Safety and Efficacy of Sevelamer in the Treatment of Uncontrolled Hyperphosphataemia of Haemodialysis 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.

Section: Discussionmentioning

confidence: 88%

Efficacy of Combined Sevelamer and Calcium Carbonate Therapy for Hyperphosphatemia in Japanese Hemodialysis Patients

Iwasaki¹,

Takami²,

Tani³

et al. 2005

“…Recently, sevelamer, which is a much‐awaited, non‐calcium, nonaluminum P binder, has become clinically available in Japan. Various clinical trials have shown that sevelamer, as well as the Ca‐containing P binders, had a beneficial effect on P management in dialysis patients (5–10). In Japanese clinical trials on sevelamer treatment, it was demonstrated that the compound could improve bone mineral derangement in ESKD (11).…”

Section: Phosphate Binders In Japanmentioning

confidence: 99%

“…Recently, a novel, non‐calcium phosphorus (P) binder, sevelamer hydrochloride (sevelamer), has become available in Japan. Sevelamer has been reported to be effective in P management and on reduced Ca load in dialysis patients in European countries and the United States (5–11). Sevelamer might bring about an alternative therapeutic strategy for bone and mineral disarrangement of CKD, which is reflected in the Kidney Disease Outcomes Quality Initiatives (K/DOQI) Clinical Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease (12).…”

mentioning

confidence: 99%

Combination Therapy with Sevelamer Hydrochloride and Calcium Carbonate in Japanese Patients with Long‐Term Hemodialysis: Alternative Approach for Optimal Mineral Management

Ogata¹,

Koiwa²,

Shishido³

et al. 2005

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.

“…Almost all dropouts were due to gastrointestinal problems, such as the onset or exacerbation of constipation, abdominal bloating, nausea or abdominal pain. In this regard, Almirall et al (15) reported that 67% of patients treated with sevelamer developed gastrointestinal symptoms. It is possible that the high number of dropouts in our study was due to the use of 3.0 g/day of Pi binders in both groups, and/or failure to reduce the dose of these drugs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Sevelamer Hydrochloride With Colestimide, Administered Alone or in Combination With Calcium Carbonate, in Patients on Hemodialysis

Itoh

Tanaka

Hashiguchi³

et al. 2008

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.