Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients
Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients
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DOI：
10.1038/sj.ki.5001514
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发表时间：
2006-08-01
影响因子：
19.6
通讯作者：
Kopple, J. D.
中科院分区：
文献类型：
--
作者：
Kalantar-Zadeh, K.;Kuwae, N.;Kopple, J. D.
虽然肾性骨营养不良和维生素D类似物可能与维持性血液透析（MHD）患者的生存率有关，但大多数研究都检查了基线值与生存率之间的相关性，而没有考虑临床和实验室指标随时间的变化。我们使用重复测量的时间依赖性考克斯模型和仅使用基线值的固定协变量考克斯模型，在美国所有DaVita透析诊所的58058例MHD患者的2年（2001年7月至2003年6月）队列中检查了生存率和季度实验室值之间的相关性，并给予帕立骨化醇。尽管在所有模型中高钙血症和高磷血症都是较高死亡风险的可靠预测因子，但血清钙与死亡率之间的相关性在随时间变化的模型中是不同的。基线钙和磷值的变化超过肾脏疾病结局质量倡议推荐的目标与死亡率增加相关。高血清甲状旁腺激素和死亡风险增加之间的关系被MHD患者的病例组合特征所掩盖。随时间变化的血清碱性磷酸酶与死亡率呈递增相关。在时变模型中，给予任何剂量的帕立骨化醇均与生存期改善相关。控制营养标志物可能会引入过度调整偏倚，因为它们与骨营养不良替代物具有很强的共线性。尽管时间依赖性和固定协变量考克斯模型导致骨营养不良指标与生存率之间存在相似的相关性，但两种模型之间存在细微但可能具有临床相关性的差异，可能是因为固定模型不能解释骨营养不良指标随时间的变化和药物剂量的变化。
Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year ( July 2001-June 2003) cohort of 58 058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.