Wald Ron, Sarnak Mark J, Tighiouart Hocine, Cheung Alfred K, Levey Andrew S, Eknoyan Garabed, Miskulin Dana C
Division of Nephrology and The Keenan Research Centre in the Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.
Am J Kidney Dis. 2008 Sep;52(3):531-40. doi: 10.1053/j.ajkd.2008.05.020. Epub 2008 Jul 26.
Serum markers of disordered mineral metabolism have been associated with adverse outcomes in patients requiring long-term dialysis therapy. Although the values of these markers often evolve over time, no study has examined the accumulated effects of these abnormalities on important clinical end points.
Retrospective cohort study.
SETTING & PARTICIPANTS: 1,846 prevalent hemodialysis patients randomly assigned in the Hemodialysis (HEMO) Study.
Serum phosphorus, calcium, calcium-phosphorus (Ca x P) product, and intact parathyroid hormone, each analyzed at the time of randomization (baseline), as a standard time-dependent covariate and as a cumulative time-dependent covariate.
All-cause mortality and the composite of all-cause mortality and first cardiac hospitalization.
Cox proportional hazards models.
In all analyses, serum phosphorus level greater than 6 mg/dL was associated with a heightened risk of mortality of approximately 25% compared with phosphorus values of 4.1 to 5 mg/dL. Serum calcium level greater than 11 mg/dL was associated with a 60% greater risk of death, but only when this parameter was analyzed as either a time-dependent or cumulative time-dependent variable. Ca x P product greater than 50 mg(2)/dL(2) was strongly associated with mortality, but only when assessed cumulatively. Similar relationships were observed when phosphorus, calcium, and Ca x P product values were related to the composite end point of all-cause mortality and first cardiac hospitalization. No relationships between baseline, time-dependent, and cumulative time-dependent intact parathyroid hormone levels and the outcomes of interest were observed.
Residual confounding, lack of access to patient information before randomization in the HEMO Study, and concerns regarding generalizability given changes in practice patterns since the completion of the HEMO Study.
Cumulative time-dependent analyses provide a different framework for analyzing the impact of factors that may mediate adverse events in hemodialysis patients. Our findings support maintaining serum phosphorus levels at less than 6 mg/dL, calcium levels at less than 11 mg/dL, and Ca x P product at less than 50 mg(2)/dL(2).
矿物质代谢紊乱的血清标志物与需要长期透析治疗的患者的不良预后相关。尽管这些标志物的值通常会随时间变化，但尚无研究探讨这些异常对重要临床终点的累积影响。
回顾性队列研究。
1846例在血液透析（HEMO）研究中随机分配的维持性血液透析患者。
血清磷、钙、钙磷（Ca×P）乘积以及全段甲状旁腺激素，在随机分组时（基线）进行分析，作为标准的时间依赖性协变量和累积时间依赖性协变量。
全因死亡率以及全因死亡率与首次心脏住院的复合终点。
Cox比例风险模型。
在所有分析中，血清磷水平大于6mg/dL与4.1至5mg/dL的磷值相比，死亡风险升高约25%。血清钙水平大于11mg/dL与死亡风险高60%相关，但仅当该参数作为时间依赖性或累积时间依赖性变量进行分析时。Ca×P乘积大于50mg²/dL²与死亡率密切相关，但仅在累积评估时。当磷、钙和Ca×P乘积值与全因死亡率和首次心脏住院的复合终点相关时，观察到类似的关系。未观察到基线、时间依赖性和累积时间依赖性全段甲状旁腺激素水平与感兴趣的结局之间的关系。
残余混杂因素、HEMO研究中随机分组前无法获取患者信息，以及鉴于HEMO研究完成后实践模式的变化而对普遍性的担忧。
累积时间依赖性分析为分析可能介导血液透析患者不良事件的因素的影响提供了一个不同的框架。我们的研究结果支持将血清磷水平维持在低于6mg/dL，钙水平维持在低于11mg/dL，以及Ca×P乘积维持在低于50mg²/dL²。
