mean ABI at 3 years was 0.95 ± 0.20. Mean ∆ABI (change in ABI after 3 years) was -0.08 ± 0.14. Serum ferritin was negatively correlated with baseline ABI (r = -0.232, p = 0.046). After 3 years, ∆ABI was negatively associated with 3-year averaged serum ferritin, phosphorus, and calcium-phosphate product (Ca × P) (r = -0.253, p = 0.029; r = -0.278, p = 0.016; r = -0.288, p = 0.013; respectively). After an adjusted model, 3-year averaged serum ferritin and Ca × P remained the significant determinants of ∆ABI (β = -0.234, p = 0.038; β = -0.271, p = 0.017; respectively). ∆ABI was significantly different between 3-year averaged serum ferritin level ≥600 and <600 ng/mL (p = 0.032)., Conclusions: In hemodialysis patients, high serum ferritin associates with progression of PAD, especially among those with high Ca x P level.

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low-flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start-to-end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca-phosphate (P)-parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. "Severe" secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8-2.1 m(2) ), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca-P-PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start-to-end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in "severe" secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on "low-flow" daily home dialysis, in "severe" secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques., (© 2015 International Society for Hemodialysis.)

We established a rat model of hyperphosphatemia and investigated the systemic effects of high phosphorus (P). Sprague Dawley rats were randomly divided into high (HP), low (LP), and normal (NP) P groups (N = 12 each), which received injections of fructose diphosphate sodium, or were fed self-manufactured low phosphorus or normal diets, respectively. In each group, 4 rats were sacrificed at the first, third, and sixth week to detect the serum (Scr) and urinary creatinine and P, and calcium (Ca) levels. The HP group's serum P and intact parathyroid hormone (iPTH) were significantly higher than those in the other groups at the first, third, and sixth weeks, (P < 0.05); the LP group's serum P was lower than the NP group's at the third week (P < 0.05), while at the sixth week, the serum P and iPTH were lower (P < 0.05). No significant differences were detected for blood Ca+ (P > 0.05). The HP group's Scr increased (P < 0.01), whereas the fractional excretion decreased (P < 0.05) significantly. Thighbone and lumbar spine bone densities differed significantly between groups in the third week (P < 0.05); LP group densities were lower than NP group measures (P < 0.05). Crystallized stones were not observed microscopically following hematoxylin and eosin staining of the kidney. We successfully established a hyperphosphatemia rat model, and high blood P was found to significantly influence renal function and bone density. These results might provide a foundation to study the effects of hyperphosphatemia in rats.

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic dysfunction of mineral and bone metabolism in people with CKD. Recent research shows that phosphate retention plays a significant role in the development of CKD-MBD. Compared with drug therapies, dietary interventions may be simple, inexpensive and feasible for phosphate retention. However, there is little evidence to support these interventions., Objectives: Our objective was to assess the benefits and harms of any dietary intervention for preventing and treating CKD-MBD., Search Methods: We searched Cochrane Kidney and Transplant's Specialised Register to 27 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We also searched the Chinese Biomedicine Database (CBM) (1976 to August 2015), China Knowledge Resource Integrated Database (CNKI) (1979 to August 2015), and VIP (1989 to August 2015)., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs looking at dietary interventions for prevention or treatment of CKD-MBD were eligible for inclusion., Data Collection and Analysis: Two authors independently assessed the eligibility, methodological quality, and extracted data. Continuous outcomes (serum calcium level, serum phosphorus level, calcium × phosphate product, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23) and alkaline phosphatase) were expressed as mean difference (MD) with 95% confidence interval (CI). Dichotomous outcomes (mortality) were expressed as risk ratio (RR) with 95% CI. We used a random-effects model to meta-analyse studies., Main Results: Nine studies were included in this review which analysed 634 participants. Study duration ranged from 4 to 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post haemodialysis supplements and hypolipaemic diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. There was insufficient reporting of design and methodological aspects among the included studies to enable robust assessment of risk of bias.There was limited and low-quality evidence to indicate that calcium-enriched bread increased serum calcium (1 study, 53 participants: MD -0.16 mmol/L, 95% CI -0.51 to -0.31), decreased serum phosphorus (53 participants: MD -0.41 mmol/L, 95% CI -0.51 to -0.31) and decreased the calcium × phosphate product (53 participants: MD -0.62 mmol²/L², 95% CI -0.77 to -0.47).Very low protein intake was not superior to conventional low protein intake in terms of effect on serum phosphorus (2 studies, 41 participants: MD -0.12 mmol/L, 95% CI -0.50 to 0.25), serum calcium (MD 0.00 mmol/L, 95% CI -0.17 to 0.17), or alkaline phosphatase (MD -22.00 U/L, 95% CI -78.25 to 34.25). PTH was significantly lower in the very low protein intake group (2 studies, 41 participants: MD -69.64 pmol/L, 95% CI -139.83 to 0.54).One study reported no significant difference in the number of deaths between low phosphorus intake and normal diet (279 participants: RR 0.18, 95% CI 0.01 to 3.82). Low phosphorus intake decreased serum phosphorus (2 studies, 359 participants: MD -0.18 mmol/L, 95% CI -0.29 to -0.07; I(2) = 0%).One study reported post-haemodialysis supplements did not increase serum phosphorus compared to normal diet (40 participants: MD 0.12 mmol/L, 95% CI -0.24 to 0.49).One study reported low phosphorus intake plus lanthanum carbonate significantly decreased FGF-23 (19 participants: MD -333.80 RU/mL, 95% CI -526.60 to -141.00), but did not decrease serum phosphorus (19 participants: MD -0.10 mg/dL, 95% CI -0.38 to 0.58) or PTH (19 participants: MD 31.60 pg/mL, 95% CI -29.82 to 93.02)., Authors' Conclusions: There was limited low quality evidence to indicate that dietary interventions (calcium-enriched bread or low phosphorus/protein intake) may positively affect CKD-MBD by increasing serum calcium, decreasing serum phosphorus, the calcium × phosphate product and FGF-23. Large and well-designed RCTs are needed to evaluate the effects of various interventions for people with CKD-MBD.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

Dipalmitoylphosphatidylcholine (DPPC) mono- and bilayers supported on mica surface were soaked for two weeks in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. Two solutions were investigated: with and without Tris. The experiment was conducted at 20°C and at a physiological temperature equal to 37°C. Raman spectroscopy was used for the characterization of the precipitated phosphate minerals. These studies may provide information about the physiological mineralization of cell membranes that are mainly composed of phospholipids. Findings from these experiments suggest that the DPPC bilayers enhance the formation of less soluble phosphate forms especially at a temperature of 37°C. In the solution without Tris temperature increase gives more mineral deposits. It is probably the hydrogen interactions between phosphate groups of the phospholipid and hydroxyl groups from Tris that lower exposure of the phosphate group to interact with calcium ions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.

Introduction: Vitamin D is vital in the regulation of the calcium-phosphate metabolism, has a direct impact on the musculoskeletal system, and also affects numerous other systems. Widespread vitamin D deficiency and its detrimental effect on health have been reported globally. Data concerning vitamin D status in Polish adult population is scarce., Material and Methods: Ambulatory patients of an outpatient clinic in Gdańsk were included in the study. Serum concentrations of 25(OH) D, parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium and phosphorus were determined. In a questionnaire declared UVB exposure, dietary vitamin D and calcium intake, and health status of the subjects were assessed. Non- and parametric tests, logistic regression and population attributable risk were applied in data analysis., Results: 448 adults were examined from February to mid-April 2012, 305 women and 143 men, aged 19 to 86 (mean 46.3 ± 14.9 years). Mean 25-hydroxyvitamin D concentration was 14.3 ± 6.6 ng/mL. 84.4% of subjects were vitamin D deficient (25(OH)D < 20 ng/mL); 13.2% presented insufficient (20-30 ng/mL), and 2.5% (or 11 subjects) sufficient 25(OH)D concentrations. Significantly higher 25(OH)D concentrations were found in subjects who reported more UVB exposure, supplemented vitamin D orally and those who declared more physical activity. 21% of subjects had elevated serum PTH concentration (i.e. > 62 pg/mL); mean parathormone was 48.6 ± 25.2 pg/mL. A linear correlation was found between the logarithm of PTH and logarithm of 25(OH)D concentrations (r = -0.21, p < 0.001)., Conclusions: Results obtained here demonstrate the necessity of implementing a monitoring and prophylaxis programme of vitamin D deficiency in Poland.

Background: Hyperphosphatemia, secondary hyperparathyroidism (SHPT) and anemia are common secondary complications in hemodialysis patients with end-stage renal disease (ESRD). Compared with conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been found to be more effective in patients with ESRD. The objective of this study was to determine whether sDHD could improve hyperphosphatemia, SHPT and anemia in patients with ESRD., Methods: Twenty-seven patients (11 women and 16 men, 46.8 ± 13.4 years old) were switched from CHD to sDHD. All hematologic parameters were measured prior to the switch (baseline), at 3 months after the switch (sDHD(1)) and at 6 months after the switch (sDHD(2))., Results: The serum phosphate decreased from 2.54 ± 0.32 mmol/L at baseline to 2.15 ± 0.36 mmol/L (p < 0.001) at sDHD(1) and 1.97 ± 0.33 mmol/L (p < 0.001) at sDHD(2). Calcium-phosphate product decreased from 5.18 ± 1.24 mmol(2)/L(2) at baseline to 4.20 ± 0.71 mmol(2)/L(2) (p < 0.001) at sDHD(1) and 4.02 ± 0.83 mmol(2)/L(2) (p < 0.001) at sDHD(2). The serum PTH levels decreased from 223.9 ± 124.7 pmol/L at baseline to 196.3 ± 101.3 pmol/L (p < 0.05) at sDHD(2). The hemoglobin concentration increased significantly from CHD to sDHD. However, the requirement for erythropoietin (EPO) dose decreased from 6847.8 ± 1057.3 u/week at baseline to 5869.6 ± 1094.6 u/week (p < 0.05) at sDHD(2)., Conclusions: sDHD may decrease serum phosphate, calcium-phosphate product and PTH, increase hemoglobin levels and decrease exogenous EPO dose requirements compared with CHD in hemodialysis patients.

Background: Fibroblast growth factor 23 (FGF23), with its co-receptor Klotho, plays a crucial role in phosphate metabolism. Several recent studies suggested that circulating FGF23 and α-Klotho concentrations might be related to cardiovascular abnormalities in patients with advanced renal failure., Purpose: Using data from 100 cardiology inpatients who were not undergoing chronic hemodialysis, the association of circulating levels of FGF23, α-Klotho, and other calcium-phosphate metabolism-related parameters with the left ventricular ejection fraction (LVEF) and left ventricular mass (LVM) was analyzed., Methods and Results: LVEF was measured using the modified Simpson method for apical 4-chamber LV images and the LVM index (LVMI) was calculated by dividing the LVM by body surface area. Univariate analysis showed that log transformed FGF23, but not that of α-Klotho, was significantly associated with LVEF and LVMI with a standardized beta of -0.35 (P<0.001) and 0.26 (P<0.05), respectively. After adjusting for age, sex, estimated glomerular filtration rate, and serum concentrations of intact parathyroid hormone, and 25-hydroxyvitamin D as covariates into the statistical model, log-transformed FGF23 was found to be a statistically positive predictor for decreased left ventricular function and left ventricular hypertrophy., Conclusions: In cardiology department inpatients, circulating FGF23 concentrations were found to be associated with the left ventricular mass and LVEF independent of renal function and other calcium-phosphate metabolism-related parameters. Whether modulation of circulating FGF23 levels would improve cardiac outcome in such a high risk population awaits further investigation.

Intermittent and low-dose parathyroid hormone (PTH) injection to stimulate bone formation has been used in the treatment of osteoporosis. The N-terminal fragment 1-34 of PTH is quite similar in structure and function to N-terminal PTH-related protein (PTHrP). PTH(1-34) and PTHrP also share a coreceptor, the PTH/PTHrP receptor. Therefore, some studies have suggested that PTHrP could effectively stimulate bone formation, similar to PTH. We used an ovariectomized (OVX) rat model of osteoporosis to study the effects of PTHrP(1-34) on bone metabolism by measuring bone mineral density (BMD), bone histomorphometrics, and biomechanical parameters. We found that subcutaneous injection of PTHrP(1-34) (40 or 80 μg/kg body weight every day) in OVX rats increased lumbar and femoral BMD, improved bone biomechanical properties, enhanced bone strength, and promoted bone formation. We selected 40 μg/kg as the preferred therapeutic dose of PTHrP(1-34) and investigated the effects of frequency of treatment (per 1, 2, 3, or 7 days) on bone metabolism in OVX rats. We found that injection of PTHrP(1-34) once per day or every other day significantly improved the BMD and strength of OVX rats. Serum calcium and phosphate levels in all treated rats did not vary significantly from control rats. Based on our results, intermittent low-dose PTHrP(1-34) injection promoted bone formation in OVX rats, suggesting a high potential for therapeutic use in osteoporosis patients.

Background: The aim of the present study was to examine the postprandial calcium and phosphate concentrations after supplementation with pentacalcium hydroxy-triphosphate (CaP)., Methods: Ten men participated in this double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. One group consumed bread enriched with CaP (plus 1 g calcium/d) and the other group a placebo product for three weeks. After a two week wash-out, the intervention was switched between the groups for another three weeks. Blood samples were drawn at the beginning (single administration) and at the end (repeated administration) of the intervention periods at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, a test meal, with or without CaP was consumed. The plasma concentrations of calcium and phosphate were examined. One participant dropped out due to personal reasons., Results: CaP supplementation resulted in a significantly higher plasma calcium concentration after 240 min compared to placebo. After repeated CaP administration, the AUC for the increment in plasma calcium concentration was significantly higher compared to placebo.After single and repeated CaP supplementation, plasma phosphate concentration significantly decreased after 30, 60, 120 and 180 min compared to 0 min. The placebo administration resulted in significant decreases after 30, 60 and 120 min compared to 0 min., Conclusion: Our results show that CaP contributes to an adequate calcium supply, but without increasing the plasma concentration of phosphate., Trial Registration: www.clinicaltrials.gov; NCT01296997.

Background: Fibroblast growth factor-23 (FGF-23), a novel marker of bone disease in chronic kidney disease (CKD) has been shown to correlate with vascular calcifications. We aimed to describe the effect of the calcium phosphate product (Ca*P) on FGF-23 concentrations in children and young adults without confounding cardiovascular disease., Methods: Pediatric and young adult patients with CKD stages I-V were recruited in this cross sectional study to measure FGF-23, cystatin C, vitamin D-metabolites and other serum markers of bone metabolism. FGF-23 levels were determined with an enzyme-linked immunosorbent assay. The association between FGF-23 and (Ca*P) was assessed using non-parametric methods. Patients were divided into two age groups, less than 13 years of age and greater than 13 years of age., Results: This cross-sectional study measured serum FGF-23, in 81 patients (42 females, 51.9%) at London Health Sciences Centre, aged 2 to 25 years, with various stages of CKD (Cystatin C estimated glomerular filtration rate, eGFR=10.7-213.0 ml/min). For the whole entire group of patients, FGF-23 levels were found to correlate significantly with age (Spearman r= 0.26, p=0.0198), Cystatin C eGFR (Spearman r=-0.40 p=0.0002), CKD stage (Spearman r=0.457, p<0.0001), PTH (Spearman r=0.330, p=0.0039), ionized calcium (Spearman r=-0.330, p=0.0049), CysC (Spearman r= 0.404, p=0.0002) and 1,25-dihydroxyvitamin D (Spearman r=-0.345, p=0.0034) concentrations. No significant correlation was found between FGF-23 levels and calcium phosphate product (Spearman r= 0.164, p=0.142). Upon classification of patients into two age groups, less than 13 years of age and more than 13 years of age, correlational results differed significantly. FGF-23 correlated with CysC eGFR( Spearman r= -0.633, p<0.0001), CKD stage (Spearman r=0.731, p<0.0001), phosphate (Spearman r= 0.557, p<0.0001), calcium phosphate product (Spearman r=0.534, p<0.0001), 125(OH)2 Vit D (Spearman r=-0.631, p<0.0001), PTH (Spearman r= 0.475, p=0.0017) and ionized calcium (Spearman r= -0.503, p=0.0015) only in the older group. The relationship between FGF-23 and Ca*P for the older group could be expressed by the exponential model FGF-23= 38.15 e0.4625Ca*P., Conclusion: Abnormal values of FGF-23 in adolescents and young adults with CKD correlate with Ca* P in the absence of vascular calcifications, and may serve as a biomarker for the risk of cardiovascular calcifications.

Aims: High calcium (Ca), phosphate (P), and Ca-P product (CPP) are associated with cardiovascular disease in patients with chronic kidney disease. Whether this relationship persists in individuals with normal kidney function is not yet elucidated. We explored the relationship of serum Ca, P, and CPP to coronary atherosclerosis assessed by cardiac computed tomography angiography (cCTA) in participants with normal kidney function., Methods and Results: This study included 7553 participants (52 ± 10 years, male 57%) with near-normal kidney function (estimated glomerular filtration rate > 60 mL/min/1.73 m2) who underwent cCTA. The relationship of Ca, P, and CPP to coronary atherosclerosis [coronary artery Ca score (CACS) >100 and the presence of coronary artery disease (CAD)] was evaluated. Higher Ca, P, and CPP were significantly associated with CACS > 100 continuously [adjusted odds ratio (OR) per mg/dL: Ca 1.21, P = 0.026; P 1.29, P < 0.001; CPP 1.03, P < 0.001]. However, they correlate only weakly with the presence of CAD (OR: Ca 1.17, P = 0.001; P 1.05, P = 0.173; CPP 1.01, P = 0.034). This discrepancy was because calcified or mixed plaque and non-calcified plaque (NCP) were included in CAD. A significant relationship was demonstrated between calcified or mixed plaque and Ca, P, and CPP (OR: Ca 1.20, P = 0.001; P 1.13, P = 0.003; CPP 1.02, P = 0.001), but not NCP., Conclusion: Elevated serum levels of Ca, P, and CPP are significantly associated with the presence of calcified coronary atherosclerotic plaque. It is unclear if there is a causal relationship. This relationship is thought to contribute to vascular calcification, but is less closely associated with NCP.

Glucocorticoids (GCs) are a large group of drugs used to treat a range of inflammatory, autoimmune and neoplastic diseases in dogs. Glucocorticoids have been linked to disturbances in calcium metabolism and skeletal disorders in humans, yet their effects at therapeutically effective dosages in dogs with spontaneous diseases are poorly understood. Serum concentrations of calcium, phosphate, vitamin D metabolites and plasma concentrations of parathyroid hormone and ionised calcium together with urinary fractional excretion of calcium and phosphate, were measured in 16 dogs with atopic dermatitis before and 6 weeks after standard dosage prednisolone treatment (0.93-1.06 mg/kg) every other day after 7 days of treatment with the same dosage once daily. The severity of their physical signs, as assessed by the canine atopic dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh Pruritus Scale (EPS), decreased in all dogs following prednisolone treatment. There was no significant difference in any of the biochemical parameters measured following prednisolone treatment. This study indicates that prednisolone, used at a therapeutically effective dose, has minimal impact on calcium metabolism in dogs with atopic dermatitis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

FGF23 is a circulating factor regulating TPR and is increased in CKD. After RT, it seems to induce phosphorus wasting in adults. Data on FGF23 after PRT are scarce. Parameters of bone metabolism including calcium, phosphate, 25-(OH) vitamin D, 1,25-(OH)(2) vitamin D, alkaline phosphatase, PTH, and FGF23 were analyzed in 57 children after PRT and 11 controls. Median time after PRT was 25.9 (range 2-135) months. eGFR after PRT ranged from 15 to 175 mL/min/1.73 qm. Mean (±s.e.) FGF23 and PTH levels were significantly elevated compared with controls (146 ± 30 vs. 43 ± 3 ng/L, p = 0.001 and 182 ± 42 vs. 74 ± 18 ng/L, p = 0.004, respectively). Highest FGF23 levels were found in children with an eGFR below 60 mL/min*1.73 sqm (280 ± 69 vs. 62 ± 5 ng/L, p = 0.001), but significantly elevated values were already present in CKD2T. In a multivariate analysis, eGFR, PTH, calcium, and phosphate were significantly associated with FGF23. In a subgroup of 17 patients (29.8%) with persistent hypophosphatemia, phosphate levels were significantly associated with FGF23 and not with PTH. FGF23 is increased in children after PRT, especially in patients with chronic allograft dysfunction, and seems to be a more sensitive marker of dysregulated calcium phosphate homeostasis than PTH., (© 2012 John Wiley & Sons A/S.)

Background: Hemodialysis (HD) is an important risk factor for progression of aortic valve stenosis (AS). However, there are varying degrees of disease progression among patients with AS on HD. The aim of this study was to find determinants of rapid progression of AS in patients on HD., Methods: We enrolled 30 patients with AS on HD with a mean follow-up period of 4 years. The peak pressure gradient (PPG) between the initial echocardiography and the last echocardiography at least 3 months interval (ΔPPG) was adopted as the indicator of AS progression. We divided the patients into two groups according to ΔPPG per year [rapid progression (ΔPPG>4.5 mmHg/year), slow progression (ΔPPG<4.5 mmHg/year)] and compared the clinical characteristics between the two groups., Results: Overall mean ΔPPG was 4.5 mmHg/year. Systolic blood pressure (SBP), serum calcium, and calcium-phosphate product were significantly higher in rapid progression group compared with slow progression group (p<0.05)., Conclusion: High systolic blood pressure, serum calcium, and calcium-phosphate product were associated with rapid progression of AS in patients on chronic HD., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The geometric features of bone graft substitutes, such as the pore and pore interconnection sizes, are of paramount importance for their biological performance. Such features are generally characterized by micro-computed tomography (μCT). Unfortunately, the resolution of μCT is often too limited. The aim of this study was to look at the effect of μCT resolution on the geometric characterization of four different bone graft substitutes. An attempt was also made to improve the characterization of these materials by applying a subvoxelization algorithm. The results revealed that both approaches increased the accuracy of the geometric characterization. They also showed that the interconnection size in particular was affected. Comparing the results obtained from the scanned and numerical subvoxelization datasets revealed a minor difference of less than 2.5% for the porosity values. The difference for the pore sizes was up to 10%. Considerable differences of up to 35-50% were found for the interconnection sizes. The present study demonstrates how complex geometric characterization is and how important it is for biomaterial researchers to be aware of the impact of μCT resolution on the pore and pore interconnection sizes., (Copyright © 2011. Published by Elsevier Ltd.)

Objective: To assess outcome in a cohort of patients with infantile hypercalcemia followed over 3 years., Study Design: Patients (n = 32) presenting to the calcium clinic between July 2002 and September 2008 were studied. In addition to tests of calcium phosphate metabolism, serum insulin-like growth factor-1, calcitonin, urine citrate, and calcium-sensing receptor gene analysis were obtained., Results: Mean age at presentation was 6.0 ± 6.3 months. Mean calcium level was 11.4 ± 0.7 mg/dL (2.84 ± 0.17 mmol/L). A recognized cause was found in 14% and a probable cause in 14% of the cohort. Those with nephrocalcinosis (n = 11) had significantly lower mean weight SDS and higher mean calcium levels. The biochemical profile of those in whom no cause could be determined included nonsuppressed parathyroid hormone with either normal or increased 1,25(OH)(2)D. Hypercalcemia resolved in 20 patients. However, in approximately a third, there was persistence in hypercalcemia, hypercalciuria, or nephrocalcinosis., Conclusions: The addition of 1,25(OH)(2)D and calcium-sensing receptor mutation analysis to a panel of investigations may improve diagnostic yield. Clinical outcome is overall good, however, one-third need ongoing follow-up., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Unlabelled: The main cause of resistance to erythropoiesis-stimulating agents (ESA) used for treatment of anemia in chronic hemodialysed patients (CHP) is the iron deficiency, absolute or functional. Secondary hyperparathyroidism (SHPT) is a secondary factor of resistance. Indeed, it has been reported in the literature an improvement of anemia parameters after surgical parathyroidectomy (PTX). The objective of this study is to assess in CHP, the impact of the correction of SHPT by a calcimimetic, cinacalcet (CI), (which is considered as a pharmacological PTX) on the response to ESA, measured by the erythropoietin resistance index (ERI). Twenty-two CHP with severe SHPT documented by an intact parathyroid hormone (iPTH) above 800pg/mL were included in this prospective pilot study. Mineral bone metabolism, anemia and nutritional parameters were measured baseline and after 6 months of treatment by CI. The effect on anemia was assessed at the end of study by the ERI, the change in Hb concentration, and the proportion of patients with Hb levels above 11g/dL., Results: At the end of study there was a significant decrease (M6 vs M0) in iPTH (1302 vs 674pg/mL or -48%, p=0.006), serum calcium (2.39 vs 2.15mmol/L or -10%), serum phosphate (2 vs 1.7mmol/L or -15%), serum calcium-phosphorus product (CaxP) (4.8 vs 3.8mmol(2)/L(2) or - 20% (p<0.05), and the number of patients with CaxP>4.4mmol(2)/L(2) (64 vs 32%, p<0.05). The level of bone alkaline phosphatase remained stable during the study (28 vs 27 IU/L). The Hb levels increased from 11 to 11.4g/dL, as did the proportion of patients whose Hb concentration reached 11g/dL or higher (50 vs 70%, p<0.05) without important change of the median weekly ESA dosis in the majority of patients, 18 cases (81%) vs four (19%). Two subgroups were identified from the median decreases in iPTH (delta iPTH) between M0 and M6, Group 1 (delta iPTH≥400pg/mL, n=10) and group 2 (delta iPTH<400pg/mL, n=12): in group 1, we found a correlation between the decrease in iPTH by CI and the stability or decrease in ERI (group 1), at comparable dose of dialysis, nutritional and iron intakes and inflammatory profiles; in group 2 without a significant effect of CI on PTH reduction the levels of ERI and ESA dosis were more elevated., Conclusion: A treatment by calcimimetic improves the control of anemia by ESA in CHP and interferes positively on a cause of secondary resistance to ESA represented by SHPT. The mechanism of these effects could be linked to the decreased of bone marrow fibrosis and inflammation and to the triptych formed by the reduction in iPTH, CaxP and phosphate., (Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Secondary hyperparathyroidism is associated with an increased risk of skeletal fractures and mortality in dialysis patients. Classical treatments such as active vitamin D derivatives and surgical parathyroidectomy are efficient but have some limitations. Second generation calcimimetics allow to control serum PTH levels without increasing serum calcium phosphorus product. This article reviews the physiological bases of PTH regulation, the mode of action of calcimimetics and the results of preclinical and clinical studies evaluating the effect of calcimimetics on different biochemical, clinical and histological parameters., (Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Objective: To review the target levels of calcium (Ca), phosphate (P), calcium phosphate products (Ca × P) and intact parathyroid hormone (iPTH) levels in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) and compare them with the Kidney Disease Outcome Quality Initiative (K/DOQI) recommendations., Subjects and Methods: Three hundred and fifty-seven patients who had been undergoing dialysis for more than 3 months were included. Patients who had undergone a parathyroidectomy were excluded. The levels of Ca, P, iPTH and Ca × P were monitored for the last 3 months. The Ca and P levels were measured by standard techniques, and iPTH was assessed by the intact molecule assay., Results: Between HD and PD patients, there was no statistically significant difference for age, duration of dialysis or primary disease causing end-stage renal disease. The percentage of patients whose serum Ca, P, Ca × P product and iPTH were within K/DOQI recommended target ranges were 61.2, 66.4, 82.2 and 28.3% in HD patients, and 56.3, 60.6, 85.9 and 22.5% in PD patients, respectively. When all results for each group - HD and PD - were analyzed, 12.8% of patients had all 4 markers within the target range., Conclusion: Achieving target ranges of mineral markers is important in dialysis patients, but reaching K/DOQI target levels is difficult. Hence, physicians should be careful in using P binders and vitamin D analogs to achieve the normal ranges., (Copyright © 2010 S. Karger AG, Basel.)

Background and Objectives: The calcimimetic cinacalcet (Mimpara) was approved in the European Union in 2004 for treatment of secondary hyperparathyroidism (sHPT). This observational trial was conducted to investigate efficacy of cinacalcet and practices of sHPT treatment under routine clinical conditions., Patients and Methods: 913 patients on maintenance hemodialysis were recruited from 136 German kidney centers. 662 patients who fulfilled the entry criteria of moderate to severe sHPT (intact parathyroid hormone, iPTH: 300 - 800 pg/mL or 32 - 85 pmol/l) were included in the trial. Primary objective was to investigate efficacy of cinacalcet in patients treated for at least 160 days (efficacy collective, N = 555). The primary endpoint was defined as the percentage of patients with a iPTH within 150 - 300 pg/ml and a calcium-phosphate product (CaxP) ≤ 4.44 mmol (2)/l (2) (55 mg (2)/dl (2)) after 6 months of treatment. Further objectives were the course of calcium (Ca) and phosphate (P) as well as the use of phosphate binders and vitamin D in treatment of bone metabolism disorders., Results: According to the predefined entry criteria none of the patients reached the combined target criterion for iPTH and CaxP at baseline. The mean initial iPTH and CaxP were 530.0 ± 134.3 pg/mL and 4.82 mmol (2)/L (2) (mean ± SD) respectively. In spite of the unfavorable prognostic factors 25 % of the recruited patients met the combined target at the end of the trial. The mean reduction per patient for iPTH was 203.6 pg/mL [95 % confidence interval (CI) 183.3 - 224.0] and 0.69 mmol (2)/L (2) [95 %-CI 0.57 - 0.79] for CaxP. Ca and P were reduced by 5.3 % [95 %-CI 4.3 - 6.3] and 5.5 % [95 %-CI 3.4 - 7.7], respectively. The mean daily dose of cinacalcet at trial end was 44.9 ± 25.0 mg (mean ± SD). At baseline, 90 % of patients who were analyzed for efficacy (n = 500/555) were treated with phosphate binders, 57 % were treated with a calcium-based phosphate binder (n = 317/555). The use of active Vitamin D (all active Vitamin D compounds) was recorded for 59 % of the patients (n = 328/555). No relevant changes of these treatments were observed in the course of the trial. Tolerability of cinacalcet was good, 94 adverse drug reactions were recorded in 57 of the 913 enrolled patients (6 %)., Conclusions: One out of four patients reached the combined target of iPTH and CaxP with relatively low dose cinacalcet after 6 months of treatment. iPTH, Ca and P were reduced. The results confirm the high efficacy of cinacalcet in treatment of sHPT and underline the role of cinacalcet in the control of Ca and P., (© Georg Thieme Verlag KG Stuttgart · New York.)

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized-controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty-one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium-phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long-term cardiovascular and bone-related outcomes requires further investigation.

Background: The change in the demographics and the presence of multiple risk factors and co-morbidities in UK patients starting dialysis may lead to poor survival on dialysis. Many of these risk factors are present in the pre-dialysis period allowing a potential window of opportunity to intervene with risk modification measures., Aim: To examine various potential factors that may predict early and overall mortality., Design and Methods: We carried out an observational prospective study of a cohort of incident patients starting dialysis in a UK centre. Univariate analysis of factors and co-morbidities potentially affecting survival on dialysis were analysed to potential predictors. Factors affecting 1 year mortality were analysed using the t-test, the Mann-Whitney U-test or the chi-square test as appropriate. Mortality over the 5-year follow-up period was analysed using the Kaplan-Meier method., Results: Ninety-four patients [predominantly Caucasian (98%)], of mean age 63 years (15.6) (56% > 65 years) with a slight male preponderance were studied. Vascular disease (39%) and sepsis (33%) accounted for most of the deaths and a significant proportion of mortality was seen in the first year (56%). Patients with early mortality were older (68 vs. 61 years, P = 0.05) with lower haemoglobin (8.4 vs. 9.4 g/dl, P = 0.01) at the start of dialysis, commenced dialysis with a lower eGFR (5.4 vs. 6.5 ml/min/1.73 m(2), P = 0.06) and had more peripheral vascular disease (PVD) (39% mortality in patients with PVD vs. 18.5% in those without PVD, P = 0.04). Diabetes mellitus, high calcium phosphate product, older age and presence of vascular co-morbidities including ischaemic heart disease and peripheral vascular disease were associated with overall mortality over the 5-year follow-up period., Summary: In this study, elevated calcium phosphate product and diabetes mellitus in addition to the presence of vascular disease were associated with poor survival. Patients with low haemoglobin and lower first pre-dialysis eGFR suffered higher early mortality. These potentially modifiable factors that could be identified in the pre-dialysis stage provide a valuable opportunity for intervention.

Atherosclerotic vascular diseases are a major cause of morbidity and mortality for end-stage renal disease patients. We followed prospectively 226 hemodialysis patients by carotid ultrasonography to determine if ultrasonographic markers are predictive of the prognosis of these patients. The end-point was death or completion of the five-year follow-up period. Fatal cerebrovascular and cardiovascular events were the most common cause of death. By multivariate analysis, diabetes mellitus (DM) (P=0.005), plaque number (PN) by ultrasonography (P=0.023), age (P=0.001), calcium-phosphate product (P=0.049), and serum albumin (P=0.009) were extracted as independent risk factors. The five-year increase of PN was significantly greater for DM patients than for non-DM patients. Moreover, PN was an independent marker of a fatal event, irrespective of DM status. Our results suggest that PN may be a useful predictor of the long-term prognosis of hemodialysis patients.

Background: The K/DOQI guidelines recommend the use of albumin-corrected calcium (Ca), phosphate, parathyroid hormone (PTH) and calcium-phosphate product as therapeutic targets. The two most common assays for measuring albumin yield discordant results in uraemic patients, the Bromcresol purple (BCP) method providing lower albumin values than the Bromcresol green one (BCG). The aim of this study was to assess the impact of the assay on corrected Ca and, thus, on reaching recommended K/DOQI targets for corrected Ca and CaxP product., Methods: We measured plasma albumin (both by BCG and BCP), total Ca and phosphate in all our chronic hemodialysis (HD) patients. Total Ca was corrected ("adjusted") for albumin level by a formula proposed by the K/DOQI., Results: 89 patients were included, aged 71.2 +/- 11.5 years, on chronic hemodialysis for 29 (1-362) months. Albumin level was 3.78 +/- 0.24 g/dL by BCG and 3.12 +/- 0.27 by BCP ( p < 0.0001). Based on BCG albumin levels there were 12 cases of "hypocalcaemia" (<8.6 mg/dL), 3 cases of "hypercalcaemia" (>10 mg/dL) and 74 cases with "normal" Ca. The corresponding albumin levels were 3.9 +/- 0.2; 3.1 +/- 0.6 and 3.8 +/- 0.2 g/dL, respectively. According to BCP albumin levels, only one patient was labelled as hypocalcaemia , 21 as hypercalcaemia et 67 as "normal" adjusted Ca (albumin 3.1; 3 +/- 0.3 and 3.2 +/- 0.3 g/dL, respectively). Depending on the use of BCG or BCP, a discrepancy was thus observed in 29 cases (32.6%): 18 cases were classified as hypercalcaemia when albumin was measured by BCP but were considered normal using BCG, whereas 11 cases classified as hypocalcaemia with BCG had normal adjusted Ca with BCP. Concerning CaxP product, 7 discrepancies were detected., Discussion and Conclusion: The choice of either BCG or BCP has a major impact on albumin-adjusted Ca and thus on reaching K/DOQI targets for Ca and CaxP product. Clinicians should take this fact into account for the interpretation of laboratory values and the prescription of drugs related to mineral metabolism and dialysate calcium concentration. The type of assay used for the measurement of albumin should also be recorded and its impact taken into account (or corrected) in multicentric studies and registries.