Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial

Pu, Hong; Doig, Gordon S.; Heighes, Philippa T.; Allingstrup, Mikkel; Wang, Andy; Brereton, John; Pollock, Carol; Chesher, Douglas; Bellomo, Rinaldo

doi:10.1016/j.jtcvs.2018.11.097

Cited by 28 publications

(17 citation statements)

References 33 publications

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“…In line with a recent pilot study [ 42 ], our results suggest that a preoperative high-oral protein load may influence renal outcomes post-cardiac surgery, even though it does not reduce the occurrence of perioperative AKI. Consistent with previous publications [ 25 ], our findings emphasize the incorporation of longer follow-up periods to determine the effects of any intervention on renal function beyond a simple reduction in perioperative AKI.…”

Section: Discussionsupporting

confidence: 88%

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study

et al. 2022

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Background Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects. Methods The prospective “Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation” study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations. Results The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI − 1.4, − 1.7] vs. − 3.3 [95% CI − 4.4, − 2.2] ml/min/1.73 m2) and 12 months (− 2.7 [95% CI − 4.2, − 1.2] vs − 10.2 [95% CI − 11.3, − 9.1] ml/min/1.73 m2; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (− 8.0 [95% CI − 14.1, − 1.9] vs. − 18.6 [95% CI − 23.3, − 14.0] ml/min/1.73 m2; p = 0.008). A dose–response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression. Conclusions A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells. Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).

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Section: Discussionsupporting

confidence: 88%

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study

et al. 2022

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“…This strategy, as shown in a previous study on intensive care unit patients, seems to mitigate the negative effects of cardiopulmonary bypass on kidney function. 4,5 Interestingly, the increment of nitrogenous balance derived from amino acid infusion did not result in an incremented need of continuous renal-replacement therapy, as reported by other experiences. 6 The possible efficacy of amino acids in preventing the progression of AKI is not a new finding, as the concept of renal arteriolar vasodilation, induced by amino acid infusion, was proposed 2 decades ago as a possible mechanism to improve renal perfusion.…”

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confidence: 65%

Commentary: Acute kidney injury: The one-million-pieces puzzle

Bacco

Montisci

Miceli

2019

The Journal of Thoracic and Cardiovascular Surgery

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“…One investigated the effect of intravenous amino acids on renal function in critically ill patients, (20) and the other investigated the protective effect of intravenous amino acids on the kidney in patients undergoing cardiac surgery. (42) The AMIGITS trial results demonstrated that amino acid intake levels of 2.0 g/kg daily were safe and that increased urea levels due to increased amino acid intake did not increase the burden on renal function( 43) but improved eGFR. The underlying mechanism may be related to the diuretic effect of amino acids.…”

Section: Discussionmentioning

confidence: 99%

Effect of amino acid supplementation on short-term complications after gastrointestinal tumor surgery: the AMIGITS randomized clinical trial

Wang

Chen

Zhao

et al. 2023

Preprint

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There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment. To investigate the effect of high-dose amino acid supplementation on the incidence of infection within 30 days after major surgery in patients with gastrointestinal tumors. In this randomized clinical trial, we randomly assigned patients with gastrointestinal tumors to receive either AAS or standard care (SC). The primary outcome was the 30-day postoperative incidence of infection; secondary outcomes included amino acid treatment-related adverse events, in-hospital infectious complications, postoperative hospital stay, other complications, and laboratory test results. We included 407 patients in the intention-to-treat analysis for the primary outcome (AAS group, 204; SC group, 203). During the intervention, the actual mean daily energy intake did not differ significantly between the AAS and SC groups (25.53 vs 25.16 kcal/kg daily, P = .493). However, the actual mean daily amino acid intake was significantly higher in the AAS group than in the SC group (1.81 vs. 0.94 g/kg daily, P < .001). The infection incidence within 30 days of surgery was significantly lower in the AAS group than in the SC group (P = .025). The incidence of amino acid treatment-related adverse events and other complications 30 days postoperatively did not significantly differ between the two groups. The infection incidence during hospitalization was significantly lower in the AAS group than in the SC group (P = .033). Compared to the SC group, the AAS group had significantly shorter postoperative hospital stays (P < .001). AAS is associated with a reduced infection incidence within 30 days of major surgery in patients with gastrointestinal tumors and can be a promising strategy. Trial registration: Chictr.org.cn, ChiCTR2200056258.

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Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial

Cited by 28 publications

References 33 publications

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study

Commentary: Acute kidney injury: The one-million-pieces puzzle

Effect of amino acid supplementation on short-term complications after gastrointestinal tumor surgery: the AMIGITS randomized clinical trial

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