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.

[Clinical investigation of the effect of blood sampling day on serum phosphorus concentration].

Whether the presence or absence of notification about the blood sampling date affects the serum phosphate concentration was examined. After periodical sampling at the beginning of the week with 2-day interval for regular dialysis, the blood was sampled on the midweek day with 1-day interval for dialysis upon the patient's consent right before sampling without an advance notification. In the next month subsequently periodical sampling at the beginning of the week and the sampling on the midweek day were performed after notification of the twice blood sampling before 1 week in advance. Then both serum phosphorus data were comparably investigated. In case the sampling was not notified, there is no difference in the serum concentration between the beginning of the week and the midweek day. On the other hand, in case the sampling was notified, the serum concentration significantly decreased on the weekday compared to that at the beginning of the week. It therefore was risky that the serum phosphorus concentration at the beginning of the week with 2-day interval for dialysis was presumed to be higher value than that on the midweek day with 1-day interval for dialysis. We need to consider the possibility that the presence or absence of notification about the blood sampling date affects the level of serum phosphorus concentration.

Colestimide can be used as a phosphate binder to treat uraemia in end-stage renal disease patients.

Colestimide is a potent therapeutic compound used widely for treatment of hypercholesterolaemia, and it was discovered coincidentally that it can be used to lower the serum phosphate concentration in cases of secondary hyperparathyroidism with refractory hyperphosphataemia. Colestimide is useful for treating hyperphosphataemia in end-stage renal disease (ESRD) patients undergoing haemodialysis. Twenty-eight patients who were being treated for hyperphosphataemia with 3.5+/-1.1 g/day calcium carbonate were enrolled in the study. Colestimide was added to their prescription for 4 weeks at a mean dosage of 2.3 g/day. The serum phosphate concentration decreased significantly from 6.1+/-1.1 mg/dl before treatment to 5.3+/-1.1 mg/dl at 4 weeks (P<0.0001). The calcium-phosphate product also decreased significantly from 59.6+/-11.3 mg/dl(2) before treatment to 50.5+/-12.0 mg/dl(2) (P<0.0001). The serum total cholesterol significantly (P<0.001) decreased at 1 week and remained constant until the end of treatment. Colestimide is a cationic polymer with chloride as the counterion. Its chemical structure resembles that of sevelamer hydrochloride, which is already being used clinically as a phosphate binder. This suggests that colestimide uses the same mechanism as sevelamer hydrochloride to treat hyperphosphataemia. The present results demonstrate that colestimide can function as a Ca-free, aluminium-free, non-absorbable, phosphate binder in ESRD patients. In addition, colestimide can reduce the serum phosphate concentration in combination with calcium carbonate.