Nephroprotective potential of perioperative intravenous amino acid infusion in cardiac surgery with cardiopulmonary bypass

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BACKGROUND

Cardiac surgery-associated acute kidney injury (AKI) is one of the most common and dangerous complications in patients after cardiac surgery. According to recent international publications, its incidence ranges between 8.9% and 50%, depending on the population and diagnostic criteria [1–3]. Notably, even moderate postoperative AKI is associated with a higher risk of chronic kidney disease (CKD), the need for long-term hemodialysis, and increased long-term mortality rates [4]. Severe AKI requiring renal replacement therapy is reported in 2%–5% of patients but may reach 15%–30% in patients with CKD [2, 3]. In-hospital mortality in dialysis-dependent AKI reaches 40%–60%, and even a minor postoperative creatinine elevation increases the risk of death by 2–3 times [4].

According to retrospective studies, AKI secondary to CKD is associated with a 3–8-fold increase in in-hospital mortality compared to individuals without kidney injury [5]. Moreover, it is associated with more frequent episodes of persistent renal dysfunction, higher readmission rates, and longer ICU stays. Approximately 20%–25% of patients with a history of AKI experience accelerated CKD progression (up to end-stage renal disease), necessitating long-term dialysis.

Cardiac surgery-associated AKI has a complex, multifaceted pathophysiology, which includes ischemia-reperfusion injury, inflammation, oxidative stress, hemolysis, microthrombosis, and hemodynamic compromise [5, 6]. Despite substantial research into pharmacological [6–8] and non-pharmacological [9] nephroprotective strategies, there is no universally effective preventive approach, and clinical findings are frequently conflicting [6, 10].

Early diagnosis and prevention of AKI are becoming increasingly relevant as the most effective strategy to reduce morbidity and mortality rates [6–8]. Management algorithms for these patients and a multidisciplinary approach in real-world clinical practice have demonstrated promising results; however, the need for new solutions remains [9, 10].

One promising preventive strategy is activating renal functional reserve, which is the ability of the kidneys to increase glomerular filtration rate (GFR) in response to metabolic stimulation, such as amino acid administration [11]. Renal functional reserve is activated through vasodilation of afferent arterioles, stimulation of nitrogen oxide production, activation of the renin–angiotensin–aldosterone system, secretion of insulin, glucagon, and prostaglandins, and inhibition of tubuloglomerular feedback [12, 13]. In patients with intact renal function, activating renal functional reserve may improve renal perfusion and reduce the risk of AKI [11, 14]. However, in CKD, these compensatory mechanisms may be compromised, decreasing the kidneys’ adaptive capacity under surgical stress [15, 16].

Therefore, cardiac surgery-associated AKI remains a major concern. Improved prevention strategies may considerably reduce mortality rates and improve the long-term prognosis in these difficult-to-treat patients.

The aim — to assess the nephroprotective potential of continuous perioperative intravenous infusion of a balanced amino acid solution in patients after cardiac surgery with cardiopulmonary bypass.

METHODS

Study Design

This was a randomized, double-blind, placebo-controlled, single-center study with pooled post hoc analysis.

Study Setting

The study was conducted at the Anesthesiology and Intensive Care Unit and the Cardiac Surgery Unit of Sechenov University’s Clinical Hospital No. 1 from January 26, 2021, to December 21, 2024.

The study was initially designed as a parallel analysis in two independent cohorts of patients with and without CKD. In accordance with the approved protocol, the primary endpoint in each cohort was glomerular filtration rate as an integral renal function parameter.

Secondary endpoints in each cohort originally included binary variables such as the incidence of AKI and major adverse kidney events within 30 days (MAKE30). However, after enrollment and data analysis, it was found that the incidence of AKI was lower than predicted. As a result, the study did not have the power to identify significant differences in each cohort. Therefore, post hoc analysis in a pooled sample was performed.

Eligibility Criteria

Inclusion criteria: patients aged 18–75 years; cardiac surgery with cardiopulmonary bypass; ICU stay of more than 12 h; informed consent.

Non-inclusion criteria: participation in another randomized study; decompensated diabetes mellitus, severe hepatic insufficiency (Child–Pugh >7), or acute cardiovascular insufficiency; pregnancy and breastfeeding; intraoperative shock of any origin; history of hypersensitivity to amino acid solutions.

Exclusion criteria: withdrawal of consent; newly diagnosed hypersensitivity, including allergic reactions to amino acid solutions; need for venoarterial extracorporeal membrane oxygenation; decompensated metabolic acidosis.

Study groups. This clinical study enrolled 260 patients who underwent elective cardiac surgery with cardiopulmonary bypass for the first time. Patients were randomized independently within each cohort, stratified by the presence or absence of CKD. Patients were initially randomized into four groups using sealed opaque envelopes, which were prepared prior to enrollment. Study samples were calculated using a formula for comparing two independent means, adjusted for non-normal distribution and missing data [17]. The number of envelopes matched the calculated sample sizes: 128 for the group with intact renal function and 132 for the group with CKD. Each envelope assigned a patient to either the treatment or control group. In the morning on the day of surgery, an anesthesiologist opened a random envelope; the group assignment was not disclosed to maintain the double-blind design. After enrollment and primary data analysis in cohorts, pooled post hoc analysis was performed.

Intervention

Group 1 (n = 130; treatment group) received an infusion of Aminoven 10% (Fresenius Kabi Austria GmbH, Austria) at a dose of 2 g/kg/day (20 mL/kg ideal body weight per day). The infusion started immediately after the induction of anesthesia and lasted for the first 24 h after surgery.

Group 2 (n = 130; control group) received a balanced crystalloid solution (Sterofundin; B. Braun Melsungen AG, Germany) in an equal amount and with the same duration of infusion.

AKI and CKD were confirmed using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria [18, 19]; GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula [20]. All procedures complied with the Consolidated Standards of Reporting Trials (CONSORT) [21].

Anesthesia, cardiopulmonary bypass, and intensive care. Following radial artery catheterization, invasive hemodynamic monitoring, and preoxygenation with 80% oxygen using a face mask, anesthesia was induced using fentanyl 0.2 mg, ketamine 50 mg, midazolam 10 mg, propofol 1–2 mg/kg, and rocuronium bromide 0.6 mg/kg. The anesthesia was maintained using sevoflurane 0.8–1.5 MAC (minimum alveolar concentration). During cardiopulmonary bypass, rocuronium bromide (0.15 mg/kg), fentanyl (0.1–0.2 mg every 40–60 min), and propofol (3–5 mg/kg/h) were used. Protective pressure control ventilation (PCV) was performed in all patients using Dräger Atlan A350 (Drägerwerk AG & Co. KGaA, Germany), with the following parameters: fraction of inspired oxygen (FiO₂) 40%–50%; tidal volume 6–8 mL per 1 kg ideal body weight; positive end-expiratory pressure (PEEP) 5–8 cmH₂O; respiratory rate 10–14 bpm to achieve hemoglobin oxygen saturation (SpO₂) ≥95% and normocapnia. In patients with severe blood loss, autologous blood reinfusion was performed using XTRA (Sorin Group, LivaNova, Italy). The extent of transfusion and hemostatic therapy was determined using rotational thromboelastometry (ROTEM Delta, Tem Innovations GmbH, Germany).

Cardiopulmonary bypass was performed using Stockert S3 and Stockert S5 (Sorin Group, LivaNova, Italy) with an integrated real-time gas analyzer CDI500 (Terumo, USA) and an oxygenator Affinity NT (Medtronic, USA). An ascending aorta-to-right atrium bypass was used. When cannulation of the ascending aorta was not possible, alternative central line insertion techniques were used. Cold blood cardioplegia with Custodiol solution or Calafiore/del Nido cardioplegia was used for circulatory arrest and myocardial protection. The volumetric perfusion rate was selected based on the body surface area. Normothermic or spontaneous hypothermic perfusion was performed.

After surgery, patients were transferred to the ICU for intensive care, vital signs monitoring, and laboratory control. Infusion therapy was used to maintain adequate perfusion and normovolemia. Where necessary, vasopressors and cardiotonic agents were used. After achieving adequate hemodynamics and regaining consciousness and effective spontaneous breathing, mechanical ventilation was discontinued and extubation was performed. In patients with severe blood loss, transfusion therapy and autologous blood reinfusion were performed using XTRA (Sorin Group, LivaNova, Italy). Electrolyte and acid-base disorders were managed, and normoglycemia was maintained. Renal replacement therapy was performed using Prismaflex (Baxter International Inc., Sweden), set ST 150 (Baxter International Inc., Sweden), in the continuous venovenous hemodiafiltration (CVVHDF) mode with predilution and anticoagulation with unfractionated heparin.

Study Outcomes

Main study outcome: the effect of amino acid infusion on GFR as measured using the CKD-EPI formula.

Additional study outcomes: the severity and duration of an AKI episode; MAKE30; renal function parameters (changes in GFR, urine output, diuretic use, need for renal replacement therapy, BUN/Cr in the blood chemistry); length of ICU stay; length of hospital stay.

Outcomes registration. The KDIGO criteria were used for the diagnosis and staging of AKI, based on changes in serum creatinine levels and urine output. The severity of AKI was assessed using the KDIGO stages (1–3), and the duration of AKI was determined as the number of days from the diagnosis to renal function recovery or discharge. Renal function was assessed based on glomerular filtration rate, which was calculated using the CKD-EPI formula according to perioperative and early postoperative changes in serum creatinine levels. Urine output (mL/day) was recorded daily based on ICU monitoring and medical records. Diuretic use was reported as a binary variable (yes/no). MAKE30 is a composite endpoint that includes death, need for renal replacement therapy, or a GFR reduction of ≥25% from baseline within 30 days after surgery. A patient was registered once in the presence of any of these events. BUN/Cr was calculated as a ratio of blood urea nitrogen (BUN) to serum creatinine (Cr), which were determined using conventional blood chemistry at each postoperative time point. The resulting value was used to assess the severity of azotemia and the type of renal dysfunction. The need for renal replacement therapy was assessed based on clinical indications using local intensive care protocols; the actual performance and duration of renal replacement therapy were additionally recorded. The length of ICU stay and total length of hospital stay were calculated in days using data from the hospital’s medical information system. Data were collected prospectively during inpatient treatment and then verified using source medical records to ensure comprehensive, comparable assessments of all secondary outcomes.

Statistical Analysis

Statistical analysis methods. The database was created using Microsoft Excel and Yandex Tables. Statistical analysis was performed in Python 3.12 using the following libraries: pandas, numpy, statsmodels, and scikit-learn. The Shapiro–Wilk test was used for normality testing. The significance level for statistical hypothesis testing was set as 0.05. The following parameters were used to report study outcomes: median (Ме), interquartile range (Q1; Q3), 95% confidence interval (95% CI), mean (M), and standard deviation (SD). The Levene test was used for variance homogeneity testing. The paired Wilcoxon test was used to assess the significance of intragroup differences before and after treatment. The Mann–Whitney U test was used to assess the significance of intergroup differences for non-normally distributed variables. The chi-squared test or z-test was used for categorical variables. The Fisher exact test was used for intergroup comparisons of complication rates. The z-test was used when the Fisher exact test could not be applied (e.g., due to a small sample size). Generalized estimating equations (GEE) were used to assess perioperative changes in GFR. The family-wise error rate (FWER) was assessed by taking into account all associated outcomes (incidence of AKI, cases of severe AKI, duration of AKI, GFR, and MAKE30). At α = 0.05 and five comparisons, the FWER was approximately 22.6% (1–0.95⁵) without corrections. The Holm–Bonferroni correction, which controls the FWER at ≤5% to verify the results, was used to reduce this risk.

RESULTS

Study Sample

The detailed patient randomization and distribution chart is shown in Fig. 1.

 

Fig. 1. Randomization.

 

Sample Characteristics

There were no intergroup differences in the key demographic characteristics, comorbidities, preoperative renal function, and extent of surgery (Tables 1, 2).

 

Table 1

Preoperative characteristics of patients in the study groups

Surgery	Group		P-value
	Amino acid infusion	Control
Mean age, years, Me [IQR]	59 [46; 66]	59 [46; 65]	0.746
Male, n (%)	87 (66.9)	82 (63.1)	0.603
Body mass index, М ± SD	26.6±3.9	27±4.4	0.483
Diabetes mellitus, n (%)	19 (14.6)	20 (15.4)	0.862
Hypertension, n (%)	88 (67.7)	94 (72.3)	0.417
Atrial fibrillation, n (%)	23 (17.7)	20 (15.4)	0.738
Ejection fraction, %, Me [IQR]	58 [52; 63]	58.5 [52; 63]	0.976
Chronic heart failure (NYHA), n (%)	94 (72.3)	93 (71.5)	0.890
Pulmonary hypertension, n (%)	91 (70)	86 (66.2)	0.506
Preoperative renal function
Glomerular filtration rate, mL/min/1.73 m2, М ± SD	74.6±16.7	76.2±17.9	0.528
Creatinine, µmol/L, Me [IQR]	89.5 [80.2; 101.8]	92 [80; 102]	0.850
Creatinine clearance, mL/min/1.73 m2, Me [IQR]	81 [66; 96.8]	83.5 [67; 97.5]	0.440
Urea, mmol/L, Me [IQR]	5.7 [4.8; 7]	5.8 [4.9; 7.1]	0.646
Urine output, mL/day, Me [IQR]	1960 [1700; 2200]	1900 [1700; 2100]	0.595
Furosemide use, n (%)	16 (12.3)	14 (10.8)	0.698
Verospiron use, n (%)	32 (24.6)	30 (23.1)	0.771
Torasemide use, n (%)	15 (11.5)	19 (14.6)	0.462
Chronic kidney disease stage, n (%)
I	5 (3.8)	6 (4.6)	0.758
II	34 (26.2)	35 (26.9)	0.888
IIIA	21 (20.8)	21 (19.2)	0.756
IIIB	6 (4.6%)	4 (3.1)	0.519

Note. NYHA, New York Heart Association.

 

Table 2

Surgery in the study groups

Outcomes	Group, n (%)		P-value
	Amino acid infusion	Control
Coronary artery bypass, mammary coronary bypass:	30 (23,08)	32 (24,62)	0,884
one cardiac valve	48 (36,92)	52 (40)	0,702
two or more cardiac valves	10 (7,69)	9 (6,92)	0,812
ascending aorta	33 (25,38)	28 (21,54)	0,464
other	9 (6,92)	9 (6,92)	1

 

In some recent studies, intraoperative and early postoperative parameters such as the duration of surgery, blood loss, transfusion volume, lactate level, duration of mechanical ventilation, vasopressor use, and inotropic support are viewed as relevant predictors of AKI in patients undergoing cardiac surgery [22, 23]. There were no significant intergroup differences in the intraoperative and early postoperative periods (Supplement 1).

Primary Results

The incidence of AKI in the treatment group was 18.5% vs 29.2% in the control group (odds ratio [OR] 0.55; 95% CI 0.31–0.98; p = 0.042). Moreover, the median duration of AKI was significantly lower in the treatment group than in the control group: 3 [3; 4] days vs 5 [4; 6] days (p = 0.0006). The incidence of severe AKI (stages II and III) was also significantly lower in the treatment group than in the control group: 6.2% vs 17.7% (p = 0.0041).

An analysis of the overall incidence of adverse kidney events (MAKE30) revealed significant intergroup differences. MAKE30 was reported in 13.5% of cases (17/126) in the treatment group vs 24.4% of cases (31/123) in the control group (OR 0.48; 95% CI 0.25–0.90; p = 0.023).

An assessment of renal function parameters revealed that the treatment group had a more favorable postoperative status (day 0 — day of discharge) than the control group. GFR in the treatment group was 79 [61; 93] mL/min/1.73 m², which was significantly higher than in the control group (72 [55; 86] mL/min/ 1.73 m²; p < 0.00001). Serum creatinine levels were also lower in the treatment group than in the control group: 87 [75; 104] µmol/L vs 95 [80; 111.5] µmol/L (p < 0.00001). Creatinine clearance was 83 [65; 103] mL/min in the treatment group vs 80 [63; 96.5] mL/min in the control group (p = 0.0006), confirming the positive effect of amino acid infusion on renal function (Fig. 2).

 

Fig. 2. Perioperative renal function (Me, [IQR]) in the study groups: changes in glomerular filtration rate (a); changes in creatinine clearance (b).

 

Secondary Results

Perioperative changes in GFR were assessed using a generalized estimating equations model. The model demonstrated a significant group × time interaction (Wald χ²(5) = 55.12; p = 1.23 × 10^–¹⁰), indicating intergroup differences in changes in GFR. The baseline (preoperative) GFR values were comparable between the groups (p = 0.468). However, the treatment group had a higher GFR in the early postoperative period: day 0 (Δ + 11.0 mL/min/1.73 m²; p = 0.000073), day 1 (Δ + 10.8 mL/min/1.73 m²; p = 0.000383), day 2 (Δ + 10.0 mL/min/1.73 m²; p = 0.00131). By day 7 and discharge, intergroup differences became insignificant (p = 0.781 and p = 0.427, respectively).

In the early postoperative period, the treatment group had higher GFR values than the control group, indicating the favorable effect of the study treatment. However, this effect was temporary; by day 7 and discharge, there were no significant intergroup differences, indicating that the effect gradually decreased over time (the GEE analysis of changes in GFК is presented in Supplement. 2).

The level of urea, one of the primary protein catabolism and renal function biomarkers in the postoperative period (day 0—day of discharge), was lower in the treatment group (7.19 [5.78; 9.31] mmol/L) than in the control group (7.9 [6.2; 10.29] mmol/L; p = 0.0002), confirming that this nephroprotective strategy is metabolically safe. An analysis of the blood urea nitrogen-to-creatinine ratio (BUN/Cr) in the early postoperative period revealed minimal, transient intergroup differences. On the day of surgery, the treatment group had a slightly higher median BUN/Cr than the control group: 39.9 [32.7; 47.9] vs 36.1 [31.5; 44.3] (p = 0.028). However, as early as on days 1 and 2 post-surgery, there were no significant intergroup differences: 42.5 [34.5; 52.3] vs 41.5 [34.0; 49.0] on day 1 (p = 0.356); 42.8 [35.8; 52.6] vs 44.2 [35.2; 52.4] on day 2 (p = 0.989), respectively. Urine output in the postoperative period (day 0 — day of discharge) was significantly higher in the treatment group than in the control group: 2100 [1800; 2600] mL/day vs 1900 [1700; 2235] mL/day; p < 0.00001 (Supplement 3).

Both groups used diuretics relatively frequently in the early postoperative period. When assessing changes in furosemide use over time, it was significantly less frequent in the treatment group (Fig. 3).

 

Fig. 3. Perioperative changes in furosemide use in the study groups.

 

The Holm–Bonferroni correction was used to control the risk of type I error in multiple comparisons of associated endpoints (GFR, incidence of AKI, cases of severe AKI, duration of AKI, and MAKE30). Following the correction, the differences in changes in GFR (p_Holm = 0.0005), duration of AKI (p_Holm = 0.0024), incidence of severe AKI (stages II–III) (p_Holm = 0.0123), MAKE30 (p_Holm = 0.046), and overall incidence of AKI (p_Holm = 0.042) remained significant.

The need for renal replacement therapy was 2.3% in the treatment group and 3.8% in the control group, with no significant intergroup differences (p = 0.473). Similarly, there were no significant intergroup differences in the duration of renal replacement therapy.

The 30-day mortality was low and comparable between the groups: 0.8% in the treatment group vs 2.3% in the control group (p = 0.314). Moreover, the length of hospital stay was significantly shorter in the treatment group than in the control group (19.5 [15; 25] days vs 21 [17; 28] days; p = 0.015), as was the length of ICU stay (23 [21; 29.8] h vs 24 [22; 46] h; p = 0.046) (Table 3).

 

Table 3

Clinical and renal outcomes in the study groups

Outcomes	Group, n (%)		P-value
	Amino acid infusion	Control
AKI	24 (18.5)	38 (29.2)	0.042
AKI 1 (KDIGO)	16 (12.3)	15 (11.5)	0.848
AKI 2 (KDIGO)	5 (3.8)	16 (12.3)	0.012
AKI 3 (KDIGO)	3 (2.3)	7 (5.4)	0.197
Duration of AKI, days, Me [IQR]	3 [3; 4]	5 [4; 6]	0.0018
Need for RRT	3 (2.3)	5 (3.8)	0.473
Duration of RRT, h, Me [IQR]	34 [27.5; 41.5]	70 [46; 73]	0.143
30-day mortality	1 (0.8)	3 (2.3)	0.314
Length of hospital stay, days, Me [IQR]	19.5 [15; 25]	21 [17; 28]	0.015
Length of ICU stay, h, Me [IQR]	23 [21; 29.8]	24 [22; 46]	0.046

Note. AKI, acute kidney injury; ICU, intensive care unit; KDIGO, Kidney Disease: Improving Global Outcomes; RRT, renal replacement therapy.

 

DISCUSSION

Summary of Primary Results

The study found that intravenous amino acid infusion at a dose of 2 g/kg/day for the first 24 h after the induction of anesthesia reduces the incidence of AKI in patients undergoing cardiac surgery with cardiopulmonary bypass. Moreover, patients who received amino acids had a considerably lower duration of AKI and incidence of severe AKI.

Interpretation

These findings are consistent with those reported by Kazawa et al. [24] for patients after ascending aortic surgery. In their study, intravenous Amiparen (Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan) at a dose of 20 g three times daily for 3 days decreased the incidence of AKI (30.3% vs 56.2%; p = 0.04) and improved urine output (2420 mL vs 1865 mL; p = 0.049). However, there were no intergroup differences in serum creatinine levels.

PROTECTION, the largest multicenter study [25] that included 3511 patients undergoing elective cardiac surgery, also confirmed the nephroprotective effect of amino acid infusion. This study used Isopuramin 10% (Fresenius Kabi Austria GmbH, Austria) at a dose of ≤100 g/day (2 g/kg ideal body weight) for 24–72 h. There was a decrease in the incidence of AKI (26.9% vs 31.7%; OR 0.85; 95% CI 0.77–0.94; p = 0.002). However, there were no significant intergroup differences in the need for renal replacement therapy or length of hospital stay. Our study also found a decrease in both the incidence and severity of AKI, with no decrease in the need for or duration of renal replacement therapy. Previous studies used amino acid solutions such as Aminoparen and Isopuramin, which are not registered in Russia. Our study used Aminoven 10% with a comparable amino acid composition.

In addition to a decrease in the incidence and severity of AKI, there was a considerable improvement in renal function parameters in patients who received amino acid infusions. Mean GFR values in the treatment group were significantly higher than in the control group (79 [61–93] mL/min/1.73 m² vs 72 [55–86] mL/min/ 1.73 m²; p < 0.00001), indicating renal functional reserve activation and preserved adaptive filtration under surgical stress. Moreover, the treatment group had a better urine output on the first day (p < 0.01), with lower furosemide use (p = 0.004), which may indirectly indicate preserved or improved renal perfusion and tubular function.

Comparable effects were previously reported in a pilot study by Pu et al. [26], where amino acid infusions increased eGFR by 10.8% and daily urine output by 300 mL (p = 0.046) compared to the control group. Kazawa et al. [24] reported an increase in urine output and stable creatinine levels and GFR in the treatment group, despite a high risk of AKI at baseline. A decrease in urea levels in the treatment group in our study indicates improved excretory function of the kidneys and, potentially, more effective disposal of nitrogen metabolism products.

Pooled post hoc analysis was necessary because the incidence of AKI did not provide sufficient power to identify significant differences in each cohort. Moreover, there were no significant differences in the key intraoperative and early postoperative parameters that could have a considerable impact on the risk of AKI, confirming the baseline balance of the samples and reducing the risk of confounding factors.

In contrast to the majority of prior research, our study assessed the effect of amino acid infusion not only on the incidence of AKI but also on renal function parameters, including changes in GFR. A repeated measures analysis of perioperative changes in renal function used generalized estimating equations, making it possible to adjust for within-subject correlation and time. Furthermore, our study was the first to assess the duration and severity of AKI, as well as MAKE30, a composite endpoint that reflects clinically significant adverse kidney events. The latter was only assessed in patients with available 30-day follow-up findings. The findings confirm that renal functional reserve activation can be used in real-world clinical practice, a concept that was previously primarily addressed in experimental studies and reviews. The study included patients with chronic kidney disease and used pooled post hoc analysis to assess the therapeutic effect in the most vulnerable population. The Holm–Bonferroni correction improved the reliability of conclusions in multiple comparisons of associated endpoints.

Study Limitations

One limitation of this study is its single-center design, limiting the external validity of the findings. The study did not provide for long-term follow-up; therefore, it was impossible to assess the effect of amino acid therapy on the long-term risk of CKD or the need for renal replacement therapy. Our study did not calculate creatinine clearance in urine, which could provide a more accurate quantitative assessment of renal functional reserve activation [27]. This limits the assessment of the kidneys’ functional response to amino acid therapy. Moreover, the study did not assess modern kidney injury biomarkers (NGAL, TIMP-2, IGFBP7), whose monitoring, according to some research, allows for a more quick and specific assessment of the presence and severity of kidney injury [22, 28].

CONCLUSION

Perioperative amino acid infusion in patients undergoing cardiac surgery with cardiopulmonary bypass significantly improves renal function parameters and decreases the incidence and severity of acute kidney injury. The findings confirm that amino acid infusion is a safe, clinically effective strategy for early nephroprotection in these patients. Multicenter clinical studies are required to assess long-term outcomes of this nephroprotective approach.

ADDITIONAL INFORMATION

Supplement 1. Preoperative characteristics of patients in the study groups.

doi: 10.17816/clinpract688428-4406512

Supplement 2. Perioperative changes in glomerular filtration rate in the study groups based on the GEE analysis.

doi: 10.17816/clinpract688428-4406513

Supplement 3. Perioperative changes in urine output (M, 95% CI) in the study groups.

doi: 10.17816/clinpract688428-4406514

Author contributions: T.Kh. Kasim, manuscript writing, statistical data analysis, and conducting search and analytical work; A.G. Yavorovskiy, M.A. Vyzhigina, E.Yu. Khalikova, S.G. Zhukova, development of the article concept, editing, and approval of the manuscript; I.A. Mandel, development of the concept and manuscript writing, discussion of the study results; M.E. Politov, statistical data analysis, concept development, manuscript writing, and conducting search and analytical work; P.V. Nogtev, supervision of patient management and discussion of study results; E.A. Laricheva, I.V. Lutsenko, patient treatment; K.M. Dubovitsky, M.A. Mechtaeva, V.F. Petrovskii, conducting search and analytical work. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: The study protocol was approved by the Local Ethics Committee of Sechenov University (Protocol No. 01-21 dated January 22, 2021). All patients provided written informed consent to participate in the study. The database was not registered; however, it is available upon request from the journal editors

Funding sources: The study had no sponsorship.

Disclosure of interests: The authors declare that they have no competing interests.

Statement of originality: This manuscript presents the results of a pooled Post Hoc analysis based on data obtained in previously conducted prospective randomized clinical cohorts at Sechenov University. The work has not been published previously and is not under consideration for publication elsewhere.

Data availability statement: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request and with permission of the institutional ethics committee.

Generative AI: Generative artificial intelligence tools were used solely for graphical visualization and formatting of figures. The manuscript text, data analysis, and interpretation were performed entirely by the authors.

About the authors

Timur Kh Kasim

The First Sechenov Moscow State Medical University

Author for correspondence.
Email: kasim_t_kh@staff.sechenov.ru
ORCID iD: 0000-0002-7483-3211
SPIN-code: 1431-5380
Russian Federation, Moscow

Andrey G. Yavorovskiy

The First Sechenov Moscow State Medical University

Email: yavor@bk.ru
ORCID iD: 0000-0001-5103-0304
SPIN-code: 1343-9793

MD, PhD, Professor

Russian Federation, Moscow

Irina A. Mandel

The First Sechenov Moscow State Medical University; Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies

Email: irina.a.mandel@gmail.com
ORCID iD: 0000-0001-9437-6591
SPIN-code: 7778-2184

MD, PhD, Assistant Professor

Russian Federation, Moscow; Moscow

Mikhail E. Politov

The First Sechenov Moscow State Medical University

Email: politov_m_e@staff.sechenov.ru
ORCID iD: 0000-0003-0623-4927
SPIN-code: 2048-9705

MD, PhD, Assistant Professor

Russian Federation, Moscow

Pavel V. Nogtev

The First Sechenov Moscow State Medical University

Email: p_naii@mail.ru
ORCID iD: 0000-0002-5553-0880
SPIN-code: 2803-6502

MD, PhD, Assistant Professor

Russian Federation, Moscow

Elena Yu. Khalikova

The First Sechenov Moscow State Medical University

Email: khalikova_e_yu@staff.sechenov.ru
ORCID iD: 0000-0001-8661-9418
SPIN-code: 5037-0314

MD, PhD, Assistant Professor

Russian Federation, Moscow

Svetlana G. Zhukova

The First Sechenov Moscow State Medical University

Email: zhukova_s_g@staff.sechenov.ru
ORCID iD: 0000-0001-5468-3183
SPIN-code: 9534-2844

MD, PhD, Assistant Professor

Russian Federation

Margarita A. Vyzhigina

The First Sechenov Moscow State Medical University

Email: scorpi1999@mail.ru
ORCID iD: 0000-0002-6024-0191
SPIN-code: 6651-8256

MD, PhD, Professor

Russian Federation, Moscow

Elizaveta A. Laricheva

The First Sechenov Moscow State Medical University

Email: laricheva.elz@gmail.com
ORCID iD: 0000-0002-8709-3451
Russian Federation, Moscow

Konstantin M. Dubovitsky

The First Sechenov Moscow State Medical University

Email: konstantindubovitskii@gmail.com
ORCID iD: 0009-0003-2265-8778
Russian Federation, Moscow

Maria A. Mechtaeva

The First Sechenov Moscow State Medical University

Email: mmechtaeva@yandex.ru
ORCID iD: 0009-0007-1930-1304
Russian Federation, Moscow

Ilya V. Lutsenko

The First Sechenov Moscow State Medical University

Email: Lutsenkobgd231@gmail.com
ORCID iD: 0000-0003-3222-6963
SPIN-code: 7343-0801
Russian Federation, Moscow

Vladimir F. Petrovskii

The First Sechenov Moscow State Medical University

Email: petrovskyvolodymyr@yandex.ru
ORCID iD: 0009-0006-1561-1033
SPIN-code: 4302-3399
Russian Federation, Moscow

References

Supplementary files