Delmez J A, Slatopolsky E
Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110.
Am J Kidney Dis. 1992 Apr;19(4):303-17. doi: 10.1016/s0272-6386(12)80446-x.
Control of phosphorus accumulation in chronic renal insufficiency is crucial to the prevention of secondary hyperparathyroidism and metastatic calcification. In early renal failure, calcitriol levels are normal and parathyroid hormone levels are elevated. The phosphorus levels are maintained in the normal range by the phosphaturia induced by hyperparathyroidism. In this situation, dietary phosphorus restriction increases calcitriol levels and suppresses parathyroid hormone secretion. As renal failure progresses into late stages, hyperphosphatemia is evident along with low levels of calcitriol and worsening hyperparathyroidism. Phosphorus restriction will not affect calcitriol concentrations, yet parathyroid levels may decline. During long-term dialysis, urinary excretion of phosphorus is usually minimal. Therefore, phosphorus balance is determined primarily by the net amount absorbed by the bowel and the quantity removed during dialytic therapy. Given an adequate diet, no form of conventional dialysis is able to fully compensate for the gastrointestinal absorption of phosphorus. Hence, compounds that bind phosphorus in the bowel are often necessary. With the realization that the use of phosphorus binders containing aluminum leads to aluminum accumulation and its sequelae: osteomalacia, dementia, myopathy, and anemia, other phosphorus binders have been evaluated. Calcium carbonate has been investigated the most thoroughly and is in wide use. It is inexpensive and contains a high percent of elemental calcium. However, it is only modestly potent in the binding of phosphorus, and large doses are often necessary to attain satisfactory control of phosphorus. This may lead to hypercalcemia. One approach to this problem is to decrease the concentration of calcium in the dialysate. Alternatively, a more effective phosphorus binder may be used. Calcium acetate has been shown in acute studies to have twice the binding capacity of phosphorus per calcium absorbed than calcium carbonate. Whether use of this compound decreases the incidence of hypercalcemia is unproven. Calcium citrate increases the gastrointestinal absorption of aluminum and offers no advantage over calcium carbonate. Other compounds, such as calcium ketoacids and calcium alginate, have not been extensively studied and are not generally available. The use of phosphorus binders containing magnesium in conjunction with a dialysate low in magnesium may be efficacious. Large doses of magnesium will cause diarrhea and thus limit its use as a single agent. Reasons for failure to control hyperphosphatemia include poor compliance, improper prescription of binders, poor dissolution rates seen with some generic brands of calcium carbonate, and the presence of severe hyperparathyroidism. Optimal control of serum phosphorus in dialysis patients should always be viewed in the context of adequate nutrition and protein intake.
控制慢性肾功能不全患者体内磷的蓄积对于预防继发性甲状旁腺功能亢进和转移性钙化至关重要。在肾衰竭早期，骨化三醇水平正常，甲状旁腺激素水平升高。甲状旁腺功能亢进引起的磷尿症可使磷水平维持在正常范围。在此情况下，限制饮食中的磷会使骨化三醇水平升高，并抑制甲状旁腺激素分泌。随着肾衰竭进展至晚期，高磷血症明显，同时骨化三醇水平降低，甲状旁腺功能亢进加重。限制磷摄入不会影响骨化三醇浓度，但甲状旁腺激素水平可能会下降。在长期透析过程中，磷的尿排泄通常极少。因此，磷平衡主要取决于肠道吸收的净磷量以及透析治疗中清除的磷量。在饮食充足的情况下，任何形式的传统透析都无法完全代偿肠道对磷的吸收。因此，通常需要使用能在肠道内结合磷的化合物。鉴于含铝磷结合剂的使用会导致铝蓄积及其一系列后果：骨软化症、痴呆、肌病和贫血，人们对其他磷结合剂进行了评估。碳酸钙研究得最为透彻，且广泛应用。它价格低廉，元素钙含量高。然而，它结合磷的能力一般，往往需要大剂量才能达到满意的磷控制效果。这可能导致高钙血症。解决此问题的一种方法是降低透析液中的钙浓度。或者，可使用更有效的磷结合剂。急性研究表明，醋酸钙结合磷的能力是碳酸钙的两倍（每吸收单位钙结合磷的能力）。使用这种化合物是否能降低高钙血症的发生率尚无定论。柠檬酸钙会增加铝的胃肠道吸收，与碳酸钙相比并无优势。其他化合物，如酮酸钙和海藻酸钙，尚未得到广泛研究，也未普遍应用。使用含镁磷结合剂并同时使用低镁透析液可能有效。大剂量镁会导致腹泻，因此限制了其作为单一药物的使用。未能控制高磷血症的原因包括依从性差、磷结合剂处方不当、某些碳酸钙仿制药品牌的溶解率低以及存在严重的甲状旁腺功能亢进。透析患者血清磷的最佳控制应始终在充足营养和蛋白质摄入的背景下考虑。
