bixalomer and Kidney-Failure--Chronic

Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer is a nonabsorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study compared the efficacy and safety of bixalomer versus sevelamer hydrochloride for controlling hyperphosphatemia in hemodialysis patients. This was a multicenter, randomized open-label, non-inferiority study. The primary endpoint was serum phosphate on completion of treatment. Administration of bixalomer was started at 1.5 g/day and adjusted to a maximum of 7.5 g/day depending on the serum phosphate level. Sevelamer hydrochloride was started at 3.0 or 6.0 g/day and adjusted to a maximum of 9.0 g/day. Treatment was continued for 12 weeks. Fifty-five patients were randomized to each treatment group. After 12 weeks, the baseline adjusted mean serum phosphate level was 5.87 mg/dL in the bixalomer group and 5.55 mg/dL in the sevelamer group, with a difference of 0.31 mg/dL and 95% confidence interval (CI) of [-0.13 to 0.76]. The upper limit of the 95%CI for the difference of the mean serum phosphate level between the two groups was <1.0 mg/dL, which was the non-inferiority margin in this study. Thus, non-inferiority of bixalomer to sevelamer was confirmed. The incidence of adverse events was lower in the bixalomer group, and bixalomer did not promote acidosis. Bixalomer achieved a similar reduction of serum phosphate to sevelamer, while causing fewer adverse reactions. Consequently, the usefulness of bixalomer for treating hyperphosphatemia was confirmed.

Topics: Adult; Aged; Chelating Agents; Female; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Male; Middle Aged; Phosphates; Polyamines; Renal Dialysis; Sevelamer; Treatment Outcome

The serum bicarbonate (HCO3(-)) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end-stage renal disease on HD, who orally ingested a dose of SH (≥2250 mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO3(-) levels were under 18 mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO3(-) level under 18 mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2 ± 1.1 g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO3(-) levels increased from 16.3 ± 1.4 to 19.6 ± 1.7 mmol/L (P < 0.05). Metabolic acidosis was not observed in four patients (serum HCO3(-) level: 20.3 ± 0.7 mmol/L) likely because they were taking 3 g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer.

Topics: Acidosis; Calcium Carbonate; Chelating Agents; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polyamines; Renal Dialysis; Sevelamer

In Japan, the clinical use of bixalomer, a new polymer preparation like sevelamer hydrochloride, became possible from 2012. In our study, in order to investigate the clinical characteristics of this new phosphorus (P) binder, bixalomer in a clinical practice, for 18 cases of hemodialysis patients at our hospital being treated with sevelamer hydrochloride, we switched the P binder to bixalomer, and compared the laboratory parameters before and after switching. Subjects used for analysis were nine cases in which it was possible to use bixalomer continuously for 10 months. The laboratory parameters measured were the concentrations of serum P, corrected calcium (Ca), whole parathyroid hormone (PTH), albumin and alkaline phosphatase (ALP) as indicators of mineral and bone disorder, and serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) as indicators of lipid metabolism. Regarding the results after switching to bixalomer and starting treatment using the same dosage as the dosage previously used for sevelamer hydrochloride, there were many cases that showed increasing P concentrations that required increasing the dosage of bixalomer, the dosage after switching was increased significantly (P=0.002). In the comparison of laboratory parameters before and after switching, the concentrations of serum P and albumin decreased significantly (P=0.035 and 0.033). From these results, it was considered that the decreases in serum P concentrations were due not only to the effects of bixalomer, but that suppression of food intake by patients was another reason. There were no significant changes in corrected Ca, whole PTH or ALP. In addition, after changing the P binder, serum HDL-C concentration decreased significantly (P=0.015) and LDL-C increased significantly (P<0.001), and serum TG concentration showed no significant changes. This indicated that the beneficial effects of bixalomer on lipid metabolism may be less than those of sevelamer hydrochloride.

Topics: Aged; Alkaline Phosphatase; Biomarkers; Calcium; Chelating Agents; Female; Humans; Hyperphosphatemia; Japan; Kidney Failure, Chronic; Lipid Metabolism; Lipids; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Polyamines; Renal Dialysis; Sevelamer

It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P=0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.

Topics: Abdominal Pain; Aged; Calcium; Chelating Agents; Constipation; Diarrhea; Dyspepsia; Female; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Hyperphosphatemia; Japan; Kidney Failure, Chronic; Male; Parathyroid Hormone; Phosphorus; Polyamines; Renal Dialysis; Sevelamer; Surveys and Questionnaires

In 2012, bixalomer was launched as new non-calcium (Ca) containing phosphorus (P) binder, increasing the choices available for the treatment of hyperphosphatemia. In this study, among the maintenance dialysis patients at our hospital, we newly administered bixalomer to 21 patients who were not receiving any P binders, and switched to bixalomer for 13 patients who had been receiving sevelamer hydrochloride and 23 patients who had been receiving lanthanum carbonate. The initial dosage of bixalomer was set as 1500 mg/day for new administration patients and dosage equivalent to that of the previously-used P binder for patients who were switched to bixalomer. The dosage of bixalomer was increased if the effects were insufficient. The serum P, Ca and intact parathyroid hormone concentrations as well as serum pH, HCO3 concentration and base excess were evaluated prior to administering bixalomer, 3 months and 6 months after administering bixalomer. For the group who were newly administered bixalomer, significant reductions in serum P concentrations were seen (P<0.01) and no significant changes were seen in clinical test items that serve as indices for acidosis. For the group who were switched from sevelamer hydrochloride to bixalomer, significant reductions in serum P concentrations were seen (P<0.01) together with significant improvements in acidosis (P<0.01). For the group who were switched from lanthanum carbonate to bixalomer, by increasing the dosage of bixalomer to approximately three times the dosage of lanthanum carbonate, it was possible to maintain post-switch serum P concentrations at almost the same levels as before the switch. Furthermore, there were minor, yet significant improvements in acidosis (P<0.01). From these results, it was shown that bixalomer can be useful treatment alternative in dialysis patients for whom it is necessary to change the P binder due to insufficient management of serum P concentrations or development of acidosis.

Topics: Aged; Calcium; Chelating Agents; Female; Follow-Up Studies; Humans; Hydrogen-Ion Concentration; Hyperphosphatemia; Japan; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Polyamines; Prospective Studies; Renal Dialysis; Sevelamer

Bixalomer (Bix) is an amine-functional polymer, non-calcium-containing phosphate (P) binder, and has been clinically available in Japan recently. Bix is expected to cause fewer gastrointestinal (GI) side-effects as compared with sevelamer hydrochloride (SH), because of less expansion of Bix in the GI tract. In this prospective observational study, we evaluated changes in GI symptoms by the Gastrointestinal Symptom Rating Scale (GSRS) score in long-term hemodialysis (HD) outpatients with SH-associated GI symptoms who switched to Bix from SH. A total of 114 patients (age 63.7±10.8 year (mean±SD), female 65.5%, HD vintage 11.2±8.6 years, diabetes mellitus 27.4%) were enrolled. The GSRS score was checked at 0 and 12 weeks after the start of Bix. Bix was started at the initial dose of 750 mg/day, and then was titrated. Serum albumin, P and corrected calcium levels did not significantly change during Bix treatment. However, serum low-density lipoprotein-cholesterol and bicarbonate levels significantly increased during Bix treatment (P<0.001). In GSRS scores, total and domain-specific scores, including constipation, diarrhea, reflux and abdominal pain were significantly reduced at 0, 4, 12 and 24 weeks as compared with those at 0 weeks (P<0.05). This study shows that Bix was well tolerated and managed hyperphosphatemia effectively after switching from SH in Japanese patients on long-term HD. In addition, Bix might be less often associated with GI symptoms as compared with SH.

Topics: Abdominal Pain; Bicarbonates; Calcium; Chelating Agents; Cohort Studies; Constipation; Female; Follow-Up Studies; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Hyperphosphatemia; Japan; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Phosphates; Phosphorus; Polyamines; Prospective Studies; Renal Dialysis

Bixalomer is a nonabsorbable polymer that binds phosphate in the gastrointestinal tract and lowers the serum phosphate level by inhibiting phosphate absorption. The safety and efficacy of long-term bixalomer treatment were assessed in Japanese hemodialysis patients with hyperphosphatemia. This was a multicenter open-label study with a 48-week treatment period. The main efficacy endpoints were the serum phosphate level and rate of achieving the target serum phosphate range (3.5-6.0 mg/dL). Bixalomer was initiated at a dose of 1.5 g/day, which was increased to a maximum of 7.5 g/day depending on the serum phosphate response. Of 248 subjects who started treatment, 179 completed the study. The mean serum phosphate level decreased over time and remained around 5.5 mg/dL from weeks 16 to 48. The target serum phosphate level was reached in >50% of subjects by week 7 and was maintained in 65.2% to 75.9% until week 48. The incidence of adverse events and adverse drug reactions was 94.4% and 29.4%, respectively. There was a potential relationship with the study drug for four serious adverse events (ischemic colitis, hemorrhagic intestinal diverticulum, esophageal ulcer, and acute cholecystitis), which occurred in one patient each. Constipation was the most common adverse drug reaction (21.0%). Most adverse events and adverse drug reactions occurred soon after starting administration, and their incidence did not increase during long-term treatment. Bixalomer did not reduce the bicarbonate level or promote metabolic acidosis. Bixalomer is clinically useful for the long-term treatment of hyperphosphatemia.

Topics: Aged; Asian People; Female; Gastrointestinal Agents; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Male; Middle Aged; Phosphates; Phosphorus; Polyamines; Renal Dialysis; Treatment Outcome