The clinical potential of GDF15 as a “ready-to-feed indicator” for critically ill adults

Table 3 Interaction between serum GDF15 concentrations upon ICU admission and randomization to early PN versus late PN for impact on clinical outcome

Outcome
Likelihood of earlier live discharge from ICU	HR (95% CI)	p
1A. GDF15 (per ng/ml added)	0.957 (0.947–0.967)	< 0.0001
1B. Randomization to early PN vs late PN	0.939 (0.883–0.998)	0.04
2. GDF15, randomization and interaction
GDF15 (per ng/ml added)		< 0.0001
Randomization to early PN vs late PN		0.02
Interaction GDF15-randomization		0.21
Risk of new infection	OR (95% CI)	p
1A. GDF15 (per ng/ml added)	1.014 (1.007–1.021)	0.0001
1B. Randomization to early PN vs late PN	1.245 (1.071–1.447)	0.004
2. GDF15, randomization and interaction
GDF15 (per ng/ml added)		< 0.0001
Randomization to early PN vs late PN		0.003
Interaction GDF15-randomization		0.46
Risk of ICU acquired weakness	OR (95% CI)	p
1A. GDF15 (per ng/ml added)	1.026 (1.006–1.045)	0.006
1B. Randomization to early PN vs late PN	1.457 (1.001–2.122)	0.04
2. GDF15, randomization and interaction
GDF15 (per ng/ml added)		0.002
Randomization to early PN vs late PN		0.03
Interaction GDF15-randomization		0.19

Stepwise multivariable models were built including all patients with upon ICU admission serum sample available for GDF15 measurement (N = 4393). Step 1: Models investigating the independent effect of GDF15 concentrations upon ICU admission (step 1A) and randomization to early PN vs late PN (step 1B) on outcome. All models were adjusted for the baseline risk factors age, body mass index, severity of illness, diagnostic category (cardiac surgery, emergency surgical, elective surgical and medical ICU admission), and risk of malnutrition. Step 2: Both GDF15 concentrations upon ICU admission and randomization to early PN versus late PN, as well as the interaction between randomization and GDF15 were included in the model, adjusting for the same baseline risk factors. This allowed to investigate whether upon-admission GDF15 was determining benefit or harm from early PN versus late PN
Abbreviations: ICU intensive care unit, OR odds ratio, CI confidence interval, GDF15 growth-differentiation factor-15, PN parenteral nutrition, HR hazard ratio

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