Lorenzo Sellares Víctor, Torres Ramírez Armando
Nephrology Service, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
Drugs Aging. 2004;21(3):153-65. doi: 10.2165/00002512-200421030-00002.
Phosphorus control remains a relevant clinical problem in dialysis patients. With age, however, serum phosphorus level decreases significantly because of a spontaneous decrease in protein intake. Older patients usually need lower doses of phosphorus binders. Nevertheless, hyperphosphataemia is observed in a quarter of patients aged >65 years. Phosphorus retention is related to an imbalance between phosphorus intake and removal by dialysis, and is usually aggravated when vitamin D analogues are employed. Hyperphosphataemia induces secondary hyperparathyroidism and the development of osteitis fibrosa. Recent publications describe an association between phosphorus retention and increased calcium and phosphorus product (Ca2+ x P), with significant progression of tissue calcification and higher mortality risk. Dietary intervention, phosphorus removal during dialysis and phosphorus binders are current methods for the management of hyperphosphataemia. However, the phosphorus removed by standard haemodialysis is insufficient to achieve a neutral phosphorus balance when protein intake is >50 g/day. Additional protein restriction may impose the risk of a negative protein balance. More frequent dialysis may help to control resistant hyperphosphataemia. Phosphorus binders constitute the mainstay of serum phosphorus level control in end-stage renal disease patients. Aluminium-based phosphorus binders, associated with toxic effects, have largely been substituted by calcium-based phosphorus binders. However, widespread use of calcium-based phosphorus binders has evidenced the frequent appearance of hypercalcaemia and long-term progressive cardiovascular calcification. Sevelamer, a relatively new phosphorus binder, has proved efficacious in lowering serum phosphorus and parathyroid hormone (PTH) levels without inducing hypercalcaemia. Furthermore, several investigators have reported that sevelamer may prevent progression of coronary calcification. However, its efficacy in severe cases of hyperphosphataemia remains to be confirmed in large series. There are no specific guidelines for phosphorus control in the elderly. Until more information is available, levels of mineral metabolites should be targeted in the same range as those recommended for the general population on dialysis (calcium 8.7-10.2 mg/dL, phosphorus 3.5-5.5 mg/dL and Ca2+ x P 50-55 mg2/dL2). PTH values over 120 ng/L help to avoid adynamic bone disease. Since elderly patients have a higher incidence of adynamic bone (which buffers less calcium) and vascular calcification, sevelamer should be the phosphorus binder of choice in this population; but sevelamer is costly and its long-term efficacy has not been definitively validated. Patients with low normal levels of calcium may receive calcium-based phosphorus binders with little risk. Patients with low values of PTH and high normal calcium should receive sevelamer. Tailored combinations of calcium-based phosphorus binders and sevelamer should be considered, and calcium dialysate concentration adjusted accordingly.
磷控制仍然是透析患者中一个重要的临床问题。然而，随着年龄增长，由于蛋白质摄入量自发减少，血清磷水平会显著下降。老年患者通常需要较低剂量的磷结合剂。尽管如此，在四分之一的65岁以上患者中仍观察到高磷血症。磷潴留与磷摄入和透析清除之间的失衡有关，并且在使用维生素D类似物时通常会加重。高磷血症会诱发继发性甲状旁腺功能亢进和纤维性骨炎的发展。最近的出版物描述了磷潴留与钙磷乘积（Ca2+×P）增加之间的关联，伴有组织钙化的显著进展和更高的死亡风险。饮食干预、透析过程中的磷清除和磷结合剂是目前治疗高磷血症的方法。然而，当蛋白质摄入量>50克/天时，标准血液透析清除的磷不足以实现磷的中性平衡。额外的蛋白质限制可能会带来蛋白质负平衡的风险。更频繁的透析可能有助于控制难治性高磷血症。磷结合剂是终末期肾病患者血清磷水平控制的主要手段。与毒性作用相关的铝基磷结合剂已 largely 被钙基磷结合剂所取代。然而，钙基磷结合剂的广泛使用已证明高钙血症频繁出现以及长期进行性心血管钙化。司维拉姆是一种相对较新的磷结合剂，已被证明在降低血清磷和甲状旁腺激素（PTH）水平方面有效，且不会诱发高钙血症。此外，一些研究人员报告称司维拉姆可能预防冠状动脉钙化的进展。然而，其在严重高磷血症病例中的疗效仍有待在大样本系列中得到证实。对于老年人的磷控制没有具体指南。在获得更多信息之前，矿物质代谢物水平的目标应与一般透析人群推荐的范围相同（钙8.7 - 10.2毫克/分升，磷3.5 - 5.5毫克/分升，Ca2+×P 50 - 55毫克²/分升²）。PTH值超过120纳克/升有助于避免动力缺失性骨病。由于老年患者动力缺失性骨（缓冲钙的能力较低）和血管钙化的发生率较高，司维拉姆应是该人群的首选磷结合剂；但司维拉姆成本高昂且其长期疗效尚未得到明确验证。钙水平略低的患者使用钙基磷结合剂风险较小。PTH值低且钙水平略高的患者应使用司维拉姆。应考虑钙基磷结合剂和司维拉姆的定制组合，并相应调整钙透析液浓度。
