Maruyama Yukio, Nakashima Akio, Abe Masanori, Hanafusa Norio, Nakai Shigeru, Yokoo Takashi
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan.
Kidney360. 2025 Mar 1;6(3):400-411. doi: 10.34067/KID.0000000656. Epub 2024 Nov 26.
In the lower-parathyroid hormone (PTH) group, associations between serum alkaline phosphatase (ALP) and all-cause mortality were positive and linear. In the higher-PTH group, lower serum ALP tended to have higher risk than those with intermediate serum ALP. Serum ALP was independently and linearly associated with new hip fracture regardless of intact PTH level.
Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of CKD–mineral bone disorder because of associations with poor outcomes among patients on dialysis. However, such associations may have changed with several advances in the management of CKD–mineral bone disorder over the past decade.
Baseline data of 241,670 patients on dialysis (mean age, 69±12 years; male, 65.9%; median dialysis duration, 68 months) were extracted from a nationwide dialysis registry in Japan at the end of 2019. Outcomes, including all-cause and cardiovascular (CV) mortality and hip fracture, were evaluated using the registry at the end of 2020 and 2021. All-cause mortality was assessed using Cox regression analysis, whereas CV mortality and new hip fracture were assessed using competing-risks regression analysis. Multiple imputations for missing values were performed.
Within the 2-year study period, a total of 40,449 patients (16.7%) died, including 13,562 CV deaths (5.6%). Of the 168,836 patients with no history of hip fracture at the end of 2019, 4136 (2.4%) suffered hip fracture within 2 years. Higher serum ALP was independently associated with higher all-cause and CV mortality and new hip fracture, but the association with CV mortality was marginal (hazard ratio, 1.21; 95% confidence interval [CI], 1.18 to 1.24; subhazard ratio, 1.07; 95% CI, 1.03 to 1.12 and subhazard ratio, 1.28, 95% CI, 1.19 to 1.38, respectively). There is a linear association between serum ALP and all-cause mortality among the lower parathyroid hormone (PTH) group, whereas lower serum ALP tended to have higher all-cause mortality than intermediate serum ALP among patients in the higher PTH group.
Higher serum ALP was independently and linearly associated with higher all-cause and CV mortality and new hip fracture in Japanese patients on dialysis. Higher serum ALP and higher intact PTH were synergistic in increasing all-cause and CV mortality but were not associated with new hip fracture.
在甲状旁腺激素（PTH）水平较低的组中，血清碱性磷酸酶（ALP）与全因死亡率之间呈正相关且呈线性关系。在PTH水平较高的组中，血清ALP较低者的风险往往高于血清ALP处于中等水平者。无论完整PTH水平如何，血清ALP均与新发髋部骨折独立且呈线性相关。
由于血清碱性磷酸酶（ALP）与透析患者的不良预后相关，因此在慢性肾脏病 - 矿物质和骨异常（CKD - MBD）的管理中建议监测ALP。然而，在过去十年中，随着CKD - MBD管理方面的多项进展，这种关联可能已经发生了变化。
2019年底从日本全国性透析登记处提取了241,670例透析患者的基线数据（平均年龄69±12岁；男性占65.9%；透析持续时间中位数为68个月）。使用2020年底和2021年底的登记处数据评估包括全因和心血管（CV）死亡率以及髋部骨折在内的结局。全因死亡率采用Cox回归分析评估，而CV死亡率和新发髋部骨折采用竞争风险回归分析评估。对缺失值进行了多次插补。
在2年的研究期内，共有40,449例患者（16.7%）死亡，其中包括13,562例CV死亡（5.6%）。在2019年底无髋部骨折病史的168,836例患者中，有4136例（2.4%）在2年内发生了髋部骨折。较高的血清ALP与较高的全因和CV死亡率以及新发髋部骨折独立相关，但与CV死亡率的关联较弱（风险比，1.21；95%置信区间[CI]，1.18至1.24；亚风险比，1.07；95%CI，1.03至1.12；亚风险比，1.28，95%CI，1.19至1.38）。在甲状旁腺激素（PTH）水平较低的组中，血清ALP与全因死亡率之间存在线性关联，而在PTH水平较高的组中，血清ALP较低者的全因死亡率往往高于血清ALP处于中等水平者。
在日本透析患者中，较高的血清ALP与较高的全因和CV死亡率以及新发髋部骨折独立且呈线性相关。较高的血清ALP和较高的完整PTH在增加全因和CV死亡率方面具有协同作用，但与新发髋部骨折无关。
