Discussion
AKI, KRT.Critically ill, critically ill
SECONDARY, SEVERE MALNUTRITION, CRITICALLY ILL, MALNUTRITION
In this secondary analysis of the largest RCT comparing protein dose in mechanically ventilated critically ill patients, higher protein dose, as compared to usual dose, in patients with AKI was associated with slower TTDA and increased 60-day mortality regardless of the stages of AKI. Interestingly, this harm did not persist in patients who received KRT, albeit the interaction was not statistically significant. High-dose protein was not associated with longer duration or higher incidence of KRT.Critically ill patients who develop AKI are at risk of protein–energy malnutrition, which is a major negative prognostic factor. Severe malnutrition has been documented in up to 40% of critically ill patients, which is associated with a further increase in morbidity and mortality [There are potential explanations for our findings. First, experimental conditions and theoretical considerations differ from real-world clinical scenarios [Second, while the duration of dialysis and incidence of new dialysis were not significantly affected by the administration of higher proteins, KRT may have reduced a negative effect of higher proteins on outcomes in patients with AKI. KRT trigger a loss of amino acids, small proteins/peptides up to 5–22 g/day and other nutritional losses such as trace elements and vitamins [Third, based on expert consensus, current guidelines postulate that protein requirements are significantly increased in critically ill patients, including those with AKI [In hospitalized patients with AKI not receiving KRT, current nutrition guidelines suggest a range of 1.0–2.0 g/kg/BW/d of protein [Our secondary analysis has several strengths. First, we utilized data from the largest (to date) protein dose RCT in critically ill patients. Second, the data included a diverse sample from multiple practice settings worldwide, all of which enhance the generalizability of the received findings. Third, we identified a hypothesis-generating signal to inform practice and future trial design. We acknowledge several limitations of this exploratory secondary analysis. First, the modality of KRT could impact protein requirements, which was not evaluated in this study that included data from a pragmatic design. Second, post-hoc analysis of RCTs needs to be interpreted cautiously and should be considered hypothesis generating, precluding strong clinical recommendation. Third, as AKI was mainly diagnosed from randomization, we are unable to be certain whether the higher protein dose leads to AKI and worsened clinical outcome, or the continuous high protein dose after AKI is developed worsened clinical outcomes, but we note that the rate of AKI was similar in both protein groups so the later explanation seems more plausible. Nevertheless, we must interpret within subgroup treatment effects cautiously for AKI and all subgroups that were defined based on post-randomization data. Finally, there is a risk of type I errors since several subgroups were tested without adjustment for multiplicity, and conversely there is a risk of type II errors since the study may not be adequately powered for the interaction tests used to determine the significance of subgroup effects. Nevertheless, the overall signal of harm in critically ill patients with AKI cannot be ignored and should be considered in nutrition guidelines and future trial designs.