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논문분류	춘계학술대회 초록집
제목	Plasma Levels of Growth Differentiation Factor 15 and Adverse Kidney Outcomes
저자	Hee Byung Koh
출판정보	2025; 2025(1):
키워드	GDF-15, Mendelian randomization, Proteomics, CKD
초록	Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine, is implicated in adverse outcomes of cardiovascular disease, diabetes, and malignancies, highlighting its potential as a prognostic marker. However, its association with chronic kidney disease (CKD) development and its underlying mechanisms remain unclear. We aimed to investigate the association between baseline plasma GDF-15 levels and incident CKD, explore potential mechanisms using proteomics, and assess their causal relationship with kidney function using Mendelian randomization (MR). We analyzed 31,965 UK Biobank participants without pre-existing CKD. The primary outcome was incident CKD, defined by diagnostic codes or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (eGFR-based CKD). Proteomics-based mediation and protein-protein interaction analyses were performed to identify potential mediators linking GDF-15 to CKD. Additionally, bidirectional two-sample MR analyses were conducted using genome-wide association study summary statistics to evaluate the causal relationship between GDF-15 and eGFR. In multivariable cause-specific analyses, higher GDF-15 levels were significantly associated with an increased risk of CKD (adjusted HR: Q2, 1.05 [0.87-1.26]; Q3, 1.21 [1.01-1.45]; Q4, 1.87 [1.56-2.26] vs. Q1; P-for-trend <0.001). Similar results were observed with eGFR-based CKD outcome (adjusted HR: Q2: 1.99 [1.22-3.24]; Q3: 2.82 [1.76-4.50]; Q4: 4.70 [2.95-7.48] vs. Q1; P-for-trend <0.001). Proteomics-based mediation analysis identified proteins associated with TNF receptor superfamily signaling, extracellular matrix organization, and immune cell chemotaxis as mediators. MR analysis demonstrated a significant causal association between genetically predicted higher GDF-15 levels and higher eGFR (IVW coefficient: 0.003; 95% CI: 0.001-0.004; P = 0.004). Conversely, higher genetically predicted eGFR was associated with lower GDF-15 levels (IVW coefficient: -1.238; 95% CI: -1.591 to -0.886; P < 0.001). This study provides evidence supporting the role of GDF-15 as a prognostic biomarker for CKD, suggesting its causal protective effect on kidney function. Further studies are required to explore the mechanistic pathways and therapeutic implications of GDF-15 in kidney disease.
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