The effect of augmented protein intake on nitrogen balance: A nested cohort study of the TARGET protein trial

doi:10.1016/j.jcrc.2026.155706

Organ support & nutrition

The effect of augmented protein intake on nitrogen balance: A nested cohort study of the TARGET protein trial

J Crit CarePublished 27 Aug 2026Nested cohort study within the TARGET Protein cluster randomised crossover trial

Primary result · Nitrogen balanceResultMean difference +5 g per day 95% CI 0.4–10

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Authors' conclusion

In critically ill patients, augmented protein delivery resulted in a less negative nitrogen balance but substantially increased urea generation and plasma urea concentrations.

Study context

Population: Consecutive critically ill patients
Participants: 52 vs 55

Comparison: Augmented vs usual enteral protein intake
Usual proteinn = 52reference
Augmented proteinn = 55
Primary endpoint: Nitrogen balance

Methodological detailssingle-centre

Single-centre

Primary result

As reported in the abstract

Mean difference

+5 g per day

95% CI 0.4–10

P = 0.033

Further findings

Protein intake, day 1 to day 7

Usual proteinmean 0.84 g·kg-1·day-1SD 0.73

Augmented proteinmean 1.35 g·kg-1·day-1SD 0.94

Plasma urea concentration

Usual proteinmedian 11 mmol/L

Augmented proteinmedian 14 mmol/L

Outcome	Estimate	P value
Nitrogen intake	mean difference +7 g per day (95% CI 5–10)	P < 0.001
Urea nitrogen accumulation	difference +3 g (95% CI 1.0–6.0)	P = 0.035

Independent predictors of nitrogen balance (multivariable)

Ideal body weight: −0.18 g.kg-1: −0.18 (95% CI −0.35 to −0.01; P = 0.040)
Acute kidney injury (AKI) at ICU admission: +4.7 g: +4.7 (95% CI 0.10 to 9.3; P = 0.046)
Allocation to augmented protein: +5.1 g: +5.1 (95% CI 0.43 to 9.7; P = 0.033)

Urea nitrogen accumulation

≈60% of additional positive nitrogen balance accounted for by urea generation

Urea increase: mediation through incident AKI

Most of the urea increase attributable to a direct effect rather than mediation through incident AKI

Causal mediation analysis

Safety

Outcome	← Lower odds with augmented protein ←→ Higher odds with augmented protein →	OR (95% CI)	P value
Incident AKI (patients without AKI at ICU admission)Independently associated	0.050.21520	4.79 (1.14–26.4)	P = 0.046
	0.050.21520Odds ratio (log scale)

Original publication

The effect of augmented protein intake on nitrogen balance: A nested cohort study of the TARGET protein trial. J Crit Care. Published 27 August 2026. doi:10.1016/j.jcrc.2026.155706

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