Shinaberger Christian S, Kopple Joel D, Kovesdy Csaba P, McAllister Charles J, van Wyck David, Greenland Sander, Kalantar-Zadeh Kamyar
Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90509-2910, USA.
Clin J Am Soc Nephrol. 2008 Nov;3(6):1769-76. doi: 10.2215/CJN.01760408. Epub 2008 Aug 13.
Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients; however, patients with higher serum parathyroid hormone (PTH), indicative of a more severe secondary hyperparathyroidism and higher death risk, are usually given higher VDRA dosages, which can lead to confounding by medical indication and attenuated survival advantage of high VDRA dosages. It was hypothesized that the ratio of the administered paricalcitol dosage to serum PTH level discloses better the underlying dosage-survival association.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The 3-yr mortality predictability of the administered paricalcitol during the first 3 mo of the cohort divided by averaged serum intact PTH during the same period was examined in 34,307 MHD patients from all DaVita dialysis clinics across the United States using Cox regression.
MHD patients were 60.8 +/- 15.4 yr of age and included 47% women, 34% black patients, and 47% patients with diabetes. Initially, the ratio of paricalcitol (mircrog/wk) to PTH (pg/ml) was divided into four groups: 0 (reference), 1 to <30, 30 to <60, and >60 x 10(-3). Unadjusted, case mix-adjusted (demographics, comorbidity, and Kt/V), and malnutrition-inflammation complex syndrome-adjusted models, the death rate ratio for the paricalcitol/PTH index groups, were 0.99, 0.95, and 0.92. Restricted cubic splines analyses were consistent with a linear relation.
Higher weekly paricalcitol dosage per each unit of serum PTH seems to have an incremental association with greater survival in MHD patients. The observed dosage-response phenomenon needs to be confirmed in clinical trials.
多项观察性研究表明,包括帕立骨化醇在内的维生素D受体激活剂(VDRA)与维持性血液透析(MHD)患者的更高生存率相关;然而,血清甲状旁腺激素(PTH)水平较高的患者,提示继发性甲状旁腺功能亢进更严重且死亡风险更高,通常会给予更高剂量的VDRA,这可能导致医疗指征的混杂以及高剂量VDRA生存优势的减弱。据推测,所给予的帕立骨化醇剂量与血清PTH水平的比值能更好地揭示潜在的剂量 - 生存关联。
设计、设置、参与者与测量:在美国各地所有达维塔透析诊所的34307例MHD患者中,使用Cox回归分析了队列前3个月内给予的帕立骨化醇剂量除以同期平均血清完整PTH的3年死亡率预测能力。
MHD患者年龄为60.8±15.4岁,其中女性占47%,黑人患者占34%,糖尿病患者占47%。最初,帕立骨化醇(微克/周)与PTH(皮克/毫升)的比值分为四组:0(参照组)、1至<30、30至<60以及>60×10⁻³。在未调整、病例组合调整(人口统计学、合并症和Kt/V)以及营养不良 - 炎症综合征调整模型中,帕立骨化醇/PTH指数组的死亡率比值分别为0.99、0.95和0.92。受限立方样条分析与线性关系一致。
每单位血清PTH的每周帕立骨化醇剂量越高,似乎与MHD患者的更高生存率呈递增关联。观察到的剂量 - 反应现象需要在临床试验中得到证实。