Dialysate calcium and calcium/phosphate balance in hemodialysis

The changing pattern of pharmaceutical use in dialysis patients has resulted in several alterations to dialysate calcium concentration over the past 40 years. Non‐calcium–containing phosphate binders and calcimimetics are the most recent examples of drugs that influence the overall calcium balance in dialysis patients. Renal osteodystrophy, vascular disease, and mortality are believed to be linked in patients with chronic kidney disease (CKD), although to date most of the evidence is based only on statistical associations. The precise pathophysiology of vascular calcification in end‐stage renal disease is unknown, but risk factors include age, hypertension, time on dialysis, and, most significantly, abnormalities in calcium and phosphate balance. Prospective studies are required before “cause and effect” can be established with certainty, but it is an active metabolic process with inhibitors and promoters. Serum calcium levels are clearly influenced by dialysate calcium and may therefore play an important role in influencing vascular calcification. Clinical management of hyperphosphatemia is being made easier by the introduction of potent non‐calcium–based oral phosphate binders such as lanthanum carbonate. Short‐term and long‐term studies have demonstrated its efficacy and safety. Vitamin D analogs have been a disappointment in the control of serum parathyroid hormone (PTH) levels, but evidence is emerging that vitamin D has other important metabolic effects apart from this, and may confer survival advantages to patients with CKD. Calcimimetics such as cinacalcet enable much more effective and precise control of PTH levels, but at the cost of a major financial burden. While it is unreasonable to expect that any one of these recent pharmacological developments will be a panacea, they provide researchers with the tools to begin to examine the complex interplay between calcium, phosphate, vitamin D, and PTH, such that further progress is fortunately inevitable.     

How Degradation of Calcium Phosphate Bone Substitute Materials is influenced by Phase Composition and Porosity

The chemical composition of calcium phosphate (CaP) materials for the regenerative therapy of large bone defects is similar to that of bone. Additionally, calcium phosphates show an excellent biocompatibility. Besides the support of defect healing calcium phosphate implants should be completely degraded within an adequate time period to be replaced by newly formed bone. Although degradation of CaP‐implants occurs mainly by dissolution of the material, it is important to characterize the osteoclastic resorption as well, which is involved in native bone remodeling. The degradation of bone substitutes made of calcium phosphate ceramics is influenced by various parameters, such as defect size and localization, the general health situation, and age of the patient, but also material properties are important. Especially, the calcium phosphate composition is crucial for the degradation behavior of a calcium phosphate material. Additionally, at the cellular level the micro‐ and macroporosity, including interconnecting pores, influences both, the dissolution and the osteoclastic resorption. In our study, three different calcium phosphate materials (hydroxyapatite, tricalcium phosphate, and a biphasic calcium phosphate) and two different geometries (dense 2D samples and porous 3D scaffolds) are compared regarding their dissolution and resorption behavior. The results show, that the dissolution of CaP‐ceramics, as examined by the incubation in a degradation solution, depends mainly on the calcium phosphate phase but also on the porosity of the implant. Regarding the resorption, cell proliferation and differentiation of a monocytic cell line as well as the formation of resorption lacunas are analyzed. Cell proliferation is comparable on all phase compositions. Cell differentiation and resorption, however, are influenced by the calcium phosphate phase composition and by the implant porosity as well. By understanding these two mechanisms of degradation, bone substitute materials and, as a result, the bone regeneration of large bone defects using CaP‐ceramics can be improved.     

Cervical tumoral calcinosis with secondary hyperparathyroidism in a chronic hemodialysis patient

Tumoral calcinosis is an uncommon and severe complication of chronic renal failure. It is generally associated with the presence of a high‐serum calcium‐and‐phosphorus product. We report here a case of a patient on maintenance hemodialysis who presented with progressively increasing, solitary, tumor‐like swelling over the nape of the neck. A 50‐year‐old female on thrice weekly maintenance hemodialysis for the last 3 years presented with a small swelling over the nape of the neck that had been progressively increasing over the last 1 year to cricket ball size. The patient was investigated and diagnosed as having tumoral calcinosis. The metastatic calcification occurring in the patient was most likely related to high calcium × phosphate product with coexistent secondary hyperparathyroidism possibly aggravated by vitamin D therapy. The patient was treated with withdrawal of vitamin D therapy, strict control of serum phosphate levels with noncalcemic phosphate binders, and subtotal parathyroidectomy. The neck swelling started decreasing in size after 2 months of parathyroidectomy and there was marked clinical improvement with drop in serum parathormone levels, over a period of 6 months. After 2 years of parathyroidectomy, the neck swelling again started increasing in size with increase in serum parathormone levels. The patient was treated with cinacalcet and the neck swelling gradually decreased in size along with control of serum parathormone and phosphate levels.     

Mg<Superscript>2+</Superscript> substituted calcium phosphate nano particles synthesis for non viral gene delivery application

Gene therapy provides a unique approach to medicine as it can be adapted towards the treatment of both inherited and acquired diseases. Recently, calcium phosphate vectors as a new generation of the non viral gene delivery nano carriers have been studied because of their biocompatibility and DNA condensation and gene transfer ability. Substituting cations, like magnesium, affects physical and chemical properties of calcium phosphate nano particles. In this study, Mg²⁺ substituted calcium phosphate nano particles have been prepared using the simple sol gel method. X-ray diffraction analysis, Fourier transform infra red spectroscopy, transmission electron microscopy, specific surface area analysis, zeta potential measurement and ion release evaluation were used for characterization of the samples. It was concluded that presence of Mg ions decrease particle size and crystallinity of the samples and increase positive surface charge as well as beta tricalcium phosphate fraction in chemical composition of calcium phosphate. These properties result in increasing the DNA condensation ability, specific surface area and dissolution rate of the samples which make them suitable particles for gene delivery application.     

NiTi shape memory alloys coated with calcium phosphate by plasma‐spraying. Chemical and biological properties

Plates of superelastic nickel‐titanium shape memory alloy (NiTi) were coated with calcium phosphate (hydroxyapatite) by high‐temperature plasma‐spraying. The porous layer of about 100 μm thickness showed a good adhesion to the metallic substrate that withstood bending of the plate but detached upon cutting the plate. The biocompatibility was tested by cultivation of blood cells (whole blood and isolated granulocytes [a subpopulation of blood leukocytes]). As substrates, pure NiTi, plasma‐spray‐coated NiTi and calcium phosphate‐coated NiTi prepared by a dip‐coating process were used. The adhesion of whole blood cells to all materials was not significantly different. In contrast, isolated granulocytes showed an increased adhesion to both calcium phosphate‐coated NiTi samples. However, compared to non‐coated NiTi or dip‐coated NiTi, the number of dead granulocytes adherent to plasma‐sprayed surfaces was significantly increased for isolated granulocytes (p<0.01).     

Physicochemical properties and release characteristics of growth factor‐modified calcium phosphate bone cement

The addition of growth factors, such as recombinant human transforming growth factor‐β1 (rhTGF‐β1) to calcium phosphate cements (CPCs) may improve bone regeneration. Previously we have shown that the differentiation of pre‐osteoblastic cells from adult rat long bones was stimulated by rhTGF‐β1 in CPC. CPC that was intermixed with rhTGF‐β1 and then applied in rat calvarial defects enhanced bone growth around the cement and increased the degradation of the cement. It is still unknown however whether the addition of rhTGF‐β1 changes the material properties of the CPC, and what the release characteristics are of rhTGF‐β1 from the CPC. We therefore determined here the release of rhTGF‐β1 in vitro from the cement pellets as implanted in the rat calvariae. The possible intervening effects of rhTGF‐β1‐intermixing on clinical compliance of CPC were studied by assessing its compressive strength and setting time, as well as crystallinity, calcium to phosphorus ratio, porosity and microscopic structure. CPC was prepared by mixing calcium phosphate powder (58% α‐tricalcium‐phosphate, 25% dicalcium‐phosphate anhydrous, 8.5% calcium‐carbonate and 8.5% hydroxyapatite), with liquid (3 g/ml). The liquid for standard CPC consisted of water with 4% sodium hydrogen phosphate, while the liquid for modified CPC, was mixed with an equal amount of 4 mM hydrochloride with 0.2% bovine serum albumin. The hydrochloride liquid contained the rhTGF‐β1 in different concentrations for the release experiments. Most of the incorporated rhTGF‐β1 in the cement pellets was released within the first 48 hr. Approximately 0.5% rhTGF‐β1 (intermixed at 100 ng to 2.5 mg/g CPC) was released within the first 4 hr increasing to 1% after 48 hr. rhTGF‐β1 release continued at 0.1% up to at least 8 weeks. Modification of CPC slightly increased the initial setting time at 20°C from 2.6 to 5 min, but did not affect the final setting time of the CPC at 20°C, nor the initial and final setting time at 37°C. The compressive strength was increased from 18 MPa (standard CPC) to 28 MPa (modified CPC) only at 4 hr after mixing. The compressive strength diminished in the modified CPC between 24 hr and 8 weeks from 55 to 25 MPa. X‐ray diffraction revealed that both standard and modified CPC changed similarly from the basic components, alpha‐tri‐calcium phosphate and dicalcium phosphate anhydrous, into an apatite cement. The calcium to phosphorus ratio as determined by an electron microprobe did not differ for standard CPC and modified CPC. Standard and modified CPC became a dense and homogeneous structure after 24 hr, but the modified CPC contained more crystal plaques compared to the standard CPC, as observed by scanning electron microscopy (SEM). SEM and back scattered electron images revealed that after 8 weeks both cements showed an equally and uniform dense structure with microscopic pores (less than 1 μm). Both CPCs showed fewer crystal plaques at 8 weeks than at 24 hr. This study shows that the calcium phosphate cement was not severely changed by modification of the CPC for rhTGF‐β1. Clinical handling may be affected by the prolonged setting time of modified cement, but it is still within preferable limits. Compressive strength was for both standard and modified cements within the range of thin trabecular bone, and therefore both CPCs can withstand equal mechanical loading. The faster diminishing compressive strength of modified cement (from 24 hr to 8 weeks) likely results in early breakdown, and therefore might be favourable for bone regeneration. Together with our previous studies showing the beneficial effects of adding rhTGF‐β1 to CPC on bone regeneration, we conclude that the envisaged applications for CPC in bone defects are upgraded by intermixing of rhTGF‐β1. Therefore the combination of CPC with rhTGF‐β1 forms a promising synthetic bone graft.     

Association of coronary artery calcium score and vascular dysfunction in long‐term hemodialysis patients

Long‐term hemodialysis patients are prone to an exceptionally high burden of cardiovascular disease and mortality. The novel temperature‐based technology of digital thermal monitoring (DTM) of vascular reactivity appears associated with the severity of coronary artery disease in asymptomatic population. We hypothesized that in hemodialysis patients, the DTM and coronary artery calcium (CAC) score have a gradient association that follows that of subjects without kidney disease. We examined the cross‐sectional DTM‐CAC associations in a group of long‐term hemodialysis patients, and their 1:1 matched normal counterpart. Area under the curve for temperature (TMP‐AUC), the surrogate of the DTM index of vascular function, was assessed after a 5‐minute arm‐cuff reactive hyperemia test. Coronary calcium score was measured via electron beam computed tomography or multidetector computed tomography scan. We studied 105 randomly recruited hemodialysis patients (age: 58 ± 13 years, 47% men) and 105 age‐ and gender‐matched controls. In hemodialysis patients vs. controls, TMP‐AUC was significantly worse (114 ± 72 vs. 143 ± 80, P = 0.001) and CAC score was higher (525 ± 425 vs. 240 ± 332, P < 0.001). Hemodialysis patients were 14 times more likely to have CAC score >1000 as compared with controls. After adjustment for known confounders, the relative risk for case vs. control for each standard deviation decrease in TMP‐AUC was 1.46 (95% confidence interval: 1.12–1.93, P = 0.007). Vascular reactivity measured via the novel DTM technology is incrementally worse across CAC scores in hemodialysis patients, in whom both measures are even worse than their age‐ and gender‐matched controls. The DTM technology may offer a convenient and radiation‐free approach to risk‐stratify hemodialysis patients.     

Rationale and study design of a three‐period, 58‐week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis

Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end‐stage renal disease. One of the cornerstones of treatment is the use of phosphate‐binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three‐period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2‐week washout period, a 52‐week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4‐week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end‐stage renal disease patients who have been treated with thrice‐weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three‐period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.     

Effect of incident nocturnal home hemodialysis versus incident continuous ambulatory peritoneal dialysis on employment rate,clinical, and laboratory outcomes: A 1‐year retrospective observation study

Introduction: While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed. Methods: A 1‐year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin). Findings: NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age‐adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77–20.99, P = 0.04). They consumed less aluminum‐based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol²/L², P < 0.01), with similar hemoglobin levels. Discussion: NHHD appeared to offer higher employment rate, lower dosage of aluminum‐based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong.     

Guided Assembly of Microporous/Mesoporous Manganese Phosphates by Bifunctional Organophosphonic Acid Etching and Templating

Manganese (Mn)‐based compounds are important materials for both energy conversion and energy storage. Unfortunately, it has been a significant challenge to develop highly ordered microporous/mesoporous structures for them to provide more active sites for these applications. In order to do so using the soft‐templating method, three conditions have to be met, namely, a strong interaction between the inorganic precursor and the organic templates; eliminating the formation of bulk manganese phosphate; and the preservation of the manganese phosphate framework without it collapsing upon template removal. Herein, a soft‐templating approach is reported using an organophosphonic acid (n‐hexylphosphonic acid) as both the etching and the templating agent, followed by high‐vacuum‐assisted annealing. This approach simultaneously satisfies the above conditions. Both microporous and mesoporous manganese phosphates with uniform pore sizes and well‐defined pore structures are obtained. The utilization of the organophosphonic acid is shown to be the key in the transformation from bulk manganese oxide into a highly ordered microporous phosphate. A very high surface area of 304.1 m² g^?1 is obtained for the microporous manganese phosphate, which is the highest among the reported values for Mn‐based compounds. The ultrafine micropores and high specific surface area of our manganese phosphate promote electrocatalytic activity for the oxygen evolution reaction.     

The role of prenucleation clusters in surface-induced calcium phosphate crystallization

Unravelling the processes of calcium phosphate formation is important in our understanding of both bone and tooth formation, and also of pathological mineralization, for example in cardiovascular disease. Serum is a metastable solution from which calcium phosphate precipitates in the presence of calcifiable templates such as collagen, elastin and cell debris. A pathological deficiency of inhibitors leads to the uncontrolled deposition of calcium phosphate. In bone and teeth the formation of apatite crystals is preceded by an amorphous calcium phosphate (ACP) precursor phase. ACP formation is thought to proceed through prenucleation clusters--stable clusters that are present in solution already before nucleation--as was recently demonstrated for CaCO(3) (refs 15,16). However, the role of such nanometre-sized clusters as building blocks for ACP has been debated for many years. Here we demonstrate that the surface-induced formation of apatite from simulated body fluid starts with the aggregation of prenucleation clusters leading to the nucleation of ACP before the development of oriented apatite crystals.     

Eine innovativ im Sol‐Gel‐Prozeß hergestellte,hochporöse Siliziumoxidkeramik zum Knochenersatz – In‐vivo Langzeitergebnisse

A new high porous silica‐sol‐gel‐ceramics for bone grafting – in‐vivo long‐time investigations The new calcium phosphate ceramics was produced by a sol‐gel‐process at 200 °Celsius with silica (SiO₂) as adjuvant. The aim of this investigation was to test the osteoinductive effect of these bioceramics and to prove its biodegradation by means of animal experiments. One year old minipigs were used and divided into three groups (n=6). Critical size defects (>5cm³) in the mandible were filled by different materials (group1: 60 % hydroxilapatite [HA] + 40 % ß‐tricalciumphosphate, group 2: only HA; group 3: control, without ceramics). Eight months later clinical, histological, morphometrical and REM investigations concerning the state of former defected mandible were made. In groups 1 and 2 a complete reossification of the bone defects and a biodegradation rate of ceramics of more than 96 % were recognized. In conclusion silica‐calcium phosphate ceramics made by a sol gel method seems to be suitable for filling bone defects in men and is of interest for orthopedic surgery, traumatology, craniomaxillofacial surgery and dentistry. Recently a clinical study was started.     

In‐vitro preparation of nanocrystalline calcium phosphates as bone substitution materials in surgery

A continuous preparation method for nanoscopic calcium phosphate ceramics is presented. The influence of processing parameters (temperature, time) on the properties of calcium phosphates was studied. Crystallinity, structure, and morphology are important for an application as biodegradable implant material in bone contact. The samples were studied in detail using X‐ray powder diffraction, infrared spectroscopy, atomic absorption spectroscopy, photometry, scanning electron microscopy, and transmission electron microscopy. All calcium phosphate precipitates are non‐stoichiometric, calcium‐deficient hydroxyapatites.     

Assessment of intradialysis calcium mass balance by a single pool variable‐volume calcium kinetic model

Introduction: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single‐pool variable‐volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. Methods: Thirty‐four patients on thrice‐weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end‐dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. Findings: The difference between predicted and measured values was 0.02 mmol/L (range ?0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD ?0.84 ± 1.33 mmol, range ?5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. Discussion: The proposed single pool variable‐volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.     

Linking Centers for Medicare & Medicaid Services data with prospective DCOR trial data: Methods and data comparison results

The Dialysis Clinical Outcomes Revisited (DCOR) trial was a large randomized, multicenter 3‐year trial comparing the effects of sevelamer with calcium‐based binders on mortality, hospitalization, morbidity, and medical costs in hemodialysis subjects. Dialysis Clinical Outcomes Revisited was prospectively designed to link subjects to the Centers for Medicare & Medicaid Services End‐Stage Renal Disease (CMS ESRD) database to collect additional baseline characteristic data and to enhance outcome evaluation. Subjects were linked to the CMS ESRD database by means of an algorithm using several patient identifiers. Some baseline characteristic data were collected exclusively from the CMS ESRD database. Mortality and hospitalization end points were obtained from the CMS ESRD database and compared with similar data collected prospectively into a case‐report form (CRF) database. Of the 2103 patients who participated in the DCOR study, 2101 were successfully linked to the CMS ESRD database. Patient baseline data showed that treatment groups were well‐balanced, except that a higher proportion of subjects in the calcium‐based binder group had atherosclerotic heart disease. Calculated mortality rates were similar between databases, but more deaths were identified in the CMS than in the CRF database. These additional deaths were verified through several sources. More hospitalizations were also detected in the CMS than in the CRF database. The CMS database was a good source of death end points and hospitalization occurrence. Linking patients to the data‐rich CMS ESRD database allowed assessment of additional important secondary end points at a relatively low cost compared with prospective data collection.     

Development of a new calcium phosphate powder-binder system for the 3D printing of patient specific implants

A key requirement for three-dimensional printing (3-DP) of medical implants is the availability of printable and biocompatible powder-binder systems. In this study we developed a powder mixture comprising tetracalcium phosphate (TTCP) as reactive component and β-tricalcium phosphate (β-TCP) or calcium sulfate as biodegradable fillers, which can be printed with an aqueous citric acid solution. The potential of this material combination was demonstrated printing various devices with intersecting channels and filigree structures. Two post-processing procedures, a sintering and a polymer infiltration process were established to substantially improve the mechanical properties of the printed devices. Preliminary examinations on relevant application properties including in vitro cytocompatibility testing indicate that the new powder-binder system represents an efficient approach to patient specific ceramic bone substitutes and scaffolds for bone tissue engineering.     

The roles of magnesium in the mineral metabolism of biological apatite for the treatment of arthritis inspired by the deer antler

Nowadays, the treatment of osteoarthritis (OA), a highly prevalent joint disorder, remains a medical challenge because of the lack of understanding of its pathogenesis. In this work, we developed an alternative strategy of OA treatment using magnesium-based materials as potential therapeutic agent towards subchondral bone remodeling. We selected deer antlers as the animal model where calcification behaviors could provide interesting references for the rapid and reproducible endochondral bone growth. Extremely high content of Mg was detected in the antler, which was able to affect the evolutions of biological apatite. Herein, octacalcium phosphate (OCP) and amorphous calcium phosphate (ACP), which are critically involved in the calcification process, were respectively synthesized under the Mg-containing conditions to understand the role of Mg in the evolution of biological apatite. Results showed that the substitution of Mg²⁺ at lower contents stabilized OCP and ACP, while higher contents of Mg inhibited the formation of both phases. The size of both calcium phosphates was also altered significantly by the addition of Mg. The results of cell culture indicated that excess Mg notably accelerated the secretion of extracellular matrix and inhibited the mineralization of chondrocyte matrix. Hence, utilization of Mg-based materials in subchondral bone was supposed to provide a potential therapeutic approach to treat the OA by inhibiting subchondral of ossification process.     

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis

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.     

磷酸钙涂覆炭织物体外细胞毒性的评价

医用植人体的成功与否常常取决于器件植入后细胞与材料表面间的相互作用.采用生物体外测试法考察了声电化学法制备的磷酸钙涂层对炭织物的骨细胞附着、增殖能力的影响.借助MTS检测技术、扫描电子显微镜,选择人类成骨细胞(MG63)作为细胞模型,通过测定细胞与炭织物、磷酸钙涂覆炭织物、以及其各自的提取液作用后的存活能力,研究了细胞/材料的相互作用,并对基底材料的细胞毒性进行了评价.结果表明,炭织物、磷酸钙涂覆炭织物均不具有细胞毒性,且磷酸钙涂层可提高成骨细胞的附着和增殖.SEM图像显示,细胞形貌正常,与对照组相比较生长增殖情况相似.