Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan

A prospective, randomized open-label trial of sevelamer hydrochloride with or without calcium carbonate (CC) involved 86 hemodialysis patients in Japan. The dosage of CC was fixed at 3.0 g/day for the 12-week study. After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks, then allocated randomly to three groups for the final 4 weeks: group A, sevelamer 6.0 g/day; group B, sevelamer 3.0 g/day and CC 3.0 g/day; group C, CC 3.0 g/day. The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration (Ca) was 9.0-10.0 mg/dL. Of the 86 patients, 62 finished the study without a change of dosage and their data were analyzed (group A, N=16; group B, N=26; group C, N=20). At week 8 compared with week 4, the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A, and decreased significantly in groups B and C, and in group B compared with groups A and C; groups A and C had similar concentrations at week 8. The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer. At week 8 Ca was not significantly changed in group A, whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study, with a high frequency in group A (13/29; 44.8%). In conclusion, there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC. The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy.     

Effect of individual health education on hyperphosphatemia in the Hakkas residential area

Abstract

The Hakka are a sub-ethnicity with unique diet customs in South China. This study investigated hyperphosphatemia in hemodialysis patients in relation to the current Hakka dietary customs and explored health education patterns for hyperphosphatemia control. Two continuous cross-sectional surveys were conducted among the local patients on dialysis. After the first survey, the patients with hyperphosphatemia were semi-randomized into regular (group 1) and individual (group 2) education groups. Regular health education was conducted for both groups. In group 2, the awareness of health knowledge and dietary customs was investigated using a self-designed questionnaire. Based on the questionnaire, individual dietary guidance was given. The second survey was performed after 3 months. In the first survey, a high-phosphorus diet was found in all 46 patients with 43 (93.5%) diagnosed with hyperphosphatemia. In group 1 and group 2, 15 patients and 25 patients completed the two surveys, respectively. In group 1, no patient changed their dietary habits; however, in group 2, some patients did. The level of serum inorganic phosphorus in group 1 increased significantly. In group 2, the data remained stable; the awareness rate of chronic kidney disease–mineral and bone disorder (CKD–MBD) increased, and six patients with good compliance showed decreased serum inorganic phosphorus (p?=?0.046). High-phosphorus dietary customs and low CKD–MBD knowledge awareness are important reasons for the difficulty in hyperphosphatemia control of patients on dialysis in the Hakka region. Individual health education led by medical staff might be helpful in hyperphosphatemia control, but the pattern still needs further exploration.     

Relationship between dietary protein intake and nutritional status in maintenance hemodialysis patients

Objective To assess the influence of protein intake on nutritional status and mineral metabolism in patients with maintenance hemodialysis (MHD). Methods A cross-sectional study and a prospective cohort study were conducted. According to dietary protein intake (DPI), patients were divided into two groups: DPI≥1.2 g?kg-1?d-1 group (HP group) and DPI＜1.2 g?kg-1?d-1 group (NP group). One hundred and twenty-six MHD patients were enrolled in the cross-sectional study and their datum of dietary intake, as well as laboratory examinations were recorded. In the prospective cohort study lasted 2 years, 32 MHD patients were enrolled, with their dietary and laboratory examinations being collected every 3 months, and somatometric measurements being recorded at the beginning and the end of the study. Results In the cross-sectional study, the average DPI of HP group was (1.36±0.14) g?kg-1?d-1 and the average DPI of NP group was (1.04±0.09) g?kg-1?d-1. Compared with patients in NP group, patients in HP group had higher DPI, daily energy intake (DEI), normalized protein equivalent of nitrogen appearance rate (nPNA) and serum phosphate, and lower carbon dioxide combining power (CO2CP) (all P＜0.05) . There was no difference between two groups in hemoglobin, total protein, albumin, total cholestoral, blood calcium and intact parathyroid hormone (iPTH). In the prospective cohort study, the average DPI of HP group was (1.35±0.13) g?kg-1?d-1 and the average DPI of NP group was (1.05±0.11) g?kg-1?d-1. During the follow-up period, there were no significant differences in times comparison (all Ptime＞0.05). There was higher DPI, nPNA and serum phosphate, and lower CO2CP in HP group, than those in NP group (all Pgroup＜0.05). In terms of hemoglobin, total protein, albumin, total cholestoral and somatometric measurements, there was no difference between two groups (all Pgroup＞0.05). Conclusions DPI around 1.05 g?kg-1?d-1 can satisfy the nutritional requirement in MHD patients with good nutrional status, and ameliorate hyperphosphatemia and acidosis.     

Can Helicobacter pylori Colonization Affect the Phosphate Binder Pill Burden in Dialysis Patients?

Phosphate binder pill (PBP) burden is a significant problem in dialysis patients. Phosphate absorption through the paracellular pathway increases in relatively acidic pH. In this study, we evaluated the effect of factors contributing to duodenal pH—Helicobacter pylori (HP), proton pump inhibitors (PPIs), and NaHCO₃ capsules—on PBP burden. We evaluated 255 dialysis patients with gastric biopsies and excluded patients with low Kt/V, gastrectomy, and parathyroidectomy. Patients were divided into groups and subgroups regarding HP existence, use of PPI, or NaHCO₃ capsules. HP+ group had significantly higher PBP burden and PBP equivalent doses (P < 0.001; both). HP+ subgroup not using daily PPIs or NaHCO₃ capsules had the highest PBP burden and PBP equivalent doses (P < 0.001; both). HP? subgroups had similar PBP and PBP equivalent doses (P = 0.446 and P = 0.382; respectively). HP colonization might affect the PBP burden in dialysis patients due to a decrease of duodenal pH.     

Coronary Artery Calcification in Patients on Chronic Hemodialysis: Evaluation by Electron Beam Computed Tomography

Abstract: In patients on chronic hemodialysis, the incidence of cardiovascular events and mortality rate are higher than those in the general population. These events are associated with coronary, aortic valve, or mitral valve calcification, and show a poor prognosis. However, no study has investigated coronary or cardiac valve calcification in patients on chronic hemodialysis and its prognosis. In this study, we performed electron beam computed tomography (EBCT) in 400 patients who underwent chronic hemodialysis at four dialysis units in Okinawa Prefecture, Japan, between 1996 and 2003, and measured the coronary artery calcification score (CACS), aortic valve calcification score (AVCS), and mitral valve calcification score (MVCS) to analyze the association of these parameters with the prognosis. In addition, we examined the effects of sevelamer hydrochloride, which reduces the serum phosphorus level, reducing CACS. We reached the following conclusions with respect to the following examination items: (i) Factors involved in an increase in CACS in patients undergoing dialysis: in these patients with a rapid increase in CACS, the serum triglyceride and LDL cholesterol levels were higher than the values in the control group; (ii) Cut‐off value of CACS influencing the outcome in patients on dialysis: we reviewed 104 chronic dialysis patients after EBCT was initiated. The group with a CACS of 200 or more showed a significantly poorer outcome compared to the group with a CACS of less than 200; (iii) Accuracy (sensitivity, specificity) of CACS screening on EBCT: we investigated the sensitivity and specificity of CACS based on the presence or absence of coronary artery disease on coronary angiography. The CACS values ranged from 100 to 3000, and their diagnostic accuracy was not satisfactory. Therefore, in patients without symptoms, EBCT may not be appropriate for coronary disease screening; (iv) Does sevelamer hydrochloride inhibit an increase in CACS by reducing the serum phosphorus level in patients on chronic hemodialysis?: in 98 patients on dialysis, this agent reduced the serum phosphorus level, and we examined whether it inhibits an increase in CACS. However, no significant results have been obtained due to a short follow‐up period; and (v) Correlations of CACS, AVCS, and MVCS with the outcome in patients on hemodialysis: AVCS was correlated with the outcome. Aortic valve calcification may markedly influence cardiac hemodynamics.     

Effectiveness of lanthanum carbonate treatment used in combination with calcium carbonate in hemodialysis patients with hyperphosphatemia

Objective To evaluate the effect and safety of the combination of lanthanum carbonate and calcium carbonate in controlling the phosphate level of hemodialysis patients with hyperphosphatemia. Methods Seventy-three patients who developed hyperphosphatemia after hemodialysis were involved, and of which twelve patients complicated with hypercalcemia were put in the group without calcium. The other patients were divided into 3 groups: 21 patients in calcium carbonate group, 32 patients in lanthanum carbonate group and 20 patients in combination group. All the subjects took blood test every month. Results The level of phosphorus decreased in all the subjects participated in the trial (P＜0.01). The level of phosphatemia in combination group decreased dramatically (P＜0.01) and had little effect on calcium and parathyroid hormone. Osteoporosis and valvular calcification were the same as the begin of the trial. Conclusions The combination of lanthanum carbonate and calcium carbonate is more effective than alone. The incidences of adverse effects such as gastrointestinal, hypercalcemia, nausea, vomiting and constipation are low.     

高磷通过局部环氧化酶2途径刺激尿毒症患者甲状旁腺细胞增生

目的 探讨尿毒症时高磷是否通过局部环氧化酶2( COX2)途径刺激人甲状旁腺细胞增生和功能亢进.方法 收集19例行甲状旁腺切除术的尿毒症患者甲状旁腺组织,通过免疫组化和免疫共染法观察COX2和增殖细胞核抗原(PCNA)的表达和分布.进行人甲状旁腺细胞原代培养,分别予高磷和正常磷干预,48 h后检测两组细胞上清液甲状旁腺激素(iPTH)水平;应用Western印迹和实时PCR方法观察细胞中COX2及PCNA的表达.结果 在获取的62枚尿毒症甲状旁腺结节中43枚为结节性增生,19枚为弥漫性增生,均观察到大量PCNA阳性细胞和COX2高表达.在弥漫性和结节性增生的甲状旁腺组织中,分别有80.60％及85.20％的COX2阳性细胞同时表达PCNA.在体外原代培养的尿毒症患者甲状旁腺细胞中,高磷能显著增加iPTH分泌,同时显著上调COX2及PCNA蛋白和基因表达.结论 高磷可能通过局部COX2表达和代谢途径参与尿毒症甲状旁腺细胞增生和功能亢进.     

调整腺嘌呤饮食磷含量制作慢性肾病高磷血症的小鼠模型

目的：通过调整腺嘌呤饮食中的磷水平,建立慢性肾脏病伴高磷血症的小鼠模型。方法：将雄性C57BL/6小鼠分为腺嘌呤饮食组（腺嘌呤0.2%,钙1.0%,磷0.6%）及其对照组（钙1.0%,磷0.6%）、腺嘌呤联合高磷饮食组（腺嘌呤0.2%,钙0.6%,磷1.0%）及其对照组（钙0.8%,磷0.6%）,每组各7只。于造模前、造模4周记录体重,测血尿素氮（BUN）、钙（Ca）、磷（P）水平,4周后取肾脏组织,RT?PCR检测肾纤维化指标包括Ⅰ型胶原蛋白（CollagenⅠ）、纤连蛋白（fibronectin,FN）、纤溶酶原激活物抑制剂?1（plasminogen activator inhibitor?1,PAI?1）以及炎症指标肿瘤坏死因子?α（tumor necrosis factor α,TNF?α）、白细胞介素?1β（interleukin?1β,IL?1β）、细胞间黏附分子?1（intercellular adhesion molecule?1,ICAM?1）等的表达情况。结果：与相应的对照组比,腺嘌呤饮食组4周时体重降低,血BUN明显升高,为（41.15 ± 4.59）mmol/L;Ca、P轻度升高,分别为（2.62 ± 0.16）mmol/L、（2.22 ± 0.26）mmol/L（P < 0.05）。腺嘌呤联合高磷饮食组造模4周时血BUN［（14.68 ± 3.57）mmol/L］轻度升高、P［（2.97 ± 0.29）mmol/L］明显升高（P < 0.05）,血Ca水平无明显差异。RT?PCR显示腺嘌呤饮食组和腺漂呤联合高磷饮食组小鼠肾脏组织中CollagenⅠ、FN、PAI?1、TNF?α、IL?1β、ICAM?1表达水平均较相应对照组升高。结论：腺嘌呤联合高磷饮食饲喂C57BL/6小鼠4周即可建立高磷血症模型,同时伴有轻度肾功能下降、肾脏纤维化,是制备慢性肾脏病伴高磷血症小鼠模型的可行方法。     

爱西特联合碳酸钙治疗血液透析患者高磷血症的疗效观察

目的 观察爱西特联合碳酸钙治疗血液透析患者高磷血症的疗效.方法 将72例存在高磷血症的维持性血液透析患者随机平分为三组,牡蛎碳酸钙组（A组）、爱西特组（B组）和牡蛎碳酸钙＋爱西特组（C组）,每组24例,治疗前、治疗1个月、3个月和6个月检测其血磷、血钙、白蛋白、血红蛋白和血清全段甲状旁腺激素（iPTH）的水平并进行比较分析.结果 与治疗前比较,A组血清磷稍有下降,但差异无统计学意义,A组中有2例（8.3％）血清磷小于1.78 mmol/L;B组血清磷明显下降,治疗3个月降至最低（P＜0.05）,治疗6个月较治疗3个月无明显变化,B组中有4例（16.7％）血清磷小于1.78 mmol/L;C组血清磷下降最明显（P＜0.05）,治疗3个月降至最低,治疗6个月较治疗3个月无明显变化,C组中有8例（33.3％）血清磷小于1.78 mmol/L;与B组治疗3个月相比,C组的血磷明显下降（P＜0.05）;三组血钙、白蛋白、血红蛋白和iPTH的水平无明显变化.结论 爱西特联合碳酸钙能有效治疗血液透析患者的高磷血症,疗效优于单用爱西特和碳酸钙.