Higher Serum Alkaline Phosphatase is Risk for Death and Fracture: A Nationwide Cohort Study of Japanese Dialysis Patients.

Abstract

Background: Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of chronic kidney disease (CKD)-mineral bone disorder (MBD) because of associations with poor outcome among dialysis patients. However, such associations may have changed with several advances in the management of CKD-MBD over the last decade.

Methods: Baseline data for 241,670 dialysis patients (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 imputation for missing values was performed.

Results: Within the 2-year study period, a total of 40,449 patients (16.7%) died, including 13,562 (5.6%) CV deaths. Of the 168,836 patients with no history of hip fracture at the end of 2019, 4,136 (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 [HR] 1.21, 95% confidence interval [CI] 1.18-1.24; sub-HR [SHR] 1.07, 95%CI 1.03-1.12; and SHR 1.28, 95%CI 1.19-1.38, respectively). There is a linier 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.

Conclusions: Higher serum ALP was independently and linearly associated with higher all-cause and CV mortality and new hip fracture in Japanese dialysis patients. Higher serum ALP and higher intact PTH were synergistic in increasing all-cause and CV mortality but not with new hip fracture.