# Plasma Insulin-Like Growth Factor-Binding Protein-2 Levels Predict Severe Septic Acute Kidney Injury: A Mendelian Randomization Analysis

## TL;DR

This study shows that high IGFBP-2 levels in blood can predict severe kidney injury in sepsis patients, but there is no direct cause-and-effect link.

## Contribution

The study introduces IGFBP-2 as a potential early biomarker for sepsis-induced kidney injury using a Mendelian randomization approach.

## Key findings

- IGFBP-2 alone predicted SA-AKI with high sensitivity and specificity.
- Combining IGFBP-2 with clinical scores improved prediction accuracy.
- MR analysis found no causal link between IGFBP-2 and AKI.

## Abstract

Background: Sepsis-associated acute kidney injury (SA-AKI) currently lacks highly sensitive biomarkers for early detection, resulting in delayed identification and intervention during its early stages and an independent risk of death.

Objective: This study aimed to investigate the relationship between insulin-like growth factor-binding protein-2 (IGFBP-2) levels and the occurrence of sepsis-induced kidney injury and to evaluate the causal relationship between the two through Mendelian randomization (MR) analysis.

Methods: This study employed a single-center, prospective cohort design involving 79 sepsis patients from the Intensive Care Unit (ICU) at the First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China. The patients were divided into two groups, the SA-AKI group and the non-SA-AKI group, on the basis of whether they developed SA-AKI. The primary endpoint was whether SA-AKI occurred within 48 hours of admission. MR and sensitivity analyses were conducted to explore the causal relationships.

Results: The IGFBP-2 level had high diagnostic value for the prediction of SA-AKI. Receiver operating characteristic (ROC) curve analysis revealed that IGFBP-2 alone predicted SA-AKI, with an area under the curve (AUC) of 0.8994, a cut-off value of 709.004, a sensitivity of 88.64%, and a specificity of 85.71%. The combined prediction of the IGFBP-2 score, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and use of vasopressors had an AUC of 0.9604, a sensitivity of 93.18%, and a specificity of 82.86%. MR analysis revealed no causal relationship between genetically predicted IGFBP-2 levels and AKI (OR: 1.1507, 95% CI: 0.88-1.50, p = 0.2995).

Conclusion: Plasma IGFBP-2 levels can predict the occurrence of SA-AKI in sepsis patients. However, MR analysis suggests that there is no direct causal relationship between plasma IGFBP-2 levels and septic kidney injury, and the underlying mechanisms need to be further investigated in randomized controlled trials.