Distinct longitudinal trajectories of alkaline phosphatase and parathyroid hormone at dialysis initiation predict mortality in incident hemodialysis patients.

BACKGROUND

Chronic kidney disease (CKD)-mineral and bone disorder (MBD) contributes to fractures, cardiovascular events, and mortality in patients receiving maintenance hemodialysis (MHD). The longitudinal patterns of the CKD-MBD biomarkers parathyroid hormone (PTH) and alkaline phosphatase (ALP), as well as their prognostic value, remain uncertain.

METHODS

We retrospectively identified patients initiating MHD between 2004 and 2012 using linked medical records and Taiwan National Health Insurance Research Database. Two-year serial ALP (n = 447) and PTH (n = 338) measurements were analyzed using group-based trajectory modeling to characterize longitudinal patterns. A landmark design was applied for outcome analysis, and multivariable Cox models were used to assess associations between trajectory group membership and subsequent clinical outcomes, including fractures, major adverse cardiovascular events, cardiovascular death, and all-cause mortality.

RESULTS

Three distinct trajectories were identified for both ALP and PTH, and remained stable from MHD initiation. ALP trajectories were labeled as low-normal, high-normal, and high based on median levels relative to the reference range, while PTH trajectories were labeled as below-target, within-lower-target, and within-upper-target according to KDIGO-recommended target ranges for patients receiving MHD; these groups demonstrated statistically significant differences in median ALP and PTH levels across trajectories. A high-normal ALP trajectory was independently associated with cardiovascular death (adjusted HR, 8.44; 95% CI, 1.78-39.96; P = 0.0072) and all-cause mortality (adjusted HR, 1.54; 95% CI, 1.15-2.06; P = 0.0034). A below-target PTH trajectory was associated with a higher crude risk of all-cause mortality compared with other trajectory patterns.

CONCLUSIONS

ALP and PTH trajectories are identifiable early after HD initiation and reflect distinct risk profiles. These findings support the clinical value of longitudinal monitoring from the early dialysis period and highlight the importance of avoiding PTH oversuppression to improve risk stratification and management. Future large-scale prospective studies are needed to clarify subtle longitudinal changes in ALP and PTH and their associations with outcomes.