Higher Serum Alkaline Phosphatase Is a Risk Factor of Death and Fracture: A Nationwide Cohort Study of Japanese Patients on Dialysis

Key PointsIn 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.BackgroundMonitoring 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.MethodsBaseline 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.ResultsWithin 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.ConclusionsHigher 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.