AUTHOR=Li Jian-Chun , Huang Shi-Tao , Feng Fei , Wang Lin-Jun , Chen Ting-Ting , Li Min , Liu Li-Ping TITLE=Relationship between low molecular weight heparin calcium therapy and prognosis in severe acute kidney injury in sepsis: Mendelian randomized analysis and retrospective study JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1389354 DOI=10.3389/fphar.2024.1389354 ISSN=1663-9812 ABSTRACT=Background

Sepsis-associated acute kidney injury (SA-AKI) poses an independent risk for mortality due to the absence of highly sensitive biomarkers and a specific treatment plan.

Objective

Investigate the association between low molecular weight heparin (LMWH) calcium therapy and prognosis in critically ill SA-AKI patients, and assess the causal relationship through Mendelian randomization (MR) analysis.

Methods

A single-center, retrospective, cross-sectional study included 90 SA-AKI patients and 30 septic patients without acute kidney injury (AKI) from the intensive care unit (ICU) of the First Hospital of Lanzhou University. SA-AKI patients were categorized into control or LMWH groups based on LMWH calcium usage. Primary outcome was renal function recovery, with secondary outcomes including 28-day mortality, ICU stay length, number of renal replacement therapy (RRT) recipients, and 90-day survival. MR and related sensitivity analyses explored causal effects.

Results

The combination of heparin-binding protein (HBP), heparanase (HPA), and neutrophil gelatinase-associated lipocalin (NGAL) demonstrated high diagnostic value for SA-AKI. MR analysis suggested a potential causal link between gene-predicted HBP and AKI (OR: 1.369, 95%CI: 1.040–1.801, p = 0.024). In the retrospective study, LMWH-treated patients exhibited improved renal function, reduced levels of HPA, HBP, Syndecan-1, and inflammation, along with enhanced immune function compared to controls. However, LMWH did not impact 28-day mortality, 90-day survival, or ICU stay length.

Conclusion

LMWH could enhance renal function in SA-AKI patients. MR analysis supports this causal link, underscoring the need for further validation in randomized controlled trials.