Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Clin J Am Soc Nephrol. 2012 May;7(5):810-9. doi: 10.2215/CJN.08680811. Epub 2012 Feb 23.
Hyperphosphatemia, vitamin D deficiency, hyperparathyroidism, and high serum fibroblast growth factor 23 (FGF23) levels, when studied separately, were found to predict the progression of CKD. However, studies with simultaneous measurement of mineral bone disorder (MBD)-related factors were scarce. This study aimed to identify factors predicting renal outcome independent of other factors.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective cohort study of 738 Japanese predialysis outpatients in the nephrology departments of two hospitals. The outcome was defined as a doubling of serum creatinine or initiation of dialysis.
Mean estimated GFR (eGFR) was 35 ml/min per 1.73 m(2). At enrollment, the increase in intact FGF23 with decreasing eGFR was the earliest among changes in MBD-related factors, followed by 1,25-dihydroxyvitamin D decrease, parathyroid hormone increase, and phosphate increase. During a median duration of 4.4 years, 213 patients reached the endpoint. In a multivariable Cox model, high FGF23 and low 25-hydroxyvitamin D (25D) levels were the only MBD-related factors associated with a higher risk of renal endpoint (adjusted hazard ratio [95% confidence interval] per unit change of log FGF23 and 10 ng/ml of 25D: 1.83 [1.28-2.61] and 0.61 [0.41-0.90], respectively). There was no significant interaction between 25D and FGF23 (P=0.11). Active vitamin D therapy, serum phosphate, 1,25-dihydroxyvitamin D, and parathyroid hormone levels were not related to the renal endpoint. Treating death as a competing risk or multiple imputation for missing values yielded similar results.
Combined use of two markers is useful for the risk stratification of renal outcome.
分别研究发现，高磷血症、维生素 D 缺乏、甲状旁腺功能亢进和高血清成纤维细胞生长因子 23（FGF23）水平与 CKD 的进展相关。然而，关于同时测量矿物质骨代谢紊乱（MBD）相关因素的研究却很少。本研究旨在寻找与其他因素无关的预测肾脏结局的因素。
设计、地点、参与者和测量方法：这是一项前瞻性队列研究，纳入了两家医院肾病科的 738 例日本透析前门诊患者。研究的终点定义为血清肌酐倍增或开始透析。
平均估算肾小球滤过率（eGFR）为 35ml/min/1.73m2。在入组时，与 MBD 相关因素的变化相比，完整 FGF23 随 eGFR 下降而增加的速度最快，其次是 1,25-二羟维生素 D 下降、甲状旁腺激素增加和磷酸盐增加。在中位时间为 4.4 年的随访期间，213 例患者达到了终点。在多变量 Cox 模型中，高 FGF23 和低 25-羟维生素 D（25D）水平是唯一与肾脏终点风险升高相关的 MBD 相关因素（log FGF23 每单位变化和 25D 每增加 10ng/ml 的校正危险比[95%置信区间]：1.83[1.28-2.61]和 0.61[0.41-0.90]）。25D 和 FGF23 之间无显著交互作用（P=0.11）。活性维生素 D 治疗、血清磷酸盐、1,25-二羟维生素 D 和甲状旁腺激素水平与肾脏终点无关。将死亡视为竞争风险或对缺失值进行多重插补也得到了相似的结果。
联合使用这两个标志物有助于预测肾脏结局的风险分层。
