Survival predictability of serum alkaline phosphatase trajectories in Japanese maintenance haemodialysis patients: risk of cardiovascular events and all-cause death.

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https://storage.unitedwebnetwork.com/files/1099/d6273a8115f813405993d7a7d24edd72.pdf

Abstract Title *

Survival predictability of serum alkaline phosphatase trajectories in Japanese maintenance haemodialysis patients: risk of cardiovascular events and all-cause death.

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Co-author 1

Tomohiro Saito saitou1986@med.showa-u.ac.jp Showa University Graduate School of Medicine Department of Nephrology Tokyo Japan *

Co-author 2

Masahide Mizobuchi mizobu@med.showa-u.ac.jp Showa Medical University Fujigaoka Hospital Division of Nephrology, Department of Internal Medicine Yokohama Japan -

Co-author 3

Akane Yamakawa yamakawa.akane@fbri.org The Translational Research Center for Medical Innovation Foundation for Biomedical Research and Innovation Kobe Japan -

Co-author 4

Hidetoshi Ito itohide@med.showa-u.ac.jp Showa Medical University Northern Yokohama Hospital Department of Medicine Yokohama Japan -

Co-author 5

Hiroaki Ogata ogatah@med.showa-u.ac.jp Showa Medical University Northern Yokohama Hospital Department of Medicine Yokohama Japan -

Co-author 6

Tadao Akizawa akizawa@med.showa-u.ac.jp Showa University Graduate School of Medicine Department of Nephrology Tokyo Japan -

Co-author 7

Hirokazu Honda hondah@med.showa-u.ac.jp Showa University Graduate School of Medicine Department of Nephrology Tokyo Japan -

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

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Co-author 15

Introduction

Higher serum alkaline phosphatase (ALP) levels are associated with a poor prognosis in maintenance haemodialysis (MHD). However, longitudinal ALP trajectories are not well described. This study aimed to identify typical ALP trajectory profiles and estimate their associations with cardiovascular events (CVEs) and all-cause death.

Methods

We conducted a post hoc cohort analysis of the LANDMARK trial, a multicenter, randomized, open-label, parallel group study evaluating the effect of phosphate binders on the risk of CVEs in MHD patients with hyperphosphatemia and at risk of vascular calcification. A joint latent class model was used to estimate, in different classed of ALP trajectory, the competing risks of CVEs and all-cause death. Serum intact PTH, C-reactive protein, and phosphate was included in the longitudinal model as fixed effects.

Results

During the follow-up, we gathered 8224 ALP measurements from 1567 patients (median, 6 per patient). Three distinct ALP trajectory profiles were identified: constant, late rise, and early rise. The predominant profile [n=1280 (81.7%)] showed a constant trajectory. The late rise trajectory [n=266 (17.0%)] began at mid-range ALP and increased progressively over time. The early rise trajectory [n=21 (1.3%)] displayed high baseline ALP with a dynamic, non‑linear course. Kaplan–Meier curves stratified by latent class demonstrated clear separation (p=0.018). The constant class the best, the early rise class had the worst survival, with the late rise class in between.

Conclusion

Three temporal ALP patterns with distinct clinical characteristics and outcomes were identified. Most patients exhibited persistently low ALP and had the most favourable prognosis. In contrast, in profiles with rising ALP trajectories, the risks of CVEs and all-cause death began to increase as the ALP trajectory upward. These findings emphasize the importance of monitoring ALP trends over time in MHD patients as a marker of risk.

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