Impact of early parenteral nutrition on metabolism and kidney injury

Abstract

A poor nutritional state and a caloric deficit associate with increased morbidity and mortality, but a recent multicenter, randomized controlled trial found that early parenteral nutrition to supplement insufficient enteral nutrition increases morbidity in the intensive care unit, including prolonging the duration of renal replacement therapy, compared with withholding parenteral nutrition for 1 week. Whether early versus late parenteral nutrition impacts the incidence and recovery of AKI is unknown. Here, we report a prespecified analysis from this trial, the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. The timing of parenteral nutrition did not affect the incidence of AKI, but early initiation seemed to slow renal recovery in patients with stage 2 AKI. Early parenteral nutrition did not affect the time course of creatinine and creatinine clearance but did increase plasma urea, urea/creatinine ratio, and nitrogen excretion beginning on the first day of amino acid infusion. In the group that received late parenteral nutrition, infusing amino acids after the first week also increased ureagenesis. During the first 2 weeks, ureagenesis resulted in net waste of 63% of the extra nitrogen intake from early parenteral nutrition. In conclusion, early parenteral nutrition does not seem to impact AKI incidence, although it may delay recovery in patients with stage 2 AKI. Substantial catabolism of the extra amino acids, which leads to higher levels of plasma urea, might explain the prolonged duration of renal replacement therapy observed with early parenteral nutrition.

Figure 1.

Time profile of renal function and markers of catabolism. Left panel indicates the daily plasma creatinine, creatinine clearance, plasma urea, plasma urea/creatinine ratio, nitrogen loss, and nitrogen balance from day 1 to 14 for the whole study population, respectively (n=4640; n=3628 included in analyses involving urinary measurements). Bar graphs represent means and 95% confidence intervals. P values lower than 0.01 are shown. *0.001≤P<0.01 and ^$P<0.001 between randomization groups. Center and right panels represent the same parameters from day 1 to 7 and day 14, respectively, for a propensity score-matched subset of patients with a minimum ICU stay of 7 and 14 days, respectively (n=1308 [7 days], n=690 [14 days]; n=760 [7 days], n=328 [14 days] included in analyses involving urinary measurements) (Supplemental Material). Line charts show means and 95% confidence intervals. The P value corresponding to repeated-measures ANOVA is shown.