Bixalomer in Hyperphosphatemic Patients With Chronic Kidney Disease Not on Dialysis: Phase 3 Randomized Trial

Currently, calcium‐ or metal‐containing phosphate binders are available to treat hyperphosphatemia in predialysis patients with chronic kidney disease. Bixalomer, a non‐calcium, metal‐free phosphate binder, has not been studied in these patients. We evaluated the efficacy and safety of bixalomer versus placebo for treatment of hyperphosphatemia in Japanese predialysis patients with chronic kidney disease. This multicenter, randomized, double‐blind, phase 3 trial, randomized eligible patients 1:1 to receive bixalomer or placebo for 12 weeks. Bixalomer was started at 1500 mg/day and adjusted up to 7500 mg/day depending on serum phosphorus concentrations. The primary endpoint was change in serum phosphorus concentration from baseline to end of treatment. After a 4‐week pre‐investigational period, 163 patients (bixalomer: N = 81; placebo: N = 82) were randomized. The adjusted mean change (95% confidence interval) from baseline to end of treatment in serum phosphorus was significantly greater with bixalomer (–0.78 [–0.98, –0.57] mg/dL) versus placebo (0.20 [–0.00, 0.41] mg/dL); mean difference: –0.98 (–1.27, –0.69), P < 0.001. At end of treatment, 57.5% of bixalomer‐treated patients achieved target serum phosphorus concentrations, mean serum intact parathyroid hormone and fibroblast growth factor‐23 decreased, and there were no significant changes in corrected serum calcium. The safety and tolerability of bixalomer was similar to placebo. The most common drug‐related adverse events were gastrointestinal (>24% patients per group). There was a significant increase in bicarbonate concentrations with bixalomer versus placebo (P = 0.003). Bixalomer was superior to placebo for hyperphosphatemia in Japanese predialysis patients with chronic kidney disease and may constitute a new treatment option.     

New Method for the Approximation of Corrected Calcium Concentrations in Chronic Kidney Disease Patients

The following conventional calcium correction formula (Payne) is broadly applied for serum calcium estimation: corrected total calcium (TCa) (mg/dL) = TCa (mg/dL) + (4 – albumin (g/dL)); however, it is inapplicable to chronic kidney disease (CKD) patients. A total of 2503 venous samples were collected from 942 all‐stage CKD patients, and levels of TCa (mg/dL), ionized calcium ([iCa²⁺] mmol/L), phosphate (mg/dL), albumin (g/dL), and pH, and other clinical parameters were measured. We assumed corrected TCa (the gold standard) to be equal to eight times the iCa²⁺ value (measured corrected TCa). Then, we performed stepwise multiple linear regression analysis by using the clinical parameters and derived a simple formula for corrected TCa approximation. The following formula was devised from multiple linear regression analysis: Approximated  corrected TCa (mg/dL) = TCa + 0.25 × (4 ? albumin) + 4 × (7.4 ? p H) + 0.1 × (6 ? phosphate) + 0.3. Receiver operating characteristic curves analysis illustrated that area under the curve of approximated corrected TCa for detection of measured corrected TCa ≥ 8.4 mg/dL and ≤ 10.4 mg/dL were 0.994 and 0.919, respectively. The intraclass correlation coefficient demonstrated superior agreement using this new formula compared to other formulas (new formula: 0.826, Payne: 0.537, Jain: 0.312, Portale: 0.582, Ferrari: 0.362). In CKD patients, TCa correction should include not only albumin but also pH and phosphate. The approximated corrected TCa from this formula demonstrates superior agreement with the measured corrected TCa in comparison to other formulas.     

磷酸酯单体PENTA与牙科氧化锆陶瓷结合的化学证据

目的 提供磷酸酯单体双季戊四醇五丙烯酸酯磷酸酯（Dipentaerythritol penta-acrylate phosphate,PENTA）与牙科氧化锆陶瓷结合的化学证据,分析PENTA提高牙科氧化锆陶瓷粘接的机理。 方法 配置包含PENTA的质量分数为5%、10%、15%、20%的实验性底涂剂,用其处理Y-TZP（Yttria-stabilized tetragonal zirconia polycrystals）瓷粉,随后以丙酮反复清洗去除游离成分后分别进行红外光谱分析（fourier transform infrared spectroscopy,FTIR）和热重分析（thermogravimetric analysis,TG）。FTIR分析以10%PENTA丙酮溶液作为对照,分别采用二阶导数分峰和残差分峰两种方法对FTIR图谱磷酸基团特征峰进行分峰分析;TG以空白Y-TZP粉作为对照。 结果 两种FTIR分峰分析结果一致,均表明各种浓度的包含PENTA的底涂剂与Y-TZP陶瓷接触后,磷酸基团的P-O键振动所产生的波峰向波数减小的方向移动。热重结果证明PENTA能够化学吸附于Y-TZP表面,高浓度组的PENTA与氧化锆的反应程度更高。 结论 PENTA能够与Y-TZP发生化学结合,该化学反应的存在依赖于PENTA分子中的磷酸基团发挥作用。     

Lowering vascular calcification burden in chronic kidney disease: Is it possible?

High prevalence of atherosclerosis and arterial calcification in chronic kidney disease is far beyond the explanation by common cardiovascular risk factors such as aging diabetes, hypertension and dyslipidemia. The magnitude of coronary artery calcification is independently and inversely associated with renal function. In addition to cardiovascular risk factors, other chronic kidney disease-related risks such as phosphate retention, excess of calcium and prolonged dialysis vintage also contribute to the development of vascular calcification. Strategies to lower vascular calcification burden in chronic kidney disease population should include minimizing chronic kidney disease and atherosclerotic risk factors. Current therapies available are non-calcium containing phosphate binders, low dose active vitamin D and calcimimetic agent. The role of bisphosphonates in vascular calcification in chronic kidney disease population remains unclear. Preliminary data on sodium thiosulfate are promising, however, larger studies on efficacy and patient outcomes are necessary. Several large randomized controlled trials have confirmed the lack of benefit of statin in attenuating the progression of vascular calcification.     

结核分枝杆菌phoS2基因在大肠埃希菌中的高效表达及其产物抗原性分析

目的在大肠埃希菌中高效表达结核杆菌phoS2,通过免疫印迹反应初步鉴定重组蛋白的抗原性和特异性。方法采用DNA重组技术构建结核分枝杆菌phoS2抗原表达载体,用双酶切和PCR等方法鉴定转化子,重组质粒转化大肠埃希菌,诱导表达phoS2;用SDS-PAGE初步鉴定其表达量;将表达产物进行纯化;重组蛋白用Western blot分析其抗原性和特异性。结果phoS2基因在大肠埃希菌中得到高效表达,表达量占全菌蛋白的40％以上;重组蛋白与结核病患者血清标本呈强阳性反应,与健康人血清标本呈阴性反应。结论重组phoS2蛋白在大肠埃希菌中主要以包涵体形式表达,有很好的抗原特异性和免疫原性,对结核病诊断有潜在的应用价值。     

Bone mineral content and mineral metabolism during cyclosporine treatment of nephrotic Syndrome

OBJECTIVE: Although cyclosporine (Cy) has been associated with bone loss following transplantation, its effects on bone in growing children are largely unknown. STUDY DESIGN: Thirty-seven patients (2-16 years of age) with remitting nephrotic syndrome (NS), n = 16 receiving Cy for 39 +/- 27 months and n = 21 without Cy, underwent mineral metabolism and bone turnover assessment. In 28 of 37 patients, bone mineral density (BMD) was obtained while off corticosteroid therapy (Rx). RESULTS: Urinary calcium (Ca), phosphate (PO(4)), and magnesium (Mg) excretion was normal, but serum Mg was lower in patients receiving Cy (1.8 +/- 0.1 v 1.95 +/- 0.2 mg/dL, P < .05). BMD Z scores were similar at the spine (-0.45 +/- 0.74 v 0.04 +/- 0.9) and femur (-0.17 +/- 0.52 v 0.38 +/- 1.28) with no Z score <-2. Serum bone-specific alkaline phosphatase was normal, and N-telopeptide of type I collagen also normal, was higher on Cy (P < .05). Cumulative prednisone exposure was similar and had no significant effect on height and BMD Z scores. Length of Cy-Rx and time elapsed from onset of NS did not correlate with BMD, height Z score, or markers of bone turnover. CONCLUSIONS: In growing children with NS, during long-term Cy-Rx urinary wasting of Ca and Mg was absent and bone density was preserved.     

An ultrastructural investigation of tissue-engineered pulp constructs implanted within endodontically treated teeth

BACKGROUND: The authors conducted an ultrastructural scanning electron microscopic (SEM) investigation of tissue-engineered pulp constructs implanted within endodontically treated teeth. METHODS: Stem cells from human exfoliated deciduous teeth were seeded on a synthetic open-cell D,D-L,L-polylactic acid scaffold with or without the addition of bone morphogenic protein-2 and transforming growth factor beta1 to create pulp tissue constructs. The pulp constructs were implanted into 105 extracted human premolar teeth with a single root canal that had been cleaned and shaped by using rotary instrumentation in a crown-down manner to ISO size no. 35. RESULTS: An ultrastructural examination of the SEM micrographs at x2,000 magnification revealed cell adherence within all of the pulp constructs, with little difference between the scaffold types or with the addition of growth factors. CONCLUSIONS: These results support the proof-of-concept that it is possible to implant tissue-engineered pulp constructs into teeth after cleaning and shaping. CLINICAL IMPLICATIONS: Future regenerative endodontic treatment may involve the cleaning and shaping of root canals followed by the implantation of vital dental pulp tissue constructs created in the laboratory.     

Biofilm plaque and hydrodynamic effects on mass transfer, fluoride delivery and caries

BACKGROUND: The biofilm concept of dental plaque now is widely accepted in the dental clinic, particularly with respect to its importance to oral hygiene. A number of reviews have focused on the microbial ecology of biofilm with regard to oral health; however, there has been less focus on how the interaction of biofilms and hydrodynamics with mass transfer (the movement of molecules and particulates) and physiological processes may relate to caries. TYPES OF STUDIES REVIEWED: The authors reviewed reports in the microbiology and dental literature addressing microbiological, engineering and clinical aspects of biofilms with respect to mass transport and microbial physiology, with an emphasis on fluoride ions (F(-)). CONCLUSIONS: and Practical Implications. These data illustrate how dental plaque biofilms may affect the delivery of cariogenic agents, such as sucrose, or anticariogenic agents, such as F(-), into and out of the biofilm, with subsequent consequences for the development of physio-chemical microenvironments at the tooth surface. Increasing the flow rate in an overlying fluid (such as saliva or mouthrinse) increases transport from the fluid into and through biofilms. Increasing the delivery of anticariogenic agents such as F(-) into the plaque biofilm, by generating strong fluid flows, may be a useful strategy for enhancing the anticaries effects of F(-) in areas of the mouth where complete biofilm removal is not possible with routine daily cleaning techniques.