Intra-individual fluctuations in alkaline phosphatase predict mortality and CKD progression: insights from a large CKD Cohort

Background Elevated alkaline phosphatase (ALP) levels are associated with mortality. However, the significance of ALP variability, particularly in chronic kidney disease (CKD), has not been well explored. This study examined the associations of baseline ALP and its variability with all-cause mortality and end-stage kidney disease (ESKD) in patients with CKD. Methods This retrospective cohort study analyzed data from tertiary hospitals in Taiwan and Korea (2001–2021). Adults with CKD, defined by at least two estimated glomerular filtration rate (eGFR) values <60 mL/min/1.73 m2 obtained ≥ 3 months apart, were included. ALP variability was measured using the standard deviation (SD), coefficient of variance (CoV), and variance, categorized into quartiles. Cox-proportional hazards model evaluated the associations between ALP indices and mortality and ESKD. Results In the baseline ALP cohort (n = 14 862), higher ALP levels were associated with progressively increased risks of mortality and ESKD, with the highest quartile showing a 1.47-fold higher mortality risk (95% CI 1.32–1.64) than the lowest. In the variability cohort (n = 12 531), greater ALP variability was significantly associated with increased all-cause mortality (SD, aHR: 1.82, 95% CI: 1.61–2.05; CoV, aHR: 1.50, 95% CI: 1.34–1.68; variance, aHR: 1.81, 95% CI: 1.60–2.04) and showed directionally consistent, though attenuated, associations with ESKD risk. Subgroup analysis stratified by hypertension, diabetes, and cardiovascular disease demonstrated consistent association across comorbidities. Conclusion Given the significant impact of ALP levels and their variability on mortality and kidney disease progression, targeted monitoring and stabilization of ALP over time may help improve long-term outcomes in patients with CKD.