Surgery-specific patterns of perioperative amino acid administration and associated acute kidney injury risk: a large-scale retrospective cohort study

Abstract

Background: Recent trials demonstrated renoprotective effects of amino acid infusion in cardiac surgery patients, but real-world utilization patterns and outcomes across surgical specialties remain unknown. We investigated perioperative amino acid administration patterns and associated acute kidney injury (AKI) risk across different surgical populations.

Methods: Retrospective cohort study using the INSPIRE database (2011-2020) from Seoul National University Hospital. Adult patients undergoing surgery with ≥ 24-h stays were included. Amino acid preparations were identified by ATC codes, and AKI was defined by KDIGO criteria. Primary outcomes were AKI incidence and utilization patterns across surgical departments.

Results: Among 22,972 patients, 899 (3.9%) received peri-operative amino acid preparations with an overall AKI incidence of 3.7%. Utilization varied 60-fold across departments (0.2-11.5%). Surgery-specific patterns emerged: cardiac surgery showed no AKI events in amino acid users (0/50) versus 4.2% in non-users (p = 0.267), while non-cardiac surgery demonstrated increased AKI risk with amino acid use (7.4% vs 3.4%; RR = 2.16, 95% CI 1.65-2.85, p < 0.001). Multivariable analysis confirmed amino acid use as an independent AKI predictor (OR = 2.01, 95% CI 1.52-2.60). Machine learning analysis confirmed amino acids as the strongest AKI predictor, with Random Forest achieving superior performance (AUC-ROC 0.782) and revealing significant non-linear interactions. Propensity score matching (799 pairs) confirmed the association (OR = 1.63, 95% CI 1.05-2.52, p = 0.029).

Conclusions: Perioperative amino acid administration demonstrates surgery-specific patterns with differential AKI associations. These findings suggest that surgery-specific factors should be considered when developing amino-acid protocols, although causality cannot be established from this observational study.

Keywords: Acute kidney injury; Amino acids; Perioperative care; Practice variation; Surgery-specific.

Fig. 1

Perioperative amino acid utilization patterns by department. Stacked bar chart displaying perioperative amino acid utilization rates across eight surgical departments, demonstrating remarkable variation in practice patterns. Utilization rates range from 0.2% in obstetrics/gynecology (OB/GYN) to 11.5% in urology, representing approximately a 60-fold difference in usage patterns. Each bar shows the total utilization rate with a breakdown by preparation type: amino acids (B05BA01, orange), fat emulsions (B05BA02, blue), and parenteral nutrition (B05BA10, green). The highest utilization rates were observed in urology (11.5%), followed by oncology (4%), cardiothoracic surgery (1.9% with additional 1.3% for different preparations), general surgery (1.3%), neurosurgery (1%), orthopedics (0.6%), plastic surgery (0.4%), and obstetrics/gynecology (0.2%). Parenteral nutrition solutions (green) comprised the majority of amino acid preparations across most departments. This substantial variation likely reflects differences in patient complexity, procedure duration, departmental nutritional support protocols, and practice culture, highlighting significant opportunities for evidence-based standardization

Fig. 2

Surgery-specific patterns of amino acid use and AKI risk. Bar chart comparing acute kidney injury (AKI) incidence between amino acid users and non-users, stratified by surgical type (cardiac vs non-cardiac surgery). The chart demonstrates contrasting patterns with error bars representing 95% confidence intervals. In cardiac surgery (green bars), amino acid non-users had 4.2% AKI rate (103/2478 patients) while amino acid users had 0% AKI rate (0/50 patients, p = 0.267), suggesting a protective trend despite not reaching statistical significance. In non-cardiac surgery (red bars), the pattern reverses: non-users had 3.4% AKI rate (674/19,595 patients) while users had significantly higher AKI rates at 7.4% (63/849 patients), yielding a risk ratio of 2.16 (p < 0.001). This differential association across surgical contexts illustrates surgery-specific effects and highlights the critical importance of surgical context in amino acid administration decisions and AKI risk assessment

Fig. 3

Multivariable analysis of risk factors for postoperative AKI. Forest plot displaying adjusted odds ratios (OR) and 95% confidence intervals from multivariable logistic regression analysis predicting postoperative acute kidney injury. The vertical dashed red line at OR = 1.0 represents no association. Variables are ordered by statistical significance and effect magnitude. Amino acid use shows the strongest association with increased AKI risk (OR = 2.01, 95% CI 1.52–2.6, p < 0.001), followed by male sex (OR = 1.58, 95% CI 1.37–1.83, p < 0.001), baseline creatinine (OR = 1.35, 95% CI 1.15–1.58, p < 0.001), and age per year (OR = 1.02, 95% CI 1.01–1.03, p < 0.001). Surgery duration per hour showed no significant association (OR = 1.01, 95% CI 0.97–1.05, p = 0.545). The analysis demonstrates that amino acid administration remains the strongest independent predictor of AKI risk after adjustment for demographic, clinical, and procedural factors

Fig. 4

Machine Learning Model Performance Comparison

Fig. 5

Clinical Risk Stratification Framework Based on Surgery Type and Amino Acid Use