GDF15: Review of its Biochemistry and Role as a Marker for Preoperative Risk, Surgical Stress, and Postoperative...

The perioperative period poses significant physiological challenges, often leading to complications such as organ injury and systemic inflammation, which impact surgical outcomes. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine within the TGF-β superfamily, has emerged as a promising biomarker and therapeutic target in perioperative medicine. This review synthesizes current evidence on GDF15's multifaceted roles across various surgical contexts. As a predictive biomarker, GDF15 demonstrates superior accuracy in stratifying risks for postoperative complications, particularly in cardiovascular and transplant surgeries, outperforming traditional markers like CRP and BNP. Mechanistically, GDF15 contributes to organ protection by modulating inflammation, mitochondrial function, and tissue repair pathways. In bariatric surgery, GDF15 mediates sustained metabolic benefits, while in sepsis, it reflects mitochondrial stress and immune dysfunction. Despite its potential, challenges such as context-dependent pleiotropy, assay variability, and unresolved mechanistic pathways hinder clinical translation. Future directions include advancing receptor-specific therapies, standardizing assays, and integrating GDF15 into AI-driven predictive models. By decoding its complex biology, GDF15 could revolutionize personalized perioperative care, enhancing surgical resilience and outcomes across diverse clinical scenarios.