Janssen M J, van der Kuy A, ter Wee P M, van Boven W P
Hospital Pharmacy Midden-Brabant, Tilburg, The Netherlands.
Clin Nephrol. 1996 Feb;45(2):111-9.
Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used.
Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups.
In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance.
预防尿毒症患者的继发性甲状旁腺功能亢进需要纠正高磷血症和低钙血症。为避免铝中毒，含钙的磷结合剂越来越多地被使用，以取代氢氧化铝。最近的研究表明，醋酸钙具有理想磷结合剂的许多特性。例如，与碳酸钙相比，它是一种更易溶解的盐。然而，如果在饭前几分钟空腹服用碳酸钙，这一优势可能会消失。我们在一项对53例定期血液透析患者的随机前瞻性研究中，考察了三种不同磷结合剂的疗效。采用钙浓度为1.75 mmol/l的透析液进行碳酸氢盐透析。经过为期三周的洗脱期后，患者分别接受氢氧化铝（对照组）、醋酸钙或碳酸钙作为其磷结合剂。指导患者在饭前几分钟空腹服用钙盐，而在进餐时服用氢氧化铝。每月测定血清钙、磷、完整甲状旁腺激素和碱性磷酸酶水平。通过询问患者使用了哪种磷结合剂以及每日剂量，每月评估患者的依从性。
氢氧化铝往往是最有效的磷结合剂。醋酸钙在12个月时每日所需平均剂量±标准误为5.04±0.60 g，相当于10.1±1.20片500 mg的片剂。然而，需要与氢氧化铝联合用药（每日1.29±0.54 g，相当于2.6±1.08片500 mg的片剂）。碳酸钙每日所需剂量似乎为2.71±0.48 g，相当于5.4±0.95粒500 mg的胶囊，辅助每日氢氧化铝剂量为0.69±0.27 g，相当于1.4±0.55片500 mg的片剂（p = 0.0055）。因此，醋酸钙和碳酸钙治疗组患者的元素钙每日平均剂量相当（1.28±0.15 g对1.09±0.19 g；无显著性差异）。醋酸钙治疗组高钙血症发作（白蛋白校正血清钙水平高于2.80 mmol/l）的发生率为18%，而碳酸钙治疗组为31%（p < 0.005）。氢氧化铝治疗组患者均未发生高钙血症发作。各组间碱性磷酸酶、完整甲状旁腺激素和铝的平均血清浓度无差异。
在慢性间歇性血液透析患者中，每克给予的元素钙与醋酸钙或碳酸钙结合的磷是等效的，前提是在饭前几分钟空腹服用碳酸钙。为使血清磷和完整甲状旁腺激素水平保持在可接受范围内，碳酸钙所需的胶囊数量以及克数总量均显著减少。这可能会提高患者的依从性。
