PLoS One. 2026 Jun 18;21(6):e0351946. doi: 10.1371/journal.pone.0351946. eCollection 2026.
ABSTRACT
BACKGROUND: Cardiovascular-Kidney-Metabolic (CKM) syndrome involves disordered mineralization processes. Herein, we investigated the serum alkaline phosphatase (ALP), calcium, and phosphorus across CKM stages.
METHODS: This study analyzed 15,233 eligible participants in National Health and Nutrition Examination Survey (2009-2018) using survey-weighted multinomial logistic regression to assess associations of ALP, calcium, and phosphorus. Restricted cubic splines assessed non-linear relationships, while Cox models examined mortality risks. Two-sample Mendelian randomization (MR) explored causal relationships.
RESULTS: Relative risk ratios (RRRs) and 95% confidence intervals (95% CI) were calculated with multinomial logistic regression. Compared with stage 0, ALP was positively associated with the likelihood of being classified into stage 2 (RRR, 1.23[95% CI, 1.11-1.37]), stage 3 (RRR, 1.99 [95% CI, 1.48-2.67]), stage 4a (RRR, 1.29 [95% CI, 1.14-1.46]), stage 4b (RRR, 1.35 [95% CI, 1.16-1.58]). Per mg/dL increase in serum calcium levels was associated with a higher likelihood of being classified into stages 2 (RRR = 2.13, 95% CI: 1.55-2.94) and CKM stage 4, while per mg/dL increase in serum phosphorus was associated with stage 3 classification (RRR = 2.85, 95% CI: 1.77-4.59) and the results remained consistent after standardizing the markers using z-scores. ALP's 4th quartile was associated with the highest mortality risks (CKM-cause hazard ratio = 2.20; all-cause hazard ratio = 2.15). MR analysis indicated potential causal effects of ALP on cardiovascular disease and of chronic kidney disease on ALP.
CONCLUSIONS: ALP demonstrates consistent associations with all CKM stages. These findings indicate that ALP-related mechanisms need further exploration.
PMID:42313881 | DOI:10.1371/journal.pone.0351946