Yamamoto Suguru, Jørgensen Hanne Skou, Zhao Junhui, Karaboyas Angelo, Komaba Hirotaka, Vervloet Marc, Mazzaferro Sandro, Cavalier Etienne, Bieber Brian, Robinson Bruce, Evenepoel Pieter, Fukagawa Masafumi
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium.
Kidney Int Rep. 2024 Jan 11;9(4):863-876. doi: 10.1016/j.ekir.2024.01.002. eCollection 2024 Apr.
Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear.
The analysis included 28,888 patients on HD in 9 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 3 to 7 (2005-2021). The primary exposures of interest were normalized ALP and PTH, which are raw values divided by facility upper normal limit, measured at study enrollment. Cox models were used to estimate hazard ratios of all-cause or CV mortality and any or hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics.
Normalized PTH showed a J-shaped association with all-cause or CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C-reactive protein (CRP), and the use of cinacalcet.
Total ALP is a more robust exposure of adverse outcomes than PTH in patients on HD. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of (SHPT).
继发性甲状旁腺功能亢进（SHPT）增加了血液透析（HD）患者骨折和心血管（CV）疾病的风险。甲状旁腺激素（PTH）与预后之间的关系并不一致，这可能是由于骨骼对PTH的反应性存在差异。KDIGO指南建议监测总碱性磷酸酶（ALP），但ALP与PTH在矿物质和骨代谢紊乱（MBD）管理中的作用尚不清楚。
该分析纳入了透析结果和实践模式研究（DOPPS）第3至7阶段（2005 - 2021年）9个国家的28,888例HD患者。感兴趣的主要暴露因素是标准化ALP和PTH，即研究入组时测量的原始值除以机构正常上限值。使用Cox模型估计全因或CV死亡率以及任何骨折或髋部骨折的风险比，并对潜在混杂因素进行调整。采用线性混合模型，对潜在混杂因素进行调整，以研究标准化ALP水平与患者特征之间的关系。
标准化PTH与全因或CV死亡率呈J形关联，与骨折呈弱线性关联。相比之下，标准化ALP与所有结局均呈强关联。在控制PTH后，与较高ALP水平相关的因素包括黑人种族、透析时间较长、糖尿病、低钙血症、低磷血症、C反应蛋白（CRP）升高以及使用西那卡塞。
在HD患者中，总ALP比PTH更能有力地反映不良结局。PTH反应性受种族、原发性肾脏疾病、合并症以及矿物质代谢和治疗的影响。我们的结果表明，在考虑SHPT的后果时，评估靶器官反应而非仅评估PTH可能是有用的。
