Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Curr Opin Nephrol Hypertens. 2018 Jul;27(4):258-267. doi: 10.1097/MNH.0000000000000417.
Treatment of mineral metabolism is a mainstay of dialysis care including some of its most widely used and costly pharmaceuticals. Although many mineral metabolites are associated with increased risk of mortality, cardiovascular disease, and other morbidities, few clinical trials are available to guide therapy and most focus on single drug approaches. In practice, providers manage many aspects of mineral metabolism simultaneously in integrated treatment approaches that incorporate multiple agents and changes in the dialysis prescription. The present review discusses the rationale and existing evidence for evaluating integrated, as opposed to single drug, approaches in mineral metabolism.
Drugs used to treat mineral metabolism have numerous, and sometimes, opposing effects on biochemical risk factors, such as fibroblast growth factor 23 (FGF23), calcium, and phosphorus. Although vitamin D sterols raise these risk markers when lowering parathyroid hormone (PTH), calcimimetics lower them. Trials demonstrate that combined approaches best 'normalize' the mineral metabolism axis in end-stage renal disease (ESRD). Observations embedded within major trials of calcimimetics reveal that adjustment of calcium-based binders and dialysate calcium is a common approach to adverse effects of these drugs with some initial, but inconclusive, evidence that these co-interventions may impact outcomes.
The multiple, and often opposing, biochemical effects of many mineral metabolism drugs provides a strong rationale for studying integrated management strategies that consider combinations of drugs and co-interventions as a whole. This remains a current gap in the field with opportunities for clinical trials.
矿物质代谢的治疗是透析治疗的基础，包括一些最广泛使用和最昂贵的药物。尽管许多矿物质代谢物与死亡率、心血管疾病和其他发病率增加有关，但可用于指导治疗的临床试验很少，而且大多数临床试验都集中在单一药物方法上。在实践中，提供者同时管理矿物质代谢的许多方面，采用综合治疗方法，包括多种药物和透析处方的改变。本综述讨论了评估矿物质代谢中综合治疗方法与单一药物治疗方法的原理和现有证据。
用于治疗矿物质代谢的药物对生化风险因素有许多、有时甚至是相反的影响，如成纤维细胞生长因子 23（FGF23）、钙和磷。虽然维生素 D 甾醇在降低甲状旁腺激素（PTH）时会升高这些风险标志物，但钙敏感受体激动剂会降低它们。试验表明，联合方法最能“使终末期肾病（ESRD）患者的矿物质代谢轴正常化”。在钙敏感受体激动剂的主要试验中观察到，调整钙基结合剂和透析液钙是处理这些药物不良反应的常见方法，虽然有一些初步但尚无定论的证据表明这些联合干预可能会影响结果。
许多矿物质代谢药物的多种且常常相互矛盾的生化作用为研究综合管理策略提供了强有力的理由，这些策略将药物组合和联合干预作为一个整体来考虑。这仍然是该领域的一个当前差距，有机会进行临床试验。
