The relationship between serum alkaline phosphatase levels and sepsis: observational and Mendelian randomization studies

Abstract

Aim: There is no definitive evidence to establish a causal relationship between elevated serum alkaline phosphatase (ALP) levels and sepsis susceptibility. This study employed observational and Mendelian randomization (MR) studies to investigate their potential correlation.

Methods: This observational study used data from the eICU Collaborative Research Database (eICU-CRD) and included adult patients who were admitted to the ICU for a single episode, with an ICU stay of ≥ 24 h, and serum ALP records obtained within 24 hours of admission. Based on three quantiles of ALP, participants were divided into three groups (Units/L): ALP ≤ 59, 60 ≤ ALP ≤ 86, and ALP ≥ 87. Multivariate logistic regression (MLR) explored the association between serum ALP levels and sepsis susceptibility in the general population and subgroups categorized by sex, age, blood lactate, and APACHE IV scores. Meanwhile, this study utilized genome-wide association studies (GWAS) data of serum ALP levels (Neale lab, n = 13,586,006) and sepsis (UK Biobank, n = 12,243,539) to conduct MR analysis to validate their causal relationship by the inverse variance weighted (IVW) method.

Results: The observational study comprised 4,458 patients. The sepsis susceptibility of the three groups was 11.1%, 12.5%, and 17.4%, respectively. MLR analysis revealed that sepsis susceptibility of the ALP ≥ 87 group was 1.748 times higher than the ALP ≤ 59 group (OR = 1.748, 95%CI: 1.399-2.183). There was a consistent correlation between them in sex, age, blood lactate, and the APACHE IV scores subgroup. MR study demonstrated a causal association between them (OR = 1.005, 95%CI: 1.002-1.008).

Conclusions: Elevated serum ALP levels are significantly associated with sepsis susceptibility, and there is a causal relationship between them.

Keywords

Alkaline phosphatase / sepsis / observational study / Mendelian randomization study / biomarker

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