Comparison of sevelamer hydrochloride with colestimide, administered alone or in combination with calcium carbonate, in patients on hemodialysis

Since hyperphosphatemia in hemodialysis patients can cause secondary hyperparathyroidism and promotes vascular calcification, serum phosphate (Pi) levels must be controlled by phosphate binders. Although sevelamer and colestimide are known as similar non-calcium, non-aluminum phosphate binders in hemodialysis patients, there are no studies that compare the effects of the two agents as either a monotherapy or in combination with calcium carbonate (CaCO3). We randomly allocated 62 hemodialysis patients with hyperphosphatemia to treatment with sevelamer (3.0 g/day) and colestimide (3.0 g/day). During the study, 35 subjects dropped out, leaving 13 in the sevelamer group and 14 in the colestimide group. After a 2-week CaCO3 washout, all subjects received the monotherapy for 4 weeks and then CaCO3 (3.0 g/day) was added for another 4 weeks. Serum corrected calcium levels tended to decrease in both groups during the washout period and monotherapy, but there was no significant difference between the two groups after the addition of CaCO3. Although the calcium x phosphorus product (Ca x P) in the two groups increased during the washout period, there was no significant change or difference between the two groups during monotherapy. However, the addition of CaCO3 significantly reduced serum Pi at Week 8 compared to that at Week 0 in both groups, and significantly lowered Ca x P only in the sevelamer group, but not in the colestimide group(.) In this short-term study, sevelamer and colestimide similarly ameliorated hyperphosphatemia, but the combination of sevelamer and CaCO3 was more effective than colestimide with CaCO3 in controlling the Ca x P product, and it may improve cardiovascular mortality in hemodialysis patients.     

Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management

Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.     

Impact of sevelamer hydrochloride and the K/DOQI guidelines

Sevelamer hydrochloride (SH) was registered as a new drug under the Japanese national health insurance scheme in 2003, and the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for the treatment of renal osteodystrophy were released the same year. At that time, treatment objectives for hemodialysis outpatients at the Kojinkai Ishimaki Clinic were settled established and the outcomes reviewed 18 months later. The relationship between the type and dosage of phosphate binder (PB), and the concentrations of adjusted calcium (Ca), phosphorus (P), intact parathyroid hormone (PTH), and bone alkaline phosphatase (BAP) was examined. Patients receiving calcitriol or maxacalcitol intravenous pulse therapy, or who had undergone simultaneous pancreas-kidney transplant, were excluded from this analysis. The PB was CaCO3 in 60% of cases, SH in 33.3%, and a combination of both in 21.9%; no PB was used in 6.7% of cases. The dosage of CaCO3 was 2.8+/-1.0 g/day, and 1alpha-hydroxy activated vitamin D3 (VD) was 0.46+/-0.24 microg/day; the respective concentrations of adjusted Ca, P, intact PTH, and BAP were 9.4+/-0.7 mg/dL, 5.6+/-1.7 mg/dL, 104+/-83.9 pg/mL, and 22.7+/-10.9 IU/L. In the SH monotherapy group, the dosage of SH was 3.9+/-0.725 g/day, and VD 0.62+/-0.21 microg/day, and the concentrations for adjusted Ca, P, intact PTH, and BAP were 9.6+/-0.4 mg/dL, 6.2+/-1.5 mg/dL, 150+/-42.9 pg/mL, and 38.5+/-14.2 IU/L, respectively. In the combined therapy group, the dosage of CaCO3 was 2.9+/-0.9 g/day, SH was 3.3+/-1.1 g/day, VD was 0.53+/-0.27 microg/day, and the respective concentrations were 9.2+/-1.0 mg/dL, 5.7+/-1.4 mg/dL, 160+/-107.8 pg/mL, and 31.3+/-42.0 IU/L. One-third of all subjects were administered SH, either as monotherapy or in combination with CaCO3, and in these patients the dosage of VD was able to increase.     

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.     

Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese hemodialysis patients

In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium x phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium x phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5-5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium x phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.     

Clinical features and hyperplastic patterns of parathyroid glands in hemodialysis patients with advanced secondary hyperparathyroidism refractory to maxacalcitol treatment and required parathyroidectomy

We have previously suggested that when parathyroid glands progress to nodular hyperplasia, secondary hyperparathyroidism (2HPT) may be refractory to medical treatments, including treatment with Maxacalcitol (OCT). In the present study we evaluated the clinical features and hyperplastic patterns of parathyroid glands in patients who underwent parathyroidectomy (PTx) after being withdrawn from OCT. One hundred and eighty-seven advanced 2HPT patients who had been withdrawn from OCT and required PTx were enrolled. At the start of OCT treatment, the patients had a mean age of 55.3 years and had been receiving hemodialysis (HD) for a mean period of 149 months. At the start of OCT treatment and at PTx, the mean intact PTH (i-PTH) levels were 772.8 +/- 446.0 and 855.5 +/- 420.5 pg/mL, respectively. The main reasons for withdrawal of OCT treatment were persistently high PTH (n = 148), hypercalcemia (n = 79), hyperphosphatemia (n = 65), and progressive symptoms (n = 60). We classified the parathyroid glands by hyperplastic pattern into four categories: diffuse hyperplastic gland (D), early nodularity in diffuse hyperplastic gland (EN), nodular hyperplastic gland (N), and single nodular gland (SN). The mean total excised gland weight was 2592.6 mg. Out of a total of 706 glands, 118 were classified as D, 66 as EN, 436 as N, and 86 as SN. All patients had at least one nodular hyperplastic gland or single nodular gland. The mean number of nodular hyperplastic glands and/or single nodular glands was 2.9. All hemodialysis patients with advanced OCT-refractory 2HPT who underwent PTx had at least one nodular hyperplastic gland or single nodular gland.     

Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients

Sevelamer hydrochloride (SH) has been reported to aggravate metabolic acidosis and hyperkalemia. This study was performed to evaluate acid-base status and serum potassium changes after replacing SH with lanthanum carbonate (LC) in hemodialysis patients. SH was prescribed for 24 weeks in 14 stable hemodialysis patients and replaced by LC in a similar treatment schedule. Laboratory tests, including indices of acid-base status, nutrition, bone/mineral metabolism, and dialysis adequacy, were performed monthly during the study. Dialysate bicarbonate, potassium and calcium concentrations remained constant. Serum bicarbonate and pH rose, and serum potassium dropped significantly under LC. Alkaline phosphatase also decreased significantly under LC. No significant differences were observed in the other studied parameters between the two treatment periods. Control of serum phosphate was similar under both phosphate-binders and no differences were observed in calcium, Ca × P product, CRP, or lipid levels. Dialysis adequacy was constantly kept within K/DOQI target-range. Although full compliance to treatment was reported, three patients on LC complained of gastrointestinal upset and/or a metallic taste, and four had difficulty chewing the LC tablet. LC improves metabolic acidosis and hyperkalemia in hemodialysis patients previously under SH. Although both medications are well-tolerated, the gastrointestinal side-effects appear to occur more frequently with LC; a fact that, together with difficulties in chewing the tablet, may result in decreased compliance.     

Cinacalcet hydrochloride therapy for secondary hyperparathyroidism in hemodialysis patients

This study compared the efficacy of a cinacalcet‐based regimen with unrestricted conventional therapy (vitamin D and phosphate binders) for achieving Kidney Disease Outcome Quality Initiative (K/DOQI) targets for dialysis patients. In this multicenter, prospective study, hemodialysis patients with poorly controlled secondary hyperparathyroidism (SHPT) were randomized to receive a cinacalcet‐based regimen (n = 55) or a conventional therapy (n = 27). Doses of cinacalcet, vitamin D sterols, and phosphate binders were adjusted during a 12‐week dose‐titration phase to achieve intact parathyroid hormone (iPTH) levels ≤ 31.8 pmol/L. The primary end point was the percentage of patients with values in this range during a 24‐week efficacy‐assessment phase. The clinical response to 36‐week cinacalcet treatment was evaluated. A dual energy X‐ray absorptiometry was performed before and after 36 weeks of cinacalcet therapy. Fifty‐eight percent of the cinacalcet group reached the primary end point, as compared with 19% of the conventional therapy group (P = 0.001). A higher percentage of patients receiving the cinacalcet‐based regimen versus conventional therapy achieved the targets for calcium, phosphorus and Ca × P. Achievement of targets was greatest in patients with less severe disease (intact PTH range, 31.8 to 53 pmol/L). Cinacalcet therapy increased proximal femur bone mineral density (BMD), but did not affect the lumbar spine. Itching intensity decreased significantly. Cinacalcet based treatment facilitates achievement of the K/DOQI targets for iPTH and bone mineral metabolism compared with conventional therapy in hemodialysis patients. Suppression of iPTH with cinacalcet reverses bone loss in the proximal femur. Cinacalcet alleviated itching.     

Different routes bridging calcium in Japanese hemodialysis patients

There is growing evidence that not only serum calcium concentration but also excess calcium load is associated with vascular calcification and mortality in hemodialysis patients. Calcium load in hemodialysis patients cumulatively comes from three different routes: oral intake of calcium including calcium-based phosphate binders, traffic of calcium from/to dialysate, and calcemic action of vitamin D. The K/DOQI guidelines recommend sevelamer hydrochloride instead of calcium-containing phosphate binders to control serum phosphate concentration. However, in Japan, both kinds of phosphate binders are used concomitantly, mainly because Japanese patients are prone to a higher incidence of sevelamer-associated adverse events such as gastrointestinal symptoms. Regarding the calcium concentration of dialysate (D-Ca) in Japan, 3.0 mEq/L is more popular than 2.5 mEq/L. Calcium loaded through 3.0 mEq/L dialysate may lead to metastatic calcification rather than to bone formation because serum phosphate concentration rebounds several hours after the end of each hemodialysis session when plasma pH is still high. In contrast, use of 2.5 mEq/L dialysate may result in an unfavorable increase of intact parathyroid hormone particularly when the amount of oral calcium intake is reduced. Although a higher dose of vitamin D is required to counteract the stimulation of parathyroid glands, hypercalcemia is less likely with 2.5 mEq/L dialysate. As the new K/DOQI guidelines are released, it is time to discuss the appropriate D-Ca as well as doses and kinds of phosphate binders and vitamin D for the comprehensive management of Japanese hemodialysis patients.     

Dose determination of cinacalcet hydrochloride in Japanese hemodialysis patients with secondary hyperparathyroidism

Cinacalcet hydrochloride is a calcimimetic agent that activates the calcium-sensing receptor on the surface of parathyroid cells and inhibits parathyroid hormone (PTH) secretion. To manage secondary hyperparathyroidism, cinacalcet, which lowers PTH levels without increasing serum calcium, phosphorus and calcium-phosphorus product (Ca x P) levels, may provide a new potential therapy. To identify the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism, this double-blind, placebo-controlled, parallel, dose-finding study was conducted. One hundred and twenty Japanese hemodialysis patients with intact PTH levels greater than or equal to 300 pg/mL were randomized into four groups: placebo, and 12.5, 25 and 50 mg of cinacalcet. The treatment period was three weeks followed by a two-week follow-up observation period. Cinacalcet decreased serum intact PTH levels in a dose-dependent manner, and also decreased serum calcium, phosphorus, Ca x P, tartrate-resistant acid phosphatase and osteocalcin levels. The treatment with cinacalcet was generally well tolerated in this study. However, the incidence of treatment-related adverse events, such as gastrointestinal disorders and hypocalcemia, and the rate of withdrawal from the study due to treatment-related adverse events were higher in the 50 mg dose group than in the other groups. On the basis of both efficacy and safety results, 25 mg has been identified as the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism.     

Dose-response study of 22-oxacalcitriol in patients with secondary hyperparathyroidism

The dose-response relationships and the safety of administering 22-oxacalcitriol (OCT) to patients with secondary hyperparathyroidism (2HPT) under regular three-times-weekly hemodialysis (HD) were evaluated by double-blind parallel group design. A total of 203 patients with 2HPT were randomly allocated into four groups, and 5 microg (Group L), 10 microg (Group M), or 15 microg (Group H) OCT, or placebo (Group P) was administrated at the end of every HD for 12 weeks. Reductions of intact-parathyroid hormone (iPTH) concentration greater than 30% from baseline were observed in 7.7% of Group P as compared to 77.3% of the pooled OCT groups after 12 weeks of treatment (Mantel test: P < 0.001). Time-trends (slopes) of log-iPTH concentration calculated by least-squares line fitting to each patient's data during treatment differed between Group P and the pooled OCT groups (t-test: P < 0.001) and these iPTH slopes decreased dose-dependently (linear trend by t-test: P < 0.001). Slopes of serum calcium corrected for albumin (corrected-sCa) concentrations also differed between Group P and the pooled OCT groups (t-test: P < 0.001), and increased dose-dependently (linear trend by t-test: P < 0.0001). Serum phosphorus and Ca x P product increased significantly only in high dose groups. Slopes of log(iPTH) and corrected-sCa concentrations were reciprocally related. Most adverse events were hypercalcemia and dose-related, but occasionally comprised pruritus or increased serum creatinine phosphokinase. These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT. The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL, and 10 microg when greater than 500 pg/mL for safe and effective treatment. As in the case of PTH, calcium and phosphorus showed dose-dependent increases. It is therefore essential to take precautions as to possible increases in calcium and phosphorus.     

Effects of 22-oxacalcitriol and calcitriol on PTH secretion and bone mineral metabolism in a crossover trial in hemodialysis patients with secondary hyperparathyroidism

The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22-oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run-in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22-Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22-oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism in SHPT.     

血液透析血液灌流对继发甲状旁腺功能亢进的影响

目的观察血液灌流比较血液透析滤过对慢性肾衰竭维持血液透析患者继发性甲状旁腺功能亢进的影响。方法选取2004年8月至2005年11月河北大学第二医院维持性血液透析患者40例，分为2组，比较单次血液透析串联血液灌流（HD＋HP）治疗，及单次血液透析滤过（HDF）治疗前后，患者血甲状旁腺激素（PTH）和磷（P）的清除力和清除百分比。结果单次血液透析串联血液灌流后，慢性肾衰竭维持血液透析患者血PTH下降明显，血钙（Ca）增高。结论血液透析串联血液灌流后患者骨病的临床症状好转；血液灌流可以明显降低患者的PTH，能很好地改善维持性血液透析患者的继发性甲状旁腺功能亢进症状。     

血液透析血液灌流对继发甲状旁腺功能亢进的影响

目的观察血液灌流比较血液透析滤过对慢性肾衰竭维持血液透析患者继发性甲状旁腺功能亢进的影响。方法选取2004年8月至2005年11月河北大学第二医院维持性血液透析患者40例,分为2组,比较单次血液透析串联血液灌流(HD HP)治疗,及单次血液透析滤过(HDF)治疗前后,患者血甲状旁腺激素(PTH)和磷(P)的清除力和清除百分比。结果单次血液透析串联血液灌流后,慢性肾衰竭维持血液透析患者血PTH下降明显,血钙(Ca)增高。结论血液透析串联血液灌流后患者骨病的临床症状好转;血液灌流可以明显降低患者的PTH,能很好地改善维持性血液透析患者的继发性甲状旁腺功能亢进症状。     

继发性甲状旁腺功能亢进患者甲状旁腺切除术后短期钙磷变化的观察与分析

目的 探讨继发性甲状旁腺功能亢进(SHPT)患者行甲状旁腺切除术(PTX)后短期钙磷变化情况并分析其相关因素。方法 回顾性分析于我院行PTX的难治性SHPT患者18例，收集所有患者术前的基线资料和术后第1天、第3天及第7天的血全段甲状旁腺激素(iPTH)、血碱性磷酸酶（ALP）、血钙、血磷等生化指标并进行比较，统计所有患者术后1周的补钙量。采用Pearson和Spearman相关分析研究患者术前血iPTH、血钙、血磷、血ALP水平及术后1周补钙总量的相关性。结果 术后第1天、第3天和第7天患者血iPTH和血磷与术前比较均明显下降(P均＜0.05)；术后第1天血ALP与术前比较明显下降(P＜0.05)；术后第7天血钙与术前比较明显下降（P＜0.05）。术前血iPTH水平与术前血ALP水平呈正相关(r=0.773,P＜0.001)，术后1周补钙量与术前血iPTH水平(r=0.855,P＜0.001)、术前血ALP水平(r=0.925,P＜0.001)均呈正相关。结论PTX治疗难治性SHPT安全有效，能在短期内快速纠正血钙、血磷的代谢紊乱。     

Efficacy of combined sevelamer and calcium carbonate therapy for hyperphosphatemia in Japanese hemodialysis patients

In Japan, calcimimetics and other phosphate binders such as lantanum carbonate are not available for patients on long-term hemodialysis (HD), so we prospectively evaluated the clinical efficacy of the combination of sevelamer hydrochloride and calcium carbonate (CaCO3) for hyperphosphatemia. The study group comprised 65 HD patients who had been administered CaCO3 (>or=1500 mg/day) for hyperphosphatemia [>or=6.0 mg/dL (>or=1.94 mmol/L)]. At the beginning of the study the dose of CaCO3 was reduced by 1500 mg/day and the patients divided into two groups according to the dose of additional sevelamer hydrochloride: group A 2250 mg/day; group B 3000 mg/day. Oral active vitamin D therapy was unchanged. Fourteen patients (21.5%) dropped out because of adverse effects and of the 51 remaining patients 35 (53.8%) suffered from gastrointestinal problems. Serum phosphate concentration decreased significantly [from 7.5+/-0.8 mg/dL (2.42+/-0.26 mmol/L) to 6.6+/-1.3 mg/dL (2.13+/-0.42 mmol/L), P<0.01] in group B only after the 8 weeks of combination therapy. The calcium-phosphate product (CaxPi) also decreased in group B only [from 74.4+/-13.4 mg2/dL2 (5.99+/-1.07 mmol2/l2) to 63.7+/-15.8 mg2/dL2 (5.13+/-1.27 mmol2/l2), P<0.001]. The combination of sevelamer hydrochloride and CaCO3 is a suitable regimen for hyperphosphatemia treatment in HD patients because it avoids both the hypercalcemia of CaCO3 and the adverse effects of sevelamer hydrochloride when each is used as single-drug therapy. The ability of sevelamer hydrochloride to decrease the serum phosphate concentration is 2/3 (2250/1500 mg) that of CaCO3.     

Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients

Fibroblast growth factor 23 (FGF23) is a member of the fibroblast growth factor superfamily which displays a strong phosphaturic action and an inhibition of vitamin D 1-alpha hydroxylase activity. Fourty-six patients undergoing maintenance hemodialysis therapy participated in the study. They were randomly divided into 2 groups, and treated with either 3 g sevelamer hydrochloride+3 g of calcium bicarbonate (CaCO3), or 3 g of CaCO3 alone. Serum FGF23 levels were determined by a sandwich enzyme-linked immunosorbent assay (ELISA) system that detects the intact form of FGF23 molecules. Although the serum inorganic phosphate (Pi) levels were comparable before treatment, the levels were significantly lower in the patients treated with sevelamer hydrochloride+CaCO3 than those with CaCO3 alone after 4 weeks of treatment (P<0.05). Serum FGF23 levels significantly decreased after 4 weeks of the treatment with sevelamer hydrochloride+CaCO3 from the pretreatment levels (P<0.05), while no changes were found in the patients treated with CaCO3 alone. Thus, the use of sevelamer hydrochloride and CaCO3 reduced serum FGF23 levels in dialysis patients presumably through inhibiting phosphate load into the intestine.     

Association of nodular hyperplasia with resistance to cinacalcet therapy for secondary hyperparathyroidism in hemodialysis patients

There have been few long-term prospective studies investigating the effect of cinacalcet on secondary hyperparathyroidism with or without nodular hyperplasia. We examined whether the effect of cinacalcet on secondary hyperparathyroidism differed between patients with or without nodular hyperplasia. Stable hemodialysis patients with secondary hyperparathyroidism resistant to conventional treatment received cinacalcet for 12 months. Based on ultrasonography findings, patients were divided into group S (gland < 500 mm(3) without nodular hyperplasia) and group L (gland ≥ 500 mm(3) with nodular hyperplasia). Serum levels of intact parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, and cross-linked N-terminal telopeptide of type 1 collagen were measured. Thirty-one patients completed the study. The changes of parameters from the baseline did not differ significantly between the two groups after 6 months. However, the percentage reduction of each parameter was significantly smaller in group L compared with group S after 12 months. Nodular hyperplasia is associated with resistance to cinacalcet therapy in patients on chronic dialysis with secondary hyperparathyroidism.     

透析液钙离子浓度对维持性血液透析患者血全段甲状旁腺激素的影响

目的评价不同钙离子浓度的透析液对维持性血液透析(MHD)患者血全段甲状旁腺激素(iPTH)的影响,分析血钙、磷和钙磷乘积与iPTH之间的相关性。方法对2006年1月至3月,上海交通大学医学院附属新华医院肾内科门诊35例长期使用钙离子浓度为1·75mmol/L的透析液进行维持性血液透析的患者,于透析前留取血标本进行血Ca2 、P3-、iPTH测定,并计算钙磷乘积后,改为钙离子浓度为1·25mmol/L或1·50mmol/L的透析液进行维持性血液透析,3个月后于透析前再次留取血标本进行血Ca2 、P3-、iPTH测定,并计算钙磷乘积。结果与使用钙离子浓度为1·75mmol/L透析液比较,使用钙离子浓度为1·25mmol/L或1·50mmol/L透析液3个月后,MHD患者血Ca2 、P3-、钙磷乘积差异无显著性意义,P>0·05,血iPTH明显升高,P<0·01。血iPTH与Ca2 呈显著性负相关,r=-0·45,P<0·01;与P3-及钙磷乘积无相关性,r分别为0·13和-0·03,均P>0·05。结论1·25mmol/L或1·50mmol/L的低钙透析液可以升高MHD患者血清iPTH水平。     

Vitamin D receptor activator reduces oxidative stress in hemodialysis patients with secondary hyperparathyroidism

Treatment with a vitamin D receptor activator (VDRA) has survival benefits probably related to its effects beyond the traditional role in mineral metabolism. We hypothesized that VDRA reduces oxidative stress in hemodialysis (HD) patients. To test this hypothesis, we investigated the effect of VDRA on the oxidative status of albumin in HD patients with secondary hyperparathyroidism. Eleven HD patients with secondary hyperparathyroidism were treated with calcitriol at an intravenous dose of 1.5 μg/week for four weeks. Serum intact parathyroid hormone, calcium and phosphorus were monitored and we measured the amount of oxidized albumin and albumin hydroperoxides form before and after calcitriol treatment. The ratio of oxidized to un-oxidized albumin was determined as a representative marker of oxidative stress. The radical scavenging activity of albumin was also evaluated. After four weeks of calcitriol therapy, there were no significant changes in serum intact parathyroid hormone, calcium, or phosphorus levels; however, the ratio of oxidized to un-oxidized albumin was markedly decreased and serum thiol content was significantly increased after calcitriol treatment. Furthermore, the radical scavenging activity of albumin was greater after calcitriol treatment compared with that of untreated albumin. Our data suggest that intravenous calcitriol treatment reduces oxidative stress and strengthens antioxidant defenses by inhibiting albumin oxidation in HD patients with secondary hyperparathyroidism.