GDF15 is a stress response cytokine that is induced by injury and inflammation (Tsai et al 2018, Luan et al 2019). Increased levels of GDF15 have been observed in critically ill patients, anorexia nervosa, cancer cachexia and obesity (Clark et al 2013, Buendgens et al 2017, Mullican 2018). It has been suggested that GDF15 may be a driver of critical illness-induced anorexia and GI intolerance (Peterson et al 2010, Heyland et al 1995).
Feasibility/Equipment: Serum GDF15 can be monitored via a blood sample.
Scoring information: Numerous physiological and pathophysiological processes (including heart disease, stroke, cancer, diabetes, body mass index, pregnancy and smoking) can increase circulating GDF15 levels. Potential confounding risk factors should be identified and considered when interpreting GDF15 concentrations (Welsh et al 2022).
Evidence: GDF15 has been proposed as a driver for critical illness-induced anorexia and GI intolerance (Peterson et al 2010, Heyland et al 1995). A study of 1383 mixed ICU patients found serum GDF15 levels on ICU day 4 to be inversely but weakly associated with tolerance of enteral nutrition in the following 24h (OR for risk of intolerance per ng/ml GDF15 increase: 1.027 [1.012; 1.042], p < 0.0001, R2 = 0.008), with limited sensitivity and specificity (area under receiver operating curve (AUROC) 0.57). These associations were independent of baseline risk factor (Van Dyck et al).
Accuracy / measurement properties: A study of 18,507 participants with no heart disease, stroke, previous heart failure hospitalisation, and not known to be pregnant, showed the median overall GDF-15 was 808 pg/mL (IQI 608, 1,103 pg/mL), median GDF-15 in females was 816 (IQI 623–1,103 pg/mL), and median GDF-15 in males was 793 (IQI 588–1,108 pg/mL). In males, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135) pg/mL, rising to 931 (2,492) pg/mL at 50–59 years, and 2,152 (5,972) pg/mL at ≥80 years. In females, median GDF-15 at age <30 years was 628 (2,195) pg/mL, 881 (2,323) pg/mL at 50–59 years, and 1,847 (6,830) pg/mL at ≥80 years. In females in the <30 years and 30–39 year age group there were some outliers that drove up the 99th centile (12,745 pg/mL) much higher than the 99th centile in males (1,820 pg/mL) (Welsh et al 2022). Physiological and pathophysiological processes known to increase GDF15 levels must be considered when interpretting results.