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.