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Background Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD. Study Design Network meta-analysis. Setting & Population Adults with CKD. Selection Criteria for Studies Randomized trials with allocation to phosphate binders. Interventions Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium. Outcomes The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification. Results 77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium. Limitations Limited testing of consistency; short follow-up. Conclusions There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials.

Background Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. Methods For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2–8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. Results In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. Conclusions These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Background and objectives The short-term effects of low-phosphate diets on fibroblast growth factor 23 (FGF23) level and the optimal amount of dietary phosphate restriction in patients undergoing hemodialysis remain unknown. Design setting, participants, & measurements This was a randomized, active-controlled trial with a crossover design that included 35 adults with ESKD undergoing thrice-weekly hemodialysis and with a serum phosphate level >5.5 mg/dl or between 3.5 and 5.5 mg/dl with regular phosphate binder use at a hemodialysis unit of tertiary teaching hospital in Taiwan. Subjects were randomized 1:1 to receive a very-low-phosphate diet, with a phosphate-to-protein ratio of 8 mg/g, or a low-phosphate diet, with a phosphate-to-protein ratio of 10 mg/g for 2 days, each with a 5-day washout during which subjects adhered to their usual diet. The primary outcome measure was mean difference in change-from-baseline intact FGF23 level between intervention groups. Secondary outcomes included difference in change-from-baseline serum phosphate, intact parathyroid hormone (PTH), and C-terminal FGF23 level between intervention groups. Results There was no significant difference in the mean change-from-baseline in intact FGF23 levels between the two study diets. The very-low-phosphate diet significantly lowered serum phosphate (mean difference, 0.6 mg/dl; 95% confidence interval [95% CI], 0.2 to 1.0; P=0.002). There were no significant differences in change-from-baseline intact PTH and C-terminal FGF23 levels between the two study diets. Conclusions Over the 2-day period, the FGF23-lowering effect of the very-low-phosphate diet is similar to that of the low-phosphate diet. The very-low-phosphate diet has an additional phosphate-lowering effect compared with the low-phosphate diet.

OBJECTIVE:The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. DESIGN:Historical cohort analyses of de-identified electronic medical records. SUBJECTS:In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. MAIN OUTCOME MEASURES:Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5mg/dL) and mean number of PB pills/day. RESULTS:Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P&nbsp

Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD.

Tumor epidemiology, as well as tumor microenvironments and cancer cell signaling study, has been presented with statistical relevance of inorganic phosphate (Pi) to tumorigenesis. Although serum Pi is still not acknowledged as a clinical tumor biomarker, abnormally high Pi concentration in serum or tumor lesions is gradually recognized as a characteristic of malignancy. On the other hand, phosphate binder (e.g. La2 (CO3)3, Fosrenols) has been clinically approved to treat hyperphosphatemia, a metabolic disease characterized by a high serum phosphate level. We hypothesize that, if reducing phosphate burden comes to benefit tumor therapy, could systemic or intratumoral administration of phosphate binder effectively deprive tumor Pi concentration, and then inhibit tumor growth and metastases? From the past clinical and preclinical outcomes, we’d conclude that Pi is not only a metabolite during tumor growth but also a force to trigger tumor progression and metastases. Two types of cancer models were developed to initiate this study. Firstly, a patient-derived xenograft mouse model of colorectal cancer was designed, where mice were administered systemically or intratumorally with lanthanum acetate (a molecular phosphate binder), and the serum or intratumoral Pi concentration levels were found to a dropdown. Secondly, a rabbit VX2 liver tumor was set up for the local-regional therapy model, where lanthanum acetate was intratumorally administered by the standard transcatheter arterial chemoembolization procedure, and it significantly reduced intratumoral Pi concentration. Therefore, Pi deprivation by phosphate binder might be a new anticancer strategy if reducing phosphate burden could effectively arrest tumor growth and delay metastatic progression.

Iron deficiency, anemia, hyperphosphatemia, and increased fibroblast growth factor 23 (FGF23) are common and interrelated complications of chronic kidney disease (CKD) that are linked to CKD progression, cardiovascular disease and death. Ferric citrate is an oral phosphate binder that decreases dietary phosphate absorption and serum FGF23 concentrations while increasing iron stores and hemoglobin in patients with CKD. Here we compared the effects of ferric citrate administration versus a mineral sufficient control diet using the Col4a3 knockout mouse model of progressive CKD and age-matched wild-type mice. Ferric citrate was given to knockout mice for four weeks beginning at six weeks of age when they had overt CKD, or for six weeks beginning at four weeks of age when they had early CKD. Ten-week-old knockout mice on the control diet showed overt iron deficiency, anemia, hyperphosphatemia, increased serum FGF23, hypertension, decreased kidney function, and left ventricular systolic dysfunction. Ferric citrate rescued iron deficiency and anemia in knockout mice regardless of the timing of treatment initiation. Circulating levels and bone expression of FGF23 were reduced in knockout mice given ferric citrate with more pronounced reductions observed when ferric citrate was initiated in early CKD. Ferric citrate decreased serum phosphate only when it was initiated in early CKD. While ferric citrate mitigated systolic dysfunction in knockout mice regardless of timing of treatment initiation, early initiation of ferric citrate also reduced renal fibrosis and proteinuria, improved kidney function, and prolonged lifespan. Thus, initiation of ferric citrate treatment early in the course of murine CKD lowered FGF23, slowed CKD progression, improved cardiac function and significantly improved survival.

Over the last few decades, innovative wood composite products and processes have created markets for new and existing products. Inorganic bonded fibre composites have been developed for high performance applications using conventional cement and concrete. The demands for wood based composites along with increasing economic and environmental concerns on conventional wood products necessitate moving beyond the traditional processing methods to more cost-effective and environmentally friendly approaches. In the wake of the twenty-first century, a fast-setting phosphate binder with a low carbon footprint was developed, which can alternatively be utilized in wood composite development. This paper reviews the recent progress in phosphate bonded composite products, based on published literature from the last two decades. A brief background on Portland cement based natural fibre composites is presented. In addition, the mechanism of the formulation of phosphate binders, the effect of aggregates in the materials and the environmental benefits accruable to such materials are discussed. Development of low-carbon footprint binder for wood composites

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies.

Guidelines restricting use of calcium-based phosphate binders in all patients with end-stage renal disease owing to their potential contribution to increased cardiovascular risk shifted prescribing from calcium acetate toward the costlier sevelamer carbonate products.To compare cardiovascular events and mortality between patients with end-stage renal disease (ESRD) undergoing hemodialysis receiving sevelamer vs calcium acetate in real-world practice.An observational cohort study was conducted using the United States Renal Data System linked to Medicare claims data (May 1, 2012, to December 31, 2013). Data analysis was performed from October 2017 to September 2018. Participants included patients 65 years or older with ESRD within 180 days after starting hemodialysis (sevelamer, 2647; calcium acetate, 2074).New use of sevelamer (calcium-free phosphate binder) vs calcium acetate (calcium-based phosphate binder).Hazard ratios (HRs) with 95% CIs were estimated for fatal or nonfatal cardiovascular events (myocardial infarction or ischemic stroke: primary outcome) and all-cause mortality (secondary outcome) using Cox proportional hazards regression with fine stratification on the propensity score to control for potential confounders, including phosphorus and calcium levels.After propensity score weighting, 2639 patients initiating sevelamer treatment (1184 men [44.9%]; mean [SD] age, 75.6 [6.9] years) and 2065 patients initiating calcium acetate treatment (930 men [45.0%]; mean [SD] age, 75.5 [7.1] years) were included in the analysis. Crude incidence rates (IRs) for cardiovascular events of 458 per 1000 person-years for sevelamer and 464 per 1000 person-years for calcium acetate were observed. After propensity score fine-stratification weighting, HRs of 0.96 (95% CI, 0.84-1.10) for cardiovascular events were observed. Results were consistent within subgroups of age (75 y: primary outcome, HR, 1.02; 95% CI, 0.85-1.24; vs ≥75 years: primary outcome, HR, 0.83; 95% CI, 0.69-1.01) and sex (primary outcome in men: HR, 1.02; 95% CI, 0.83-1.26).The results of the study do not suggest increased cardiovascular safety of sevelamer in the routine clinical practice of patients with ESRD compared with calcium acetate; this study's findings suggest that well-designed, long-term, randomized clinical trials are needed.

Recent clinical studies demonstrated the favorable effects of calcium-free phosphate binders on mortality and vascular calcification in hemodialysis (HD) patients. The aim of the present study was to investigate the effects of a calcium-free phosphate binder, lanthanum carbonate (LC), on bone metabolic markers and bone mineral density (BMD), compared with those of calcium carbonate (CC), in subjects new to HD. The present study included 65 subjects from our previous randomized controlled trial (LC group, N = 31; CC group, N = 34). We investigated the effects of LC on serum intact parathyroid hormone (iPTH), osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b), sclerostin levels, and BMD, compared with those of CC in patients new to HD at baseline and at 12 and 18 months. Serum OC levels at 18 months were significantly higher in the LC group than in the CC group. During the study period, serum BAP and TRACP-5b and iPTH levels tended to be higher in the LC group than in the CC group. At 18 months, the percentage of low bone turnover, based on a serum BAP cutoff value, was significantly lower in the LC group than in the CC group. There were no significant differences in the lumbar and femoral BMD between the two groups. The results of the present study suggest that LC has potential in preventing low bone turnover, in comparison to CC, in patients new to HD.

Background Adherence to phosphate binder treatment is important to prevent high serum phosphate level in chronic dialysis patients. We therefore wanted to investigate patient knowledge, beliefs about and adherence to phosphate binders among these patients and assess whether one-to-one pharmacist-led education and counselling enhance adherence and lead to changes in serum phosphate levels. Methods A descriptive, interventional, single arm, pre-post study was performed at a hospital in Norway, including chronic dialysis patients aged 18 years or more using phosphate binders. The primary end-point was change in the proportion of patients with serum phosphate below 1.80 mmol/L and the secondary end-points included change in the patient’s knowledge, beliefs and adherence after the intervention measured by completion of questionnaires ‘Patient Knowledge’, Medication Adherence Report Scale (MARS− 5) and Beliefs about Medicines Questionnaire (BMQ). Data was collected both prior to and after one-to-one pharmacist-led education and counselling about their phosphate binders. Other medicines used by the patient was also registered. Results A total of 69 patients were enrolled in the study. After intervention, the probability of serum phosphate being below the target threshold 1.80 mmol/L (5.58 mg/dL) increased, although no significant change in mean serum phosphate levels was seen. On the other hand, the knowledge regarding phosphate binder treatment and the patients’ beliefs about the necessity of the treatment increased, while the concerns decreased (BMQ). This effect did not lead to increase in self-reported adherence measured by MARS-5. However the scores were high before the intervention. Conclusions Short term one-to-one individualized pharmacist-led education and counselling about phosphate binders increased the probability of serum phosphate concentrations being below the target threshold level 1.80 mmol/L (5.58 mg/dL), although not statistically significant. However, it did not decrease the mean serum phosphate level or increase the patients’ self-reported adherence. The patients increased their knowledge about the phosphate binder and their understanding of adherence, and were less concerned about the side effects of the medication. Trial registration ISRCTN52852596 , registered 11 April 2019. The trial was registered retrospectively.

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance.

Lanthanum carbonate is a phosphate binder that is used to reduce serum phosphate levels in patients with end-stage renal disease (ESRD). Lanthanum forms insoluble lanthanum phosphate complexes that are supposed to pass through the gastrointestinal (GI) tract unabsorbed. Phosphate binders have been reported to deposit in the GI tract and can cause mucosal injury. There are few case reports of GI bleeding associated with phosphate binder deposits. This case report presents a patient with iron deficiency anaemia secondary to biopsy-proven lanthanum deposits in the upper GI tract. There were no overt signs of active GI bleeding. Patient’s anaemia improved with discontinuation of the phosphate binder. Lanthanum could be a hidden cause of resistant anaemia among patients with ESRD through asymptomatic GI blood loss.

Iron deficiency anemia (IDA) is a frequent complication of chronic kidney disease (CKD) and is associated with adverse outcomes in these patients. Patients with CKD and IDA remain largely undertreated. Conventional oral iron agents are insufficiently effective due to poor absorption and cause gastrointestinal side effects; thus, novel oral iron preparations are needed. This article covers current treatment guidelines for patients with anemia and CKD and clinical trial data for iron-repletion agents currently in use, as well as for novel oral iron therapies in development. Ferric citrate, a novel oral iron-repletion agent approved for patients with non-dialysis-dependent CKD and IDA, demonstrated improvements in hemoglobin levels and iron parameters, with good tolerability in patients with non-dialysis-dependent CKD. When used as a phosphate binder, ferric citrate also improves hemoglobin and iron parameters in dialysis-dependent CKD, but additional trials are needed to evaluate its efficacy as an iron-repletion agent in this setting. Other novel oral iron preparations in development for IDA in patients with CKD include ferric maltol, which is approved in Europe and the United States for IDA in adult patients, and sucrosomial iron, which has been evaluated in IDA associated with CKD and several other clinical settings.

Reduced renal excretion of phosphate leads to hyperphosphatemia, which is prevalent in patients with end-stage renal disease, and is associated with increased morbidity and mortality. Dialysis alone is unable to adequately remove the ingested phosphate contained in food. It is therefore usually necessary to supplement food with drugs that reduce the intestinal absorption of dietary phosphate in order to control serum phosphate. Lanthanum carbonate is a recently introduced nonaluminum, noncalcium phosphate binder licensed for the management of serum phosphate in end-stage renal failure. It appears safe and effective, with data demonstrating no toxic effects in man after continuous exposure for up to 6 years. It is well tolerated and has a positive effect on bone histology in the context of renal osteodystrophy. Lanthanum carbonate's high affinity for phosphate rapid binding, palatability, low pill burden and absence of evident toxicity compare favorably with what are considered to be the ideal characteristics of an oral phosphate binder.

Kathryn Gray,1 Linda H Ficociello,2 Abigail E Hunt,1 Claudy Mullon,2 Steven M Brunelli1 1DaVita Clinical Research, Minneapolis, MN, USA; 2Medical Department, Fresenius Medical Care Renal Therapies Group, Waltham, MA, USA Background: Phosphate binders are widely used to achieve serum phosphorus control in patients with end-stage renal disease. However, the large pill burden associated with these medications may decrease adherence to therapy. In clinical trials, sucroferric oxyhydroxide (SO) demonstrated equivalent control of serum phosphorus to sevelamer, with a lower daily pill burden. We examined changes in phosphate binder pill burden, medication possession ratio (MPR), and phosphorus control among in-center hemodialysis (ICHD) patients converting to SO from another phosphate binder as part of routine care. Materials and methods: Patients included in this retrospective analysis (N=490) were ≥18 years old, received ICHD at a large dialysis organization (LDO), and were enrolled in the LDO’s pharmacy service. Patients converting to SO were those who had supply of another phosphate binder, received a first prescription fill for SO, and subsequently did not refill the non-SO phosphate binder. Patients were followed over the 6 months before and 6 months following the first SO fill and were censored from the analysis upon modality change, loss to follow-up, discontinuation of SO, or fill of a prescription for another phosphate binder after SO initiation (number censored=361). Outcome measures assessed were total phosphate binder pill burden and MPR, serum phosphorus, and percentage of patients with serum phosphorus ≤5.5 mg/dL. Results: Among patients converting to SO, mean phosphate binder pill burden was 10.8 pills/day during baseline; this decreased to 5.5 pills/day during follow-up (P

Background Hyperphosphatemia is a common consequence in end stage renal disease. It is associated with increased cardiovascular risk and mortality, also development of hyperparathyroidism and mineral bone disease. A patient educational program involving physician, pharmacist and dietician was developed to manage hyperphosphatemia among hemodialysis patients. Objective To investigate the efficacy of the program in optimal phosphate control among hemodialysis patients. Setting Kuala Lipis Hospital, Malaysia. Method This was a non-randomized, single-arm community trial running for a period of 6 months. The program consisted of a small group seminar and individual counseling sessions. Two individual counseling sessions were conducted for each patient, focusing on diet and medication adherence, by an accredited dietician and pharmacist respectively. The group seminar was delivered by a multidisciplinary team involving a physician, pharmacist and dietician. Topics included basic knowledge of hyperphosphatemia, phosphate binder and dietary phosphate control. Eligible and consented patients had knowledge and medication adherence assessment, measurement of pre-dialysis serum calcium, albumin, phosphate, haemoglobin and alkaline phosphatase before and after the educational program. Main outcome measure Phosphate level, knowledge and medication adherence assessment. Results Fifty-seven patients completed the program and were included into final data analysis. The median (IQR) phosphate level (mmol/L) was 1.86 (1.45–2.24) before and decreased to 1.47 (1.21–1.91) and 1.49 (1.28–1.81) 3 months and 6 months after PEP (p

Разработана технология получения теплоизоляционных смесей (ТИС) на основе диатомита Ильинского месторождения с применением фосфатных связок. Применение ТИС является одним из наиболее значимых методов энергосбережения, а также имеет важное технологическое значение. Наиболее эффективным способом дает улучшение теплоизоляционных свойств металла, позволяет снизить скорость охлаждения расплава, а также способствует распределению металла в ковшах, которое происходит благодаря добавлению веществ, не относящихся к металлу. A technology has been developed for the production of heatinsulating mixtures (HIM) based on diatomite. The use of HIM is one of the most significant methods of energy conservation, and also has important technological significance. The most effective way is to improve the thermal insulation properties of the metal, which allows to reduce the cooling rate of the metal, which also occurs due to the addition of substances not related to the metal.

Aim Hyperphosphataemia is associated with increased mortality and morbidity in end stage renal disease. Despite phosphate binder therapy, a large proportion of patients do not reach the treatment target. In five contemporary binders we explored the influence of pH and phosphate concentration on phosphate binding. This interaction could be of relevance in clinical practice. Methods Phosphate binding was quantified in vitro in 25 mL of purified water containing phosphate concentrations of 10, 15 and 20 mM and baseline pH values of 3.0 or 6.0, with a binder over 6 h. Lanthanum carbonate, calcium acetate/magnesium carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide, 67 mg of each, were used. The experiments were performed in duplicate. The primary outcome was the difference in the amount of bound phosphate for each binder after 6 h in solutions at two different pH values. Secondary outcomes were the influence of phosphate concentration on phosphate binding, next to binding patterns and phosphate binder saturation. Results and Conclusion In this specific in vitro setting, lanthanum carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide bound more phosphate in the solution with baseline pH of 3.0. Differences however were small except for lanthanum carbonate. Calcium acetate/magnesium carbonate was most effective in a solution with baseline pH of 6.0. All phosphate binders bound more phosphate in solutions with higher concentrations of phosphate. Sevelamer carbonate, calcium acetate/magnesium carbonate and sucroferric oxyhydroxide bound most phosphate in the first hour and reached maximum binding capacity in less than 6 h., Summary at a Glance This study assesses the efficacy of five phosphate binders in vitro, in relation to pH, phosphate concentration and exposure time. Except for calcium acetate/magnesium carbonate, all binders were more effective at lower pH, and binding by lanthanum carbonate doubled at pH 3 versus pH 6. This highlights the clinically important impact of gastric acidity on phosphate binding.

Summary Background and aims Hyperphosphatemia constitutes one of the major problems faced by patients with chronic kidney disease, and nourishment plays a significant role in its control. The present study aimed to evaluate the maintenance of phosphorus serum levels by observing measurements before and after an intervention using the Phosphorus Counting Table (PCT), in hemodialysis patients lacking phosphate binder use. Methods The assessment included fifty individuals on hemodialysis who underwent phosphate binder suspension 30 days prior to the intervention. The participants received food and nutrition education on the PCT tool, which assists in the control of dietary phosphorus intake, and followed its instructions for two months. Fasting blood samples were collected at three moments for phosphorus, total calcium, and parathyroid hormone (PTH) analysis. The study sample was initially analyzed as a whole, then sub-classified into two groups: adherence and non-adherence. Results At the end of the study, no significant difference in serum phosphorus was observed in the total and the adherence groups (p > 0.05). The non-adherence group showed a substantial increase of 0.74 mg/dL in serum phosphorus levels and 6.16 mg2/dL2 in the calcium-phosphorus product after the intervention. Meanwhile, the calcium-phosphorus product improved from 56.42 ± 11.49 mg2/dL2 to 51.05 ± 10.67 mg2/dL2 in the adherence group. Serum calcium levels did not change throughout the study in the three groups. A significant increment in PTH serum levels was observed at the end of the study in all groups. Conclusion The PCT showed to be efficient in the maintenance of serum phosphorus in the individuals who adhered well to the tool, without the administration of phosphate binders. Such a method can assist in patient adherence to treatment and enables better diet flexibility. The present trial was registered under the Brazilian Clinical Trials Registry (Rebec). Registration number: RBR-2vzd48.

This study aims to describe the regional variance in prescriptions for chronic kidney disease (CKD) medications and to analyze regional characteristics to identify the sources of these differences by utilizing the National Database of Health Insurance Claims, which provides more than 95% of nationwide claim information for Japan. Data regarding the total claimed amount for phosphate binders (PBs), erythropoiesis-stimulating agents (ESAs), carbonaceous adsorbents, and potassium-lowering agents in fiscal year 2015 were obtained. Correlation coefficients were calculated for the claimed amount of these drugs per CKD patient and social and medical variables, including the percentage of the population aged ≥ 65 years and the numbers of hospital beds and certified nephrologists. Subsequent multiple regression analysis was performed using explanatory factors affecting the amount of PB or ESA prescriptions per CKD patient. The total claimed amounts were 585,485,115 for PBs and 2,373,777 for ESAs. Variations in the claimed amount per CKD patient among 47 prefectures were 4.9-, 6.1-, 6.6-, and 6.0-fold for PBs, ESAs, carbonaceous adsorbents and potassium-lowering agents, respectively. The number of nephrologists per CKD patient was positively correlated with the prescribed amount for PBs and ESAs per CKD patient, and independently associated with the prescribed amount also in regression analysis. Substantial regional variation in CKD-related drug prescriptions exists even within a uniform health care system. The number of certified nephrologists was associated with the prescribed amount for PBs and ESAs. Further studies are needed to clarify whether geographic distribution of certified nephrologist may affect clinical practice pattern.

INTRODUCTION Phosphate balance could be reached only by an optimized combination of dietary restriction and the careful use of phosphate binders for patients receiving standard hemodialysis treatment. Little is known about individual variability of phosphorus intake and phosphate binder use in hemodialysis patients. The purposes of this study were to quantify phosphorus intake and to describe individual phosphate-binder use in hemodialysis patients. METHODS This was a cross-sectional study. The dietary phosphorus intake was assessed using a 3-day duplicate portion sampling method combined with chemical analysis. Patients' adherence to phosphate binders was evaluated by the Morisky Medication Adherence Scale, with a score of

Iron deficiency, anemia, hyperphosphatemia, and increased fibroblast growth factor 23 (FGF23) are common and interrelated complications of chronic kidney disease (CKD) that are linked to CKD progression, cardiovascular disease and death. Ferric citrate is an oral phosphate binder that decreases dietary phosphate absorption and serum FGF23 concentrations while increasing iron stores and hemoglobin in patients with CKD. Here we compared the effects of ferric citrate administration versus a mineral sufficient control diet using the Col4a3 knockout mouse model of progressive CKD and age-matched wild-type mice. Ferric citrate was given to knockout mice for four weeks beginning at six weeks of age when they had overt CKD, or for six weeks beginning at four weeks of age when they had early CKD. Ten-week-old knockout mice on the control diet showed overt iron deficiency, anemia, hyperphosphatemia, increased serum FGF23, hypertension, decreased kidney function, and left ventricular systolic dysfunction. Ferric citrate rescued iron deficiency and anemia in knockout mice regardless of the timing of treatment initiation. Circulating levels and bone expression of FGF23 were reduced in knockout mice given ferric citrate with more pronounced reductions observed when ferric citrate was initiated in early CKD. Ferric citrate decreased serum phosphate only when it was initiated in early CKD. While ferric citrate mitigated systolic dysfunction in knockout mice regardless of timing of treatment initiation, early initiation of ferric citrate also reduced renal fibrosis and proteinuria, improved kidney function, and prolonged life span. Thus, initiation of ferric citrate treatment early in the course of murine CKD lowered FGF23, slowed CKD progression, improved cardiac function and significantly improved survival.

BackgroundFerric citrate, an iron-based phosphate binder, has been shown to improve both hyperphosphatemia and iron deficiency in adult chronic kidney disease patients, but its use in the pediatric dialysis population has not been described.MethodsThis is a retrospective analysis of 11 unselected pediatric dialysis patients who received ferric citrate as a phosphate binder between 2015 and 2017. Time-averaged laboratory values were compared pre- and post-ferric citrate initiation using the Wilcoxon signed-rank test.ResultsThe median age of this cohort was 13years old (range 4-17years old). Five patients were on hemodialysis, and six patients were on peritoneal dialysis. The median duration of ferric citrate therapy was 214days (range 39-654days), with a median time-averaged ferric citrate dose of 3.5 tablets per day (range 1.5-8.4 tablets per day). Compared to the pre-ferric citrate period, ferric citrate treatment was associated with decreased serum phosphate (6.5 to 5.2mg/dl, p = 0.014), decreased phosphate age-related standard deviation score (SDS) (2.3 to 0.9, p = 0.019), increased transferrin saturation (26 to 34%, p = 0.049), increased ferritin (107 to 230ng/ml, p = 0.074), and maintenance of hematocrit.ConclusionsIn pediatric dialysis patients, ferric citrate may be able to concurrently lower phosphate levels and treat iron deficiency. However, larger studies are needed to further evaluate safety and efficacy in the pediatric chronic kidney disease population.

Chronic kidney disease in the later stages poses many treatment challenges. Hyperphosphatemia is one that is well-known and is often linked to increased cardiovascular morbidity/mortality. Currently, a number of phosphate binders are available that act to conserve serum phosphate at normal or near normal levels. However, it is the overall profile of all binders that needs to be taken into account and the risks and the potential benefits associated with each agent must be balanced when selecting a particular phosphate binder. It is known that calcium-based binders, although effective phosphate binders, may lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. One, new non-calcium phosphate binder, recently approved in Europe, is colestilan. Colestilan possesses a range of properties that may afford further advantages over simply reducing serum phosphate. This review assesses the pharmacology and clinical data of colestilan used to treat hyperphosphatemia in chronic kidney disease stage 5 patients on dialysis. The article was written based on literature searches using PubMed to find articles published on phosphate binders or colestilan over the last 10 years.

Background: Chronic kidney disease (CKD) is a life-threatening disease with numerous complications. Hemodialysis (HD) patients are prone to magnesium deficiency due to malnutrition, which can cause cardiovascular complications and increase mortality. The present study aimed to investigate the effects of sevelamer and calcium carbonate, as phosphate binders, on serum levels of magnesium, calcium, and phosphorus in HD patients. Methods: A parallel clinical trial was conducted on 54 patients undergoing HD at Kosar Hospital of Semnan. The inclusion criteria were end-stage renal disease (ESRD), alternative HD treatment for at least 3 months 3 times a week, and serum phosphate levels greater than 4.5 mg/dL. The participants were randomly assigned to two groups of sevelamer (n = 27) and calcium carbonate (n = 27). If the participants were taking a phosphate binder, they were asked to stop it for 3 weeks. Participants in the sevelamer group received 800 mg of sevelamer at most three times a day and those in the calcium carbonate group were treated with 500 mg of calcium carbonate at most 3 times a day. Before and 3 months after the intervention, the serum levels of calcium, magnesium, and phosphorus were measured through the Arsenazo method using the Pars Azmun kit in the Selectra auto-analyzer. Twenty-one patients in the sevelamer group and 22 patients in the calcium carbonate group finished the study. Results: The results showed that calcium carbonate and sevelamer increased serum magnesium level by 0.20 (P = 0.028) and 0.26 (P = 0.002), on average, which were statistically significant. The administration of calcium carbonate did not significantly change serum calcium levels (P = 0.53), whereas sevelamer reduced serum calcium levels by 0.23 (P = 0.017), on average. This reduction was statistically significant. The results also indicated that none of the calcium carbonate (P = 0.099) and sevelamer (P = 0.543) caused significant changes in serum phosphorus levels. The study findings showed no significant difference between the two groups in terms of changes in the serum levels of magnesium (0.590), calcium (0.116), and phosphorus (0.113). Conclusions: Both drugs (Sevelamer and calcium carbonate) prevented hypomagnesemia and increased serum magnesium levels, but no significant differences were found in blood levels of calcium, phosphorus, and magnesium compared to the two drugs. Considering the effect of magnesium on cardiovascular diseases, increasing the serum magnesium levels through the administration of calcium carbonate and sevelamer can prevent the likelihood of cardiovascular diseases. However, none of the studied drugs was superior to the other in this regard.

Introduction: Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. Methods: We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. Findings: There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. Discussion: Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence.

Introduction: Control of serum phosphate is important for patients on hemodialysis. The aim of the study was to determine if education based on phosphorus-reducing techniques in food preparation and thermal processing, and accordingly prepared and applied diets, will lead to better outcomes than a standard education program to improve phosphate control in patients on hemodialysis. Methods: Forty-seven patients on hemodialysis were divided between an intervention and a control group. All subjects received training about nutrition for hemodialysis patients by trained dietitian. In addition, subjects in the intervention group received additional training in phosphorus-reducing techniques in food preparation and received two hospital meals prepared using suggested cooking methods to reduce the phosphate content of food during dialysis treatment. Serum phosphate, serum albumin, and anthropometric parameters were measured, while nPCR was calculated, at the baseline and during the 1-year study. Findings: No differences in serum phosphate levels were observed between intervention (1.68 mmol/L [1.48–2.03]) and control group (1.88 mmol/L [1.57–2.2]) at baseline (P = 0.130). Although not statistically significant between groups the mean reduction was more apparent in the intervention group (−0.3 mmol/L (−0.4 to 0.1) vs. −0.2 (−0.5 to 0.1)), and lead to significantly reduction of phosphate binder therapy. During the study, the nPCR and anthropometric status of the patients did not change significantly. Discussion: Providing additional education to hemodialysis patients on the specific cooking methods and accordingly prepared meals may decrease serum phosphate levels without significantly affecting nutritional status which may be useful in helping to prevent and treat hyperphosphatemia.

Background Calcium (Ca)-based phosphate (P) binders, compared to non-Ca-based P binders, contribute to vascular calcification, which is associated with cardiovascular events. Methods The LANDMARK study is a multicenter, randomized, open-label, parallel comparative study of lanthanum carbonate (LC) and calcium carbonate (CC) in hemodialysis patients. Stable hemodialysis patients with intact parathyroid hormone ≤240 pg/mL meeting ≥1 of the following criteria (age >65 years, postmenopause, diabetes mellitus) were randomized into the LC and CC groups. LC group patients initially received LC 750 mg/day or the previously used dose and were titrated up to a maximum 2250 mg/day to achieve serum P levels of 3.5–6.0 mg/dL. CC group patients received CC 3 g/day or the previously used dose and were titrated to achieve the same P range. If the target serum P level was not achieved, non-Ca-based P binders (other than LC) could also be added. The primary endpoint is survival time free of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction or stroke, and unstable angina. Results Overall, 2309 patients were allocated to the LC (N = 1154) or CC group (N = 1155). At baseline, the mean age was 68.4 years, 40.4 % were women, 55.9 % had diabetes, 18.3 % had a history of ischemic heart disease, and 13.9 % had cerebrovascular disease. A total of 184 patients (8.4 %) had undergone coronary intervention procedures. Baseline characteristics were well balanced between groups. Conclusions The LANDMARK study will determine whether LC, a non-Ca-based P binder, reduces cardiovascular mortality and morbidity in chronic hemodialysis patients.

Background and purpose Phosphate imbalance is often present in chronic kidney disease (CKD), and it contributes to a higher cardiovascular mortality rate. A phosphate binder is typically part of a treatment strategy for controlling phosphate imbalance. However, safety concerns and low compliance are two well-recognized disadvantages of on-market phosphate binders. This report describes the preclinical studies of VS-505, a non-absorbable, calcium- and aluminum-free, plant-derived polymer currently being evaluated in haemodialysis patients in Australia. Experimental approach Normal Sprague Dawley (SD) rats or uraemic SD rats induced by 5/6 nephrectomy fed a high-phosphate diet were treated with VS-505 or sevelamer (0.05-10% in food) for 5 and 28 days respectively. Key results Urinary and serum phosphate levels were significantly elevated in untreated rats, and were decreased by VS-505 and sevelamer. VS-505 increased faecal phosphate levels in a dose-dependent manner. High-phosphate diet also caused an increase in serum FGF-23 and parathyroid hormone in nephrectomized (NX) rats, effects prevented by VS-505 or sevelamer. Significant aortic calcification was observed in NX rats treated with 5% sevelamer, whereas VS-505 at all doses tested did not show effects. VS-505 had no effects on small intestine histomorphology and intestinal sodium-dependent phosphate cotransporter gene expression. In vitro characterizations showed that VS-505 has a relatively high density and low expansion volume when exposed to simulated gastric fluid. Conclusions and implications VS-505 is a safe and effective phosphate binder and may offer the advantage of having a reduced pill burden and minimal GI side effects for CKD patients.

Serum Mg levels are elevated in patients with renal insufficiency: harmful effects of hypomagnesemia have been reported in patients receiving hemodialysis (HD). In this cross-sectional study, which included 86 HD patients (male : female = 56:30, age 68 ± 12 years), we examined the clinical factors associated with serum Mg levels, with a focus on sevelamer, a phosphate binder widely used to control the hyperphosphatemia of HD patients. The mean serum Mg concentration among our patients was 2.48 ± 0.37 mg/dL (1.02 ± 0.15 mmol/L). Sevelamer was administered to 67 patients (77.9%) at a mean dose of 1.98 ± 1.64 g/day. Sex, diabetes mellitus, cardiovascular disease, anuria, and drugs other than sevelamer were not associated with serum Mg levels. HD duration, serum calcium, albumin, high-density lipoprotein cholesterol, normalized protein catabolic rate (nPCR), creatinine generation rate, and sevelamer dose correlated positively with serum Mg levels, whereas a negative correlation was observed for age and high-sensitivity C-reactive protein. A stepwise multiple regression analysis revealed that age, nPCR, and the dose of sevelamer were independently associated with serum Mg levels. Sevelamer and Mg have been reported to exhibit similar effects, such as an anti-inflammatory effect, inhibition of cardiovascular calcification, and decreased mortality. Therefore, the pleiotropic effects of sevelamer may be partly attributable to the increase in serum Mg levels caused by the drug itself.

Background In-centre nocturnal hemodialysis (INHD, 7-8 hours/session, 3 times/week) is an increasingly utilized form of dialysis intensification, though data on the cardiovascular benefits of this modality are limited. Methods In this prospective cohort study, we enrolled 67 prevalent conventional hemodialysis (CHD, 4 hours/session, 3 times/week) recipients at 2 medical centres in Canada, of whom 37 converted to INHD and 30 remained on CHD. The primary outcome was the change in left ventricular mass (LVM) after 1 year as assessed by cardiac magnetic resonance imaging. Secondary outcomes included changes in serum phosphate concentration, phosphate binder burden, haemoglobin, erythropoiesis stimulating agent usage, and blood pressure. Results Conversion to INHD was associated with a 14.2 (95% confidence interval [CI] 1.2-27.2) g reduction in LVM as compared with continuation on CHD. This result was maintained after adjustment for baseline imbalances between the groups and in ancillary analyses. There was a trend toward a larger drop in systolic blood pressure (9.8 [95% CI, −1.4-20.9] mm Hg) among INHD recipients with a significant reduction in the number of prescribed antihypertensive agents (0.7 [95% CI, 0.3-1.1] agents). Serum phosphate declined by 0.40 (95% CI, 0.16-0.63) mmol/L among INHD recipients without any difference in calcium-based phosphate binder requirements, as compared with those who remained on CHD. Conclusions Compared with continuation of CHD, conversion to INHD was associated with significant LVM regression and reduction in serum phosphate concentration at 1 year.

In hemodialysis patients, mineral and bone disorder is an important risk factor for cardiovascular disease and subsequent death through the progression of vascular calcification. Serum phosphorus plays a major role in this process. In the present study, we retrospectively analyzed the effects of oral phosphate binder, lanthanum carbonate (LC), on the mortality in hemodialysis patients. Among a total of 841 patients who underwent maintenance hemodialysis on 1 July 2010, patients who were treated with LC (LC group, N = 324) and those who were treated without LC (NLC group, N = 517) were compared with respect to their all-cause mortality for a long-term observation period of up to 36 months. The mortality rate was compared using the Cox proportional hazard model adjusted by the propensity score. The adjusted hazard ratio for mortality in the LC group versus NLC group was 0.515 (95% confidence interval, 0.328-0.807), suggesting that the use of LC is associated with an almost 50% reduction in the mortality rate. The present retrospective study including all hemodialysis patients demonstrated, for the first time, an association between the use of LC and improved prognosis in hemodialysis patients. Randomized controlled trials should be done in the future to validate our present findings.