Cardiac Surgery-associated Acute Kidney Injury Research Articles

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein 7 (IGFBP7) for the prediction of acute kidney injury following cardiac surgery.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinases-2 • insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2•IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2•IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery. In the prospective cohort study, blood and urine samples were collected 6-12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes. A total of 557 patients were enrolled, 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland clinical score, and simplified renal index than those without AKI. Urinary TIMP-2•IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2•IGFBP7 value of 0.265 (ng/ml)2/1,000. The TIMP-2•IGFBP7 values, simplified renal index (SRI) Score and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint, the percentage of patients who reached the composite end-point in the TIMP-2•IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/ml)2/1,000 group. Postoperative implementation of TIMP-2•IGFBP7 improved prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/ml))2/1,000 for the prediction of CSA-AKI among all AKI patients.

Perioperative Left Ventricular Assist Device Use in Patients With Reduced Ejection Fraction Reduces Cardiac Surgery-Associated Acute Kidney Injury.

Background Cardiac surgery may precipitate acute kidney injury (AKI), particularly in patients with poor baseline cardiac function. This is thought to be due to intraoperative renal hypoperfusion, which results in increased morbidity and mortality. This study evaluated the perioperative use of the Impella LD (Abiomed, Danvers, MA) left ventricular assist device (LVAD) in the prevention of postoperative AKI in patients with reduced left ventricular ejection fraction (LVEF) undergoing cardiac surgery. Methods A retrospective analysis was performed at Northwest Medical Center, Tucson, AZ, USA, on patients undergoing valve surgery, coronary arterybypassgrafting(CABG), or both by a single surgeon. Those with preoperative LVEF ≤35% and preoperative serum creatinine ≥1 mg/dL were included and segregated based on intraoperative LVAD implantation. Postoperative renal functionwas assessed using serum creatinine levels and KDIGO (Kidney Disease Improving Global Outcomes) criteria to define AKI. Results Twenty-three patients were enrolled. There were no significant differences in age, demographics, baseline characteristics, or comorbidities between the treatment (n = 12) and the control group (n = 11). In the treatment group, 8% developed AKI by POD#7, while 64% of controls did. The treatment group had a significantly lower mean creatinine change from POD#0-7 (0.07 vs. 0.59, p = 0.02). However, there was no significant difference between groups in the mean creatinine change from baseline to discharge (0.46 vs. 0.42, p = 0.47). Conclusions Our study suggests that intraoperative Impella implantation may reduce the incidence of early postoperative AKI. LVAD implantation is an approach to increase and ensure adequate end-organ (renal) perfusion andcan improve postoperative recovery without dialysis requirements. Additional studies are required to understand its protective effects during the perioperative period fully.

Amino acids to prevent cardiac surgery-associated acute kidney injury: a randomized controlled trial

BackgroundThis study aimed to examine the preventive effect of amino acids on postoperative acute kidney injury (AKI).MethodsThis was single-center, patient- and assessor-blinded, randomized controlled trial. Patients who underwent aortic surgery with cardiopulmonary bypass were included. The intervention group received 60 g/day of amino acids for up to 3 days. The control group received standard care. The primary outcome was the incidence of AKI. We assessed the effect of amino acids on AKI using a Cox proportional hazards regression model.ResultsSixty-six patients were randomly assigned to the control or intervention group. One patient in the control group withdrew consent after randomization. The incidence of AKI was 10 patients (30.3%) in the intervention group versus 18 patients (56.2%) in the control group (adjusted hazard ratio, 0.44; 95% confidence interval, 0.20–0.95; P = 0.04).ConclusionsThis trial demonstrated a significant reduction in AKI incidence with amino acid supplementation.Trial registrationjRCT, jRCTs051210154. Registered 31 December 2021, https://jrct.niph.go.jp/re/reports/detail/69916

Hemodynamic Determinants of Cardiac Surgery-Associated Acute Kidney Injury.

Examine the: 1) relative role of hemodynamic determinants of acute kidney injury (AKI) obtained in the immediate postcardiac surgery setting compared with established risk factors, 2) their predictive value, and 3) extent mediation via central venous pressure (CVP) and mean arterial pressure (MAP). Retrospective observational study. The main outcome of the study was moderate to severe AKI, per kidney disease: improving global outcomes, within 14 days of surgery. U.S. academic medical center. Adult patients undergoing cardiac surgery between January 2000 and December 2019 (n = 40,426) in a single U.S.-based medical center. Pulmonary artery catheter measurements were performed at a median of 102 minutes (11, 132) following cardiopulmonary bypass discontinuation. None. The median age of the cohort was 67 years (58, 75), and 33% were female; 70% had chronic hypertension, 29% had congestive heart failure, and 3% had chronic kidney disease. In a multivariable model, which included comorbidities and traditional intraoperative risk factors, CVP (p < 0.0001), heart rate (p < 0.0001), cardiac index (p < 0.0001), and MAP (p < 0.0001), were strong predictors of AKI, and superseded factors such as surgery type and cardiopulmonary bypass duration. The cardiac index had a significant interaction with heart rate (p = 0.026); a faster heart rate had a differentiating effect on the relationship of cardiac index with AKI, where a higher heart rate heightened the risk of AKI primarily in patients with low cardiac output. There was also significant interaction observed between CVP and MAP (p = 0.009); where the combination of elevated CVP and low MAP had a synergistic effect on AKI incidence. Hemodynamic factors measured within a few hours of surgery showed a strong association with AKI. Furthermore, determinants of kidney perfusion, namely CVP and arterial pressure are interdependent; as are constituents of stroke volume, that is, cardiac output and heart rate.

Cardiac Surgery-Associated Acute Kidney Injury in Neonates Undergoing the Norwood Operation: Retrospective Analysis of the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network Dataset, 2015-2018.

Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with adverse outcomes. Single-center studies suggest that the prevalence of CS-AKI is high after the Norwood procedure, or stage 1 palliation (S1P), but multicenter data are lacking. A secondary analysis of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) multicenter cohort who underwent S1P. Using neonatal modification of Kidney Disease Improving Global Outcomes (KDIGO) criteria, perioperative associations between CS-AKI with morbidity and mortality were examined. Sensitivity analysis, with the exclusion of prophylactic peritoneal dialysis (PD) patients, was performed. Twenty-two hospitals participating in the Pediatric Cardiac Critical Care Consortium (PC4) and contributing to NEPHRON. Three hundred forty-seven neonates (< 30 d old) with S1P managed between September 2015 and January 2018. None. Of 347 patients, CS-AKI occurred in 231 (67%). The maximum stages were as follows: stage 1, in 141 of 347 (41%); stage 2, in 51 of 347 (15%); and stage 3, in 39 of 347 (11%). Severe CS-AKI (stages 2 and 3) peaked on the first postoperative day. In multivariable analysis, preoperative feeding was associated with lower odds of CS-AKI (odds ratio [OR] 0.48; 95% CI, 0.27-0.86), whereas prophylactic PD was associated with greater odds of severe CS-AKI (OR 3.67 [95% CI, 1.88-7.19]). We failed to identify an association between prophylactic PD and increased creatinine (OR 1.85 [95% CI, 0.82-4.14]) but cannot exclude the possibility of a four-fold increase in odds. Hospital mortality was 5.5% (n = 19). After adjusting for risk covariates and center effect, severe CS-AKI was associated with greater odds of hospital mortality (OR 3.67 [95% CI, 1.11-12.16]). We failed to find associations between severe CS-AKI and respiratory support or length of stay. The sensitivity analysis using PD failed to show associations between severe CS-AKI and outcome. KDIGO-defined CS-AKI occurred frequently and early postoperatively in this 2015-2018 multicenter PC4/NEPHRON cohort of neonates after S1P. We failed to identify associations between resource utilization and CS-AKI, but there was an association between severe CS-AKI and greater odds of mortality in this high-risk cohort. Improving the precision for defining clinically relevant neonatal CS-AKI remains a priority.

Decreased Intraoperative Renal Tissue Oxygenation after Cardiopulmonary Bypass Predicts Cardiac Surgery-Associated Acute Kidney Injury in Neonates.

(1) Background: Near-infrared spectroscopy (NIRS) is a noninvasive tool frequently used during cardiac surgery and postoperatively in the cardiac intensive care unit to monitor regional tissue oxygen saturation. A relationship between trends of intraoperative renal oxygenation and the risk of developing cardiac surgery-associated acute kidney injury (AKI) post-operatively has not yet been established in the neonatal population. The objective of this study is to evaluate the relationship of cerebral and renal oxygenation during cardiopulmonary bypass with cardiac surgery-associated AKI in the first 72 h post-operation in neonates < 30 days of age. (2) Methods: A prospective cohort study at a tertiary care children's hospital was performed. Renal and cerebral oxygenation measured were collected intraoperatively from neonates < 30 days of age who underwent cardiopulmonary bypass for the correction of congenital heart disease. AKI was defined accordance with the Kidney Disease: Improving Global Outcomes criteria modified for neonates. Variables were compared between groups. (3) Results: 32 neonates with 35 cardiopulmonary bypass cases were included. AKI was diagnosed in 60% of cases. Intra-operative renal oxygenation, both on- and off-bypass, did not differ among the three AKI groups (p > 0.19). Renal oxygenation after coming off, but not during, cardiopulmonary bypass steadily decreased with increasing levels of AKI (Jonckheere's test, one-sided p = 0.024). (4) Conclusions: Renal oxygenation decreased in proportion to AKI severity after coming off, but not during, cardiopulmonary bypass.

Protein kinase N1 level predicts acute kidney injury in patients undergoing cardiac surgery：A prospective cohort study.

The objective of this study is to examine the utility of protein kinase N1 (PKN1) as a biomarker of cardiac surgery-associated AKI (CSA-AKI). A prospective cohort study of 110 adults undergoing on-pump cardiac surgery was conducted. The associations between post-operative PKN1 and CSA-AKI, AKI severity, need for renal replacement therapy (RRT), duration of AKI, length of ICU stay and post-operative hospital stay were evaluated. Patients were categorized into three groups according to PKN1 tertiles. The incidence of CSA-AKI in the third tertile was 3.4-fold higher than that in the first. PKN1 was an independent risk factor for CSA-AKI. The discrimination of PKN1 to CSA-AKI assessed by ROC curve indicated that the AUC was 0.70, and the best cutoff was 5.025ng/mL. This group (>5.025ng/mL) was more likely to develop CSA-AKI (P<0.001). The combined AUC of EuroSCORE, aortic cross-clamp time and PKN1 was 0.82 (P<0.001). A higher level of PKN1 related to increased need for RRT, longer duration of AKI, and length of ICU and post-operative hospital stays. PKN1 could be a potential biomarker for the prediction of CSA-AKI. The combination of PKN1, EuroSCORE and aortic cross-clamp time were likely to predict the occurrence of CSA-AKI.

Predictive Values of Hematological Indices in Detecting Cardiac Surgery-Associated Acute Kidney Injury

Predictive Values of Hematological Indices in Detecting Cardiac Surgery-Associated Acute Kidney Injury

Serum CIRP increases the risk of acute kidney injury after cardiac surgery.

Acute kidney injury (AKI) is a frequent perioperative complication. The underlying mechanisms of cardiac surgery-associated AKI are still not completely elucidated. Cold-induced RNA-binding protein (CIRP) has been subsequently found to be regulated by various stress conditions. During cardiac surgery and cardiopulmonary bypass (CPB), the host is subjected to hypothermia and inadequate organ perfusion, resulting in an upregulation of CIRP secretion. The aim of this study is to evaluate the role of elevated extracellular CIRP level as a contributing factor in the development of AKI. A total of 292 patients who underwent cardiac surgery were retrospectively enrolled and their serum samples were collected preoperative and postoperative. Demographic data, intraoperative data, in-hospital outcomes, and the occurrence of AKI were also collected for the patients. The correlation between CIRP and intraoperative procedures, as well as its association with postoperative outcomes were analyzed. In multivariable analysis, higher ΔCIRP (p = 0.036) and body mass index (p = 0.015) were independent risk factors for postoperative AKI. Meanwhile, patients with postoperative AKI exhibited lower survival rate in 2-year follow-up (p = 0.008). Compared to off-pump coronary artery bypass grafting surgery, patients who underwent on-pump coronary artery bypass grafting, valve surgery, aortic dissection and other surgery showed higher ΔCIRP, measuring 1,093, 666, 914 and 258 pg/mL, respectively (p < 0.001). The levels of ΔCIRP were significantly higher in patients who underwent CPB compared to those who did not (793.0 ± 648.7 vs. 149.5 ± 289.1 pg/mL, p < 0.001). Correlation analysis revealed a positive correlation between ΔCIRP levels and the duration of CPB (r = 0.502, p < 0.001). Patients with higher CIRP levels are at greater risk of postoperative AKI (OR: 1.67, p = 0.032), especially the stage 2-3 AKI (OR: 2.11, p = 0.037). CIRP secretion increases with prolonged CPB time after cardiac surgery, and CIRP secretion is positively correlated with the duration of CPB. Cardiac surgeries with CPB exhibited significantly higher levels of CIRP compared to non-CPB surgeries. Elevation of CIRP level is an independent risk factor for the incidence of AKI, especially the severe AKI, and were associated with adverse in-hospital outcomes.

Association between serum homocysteine and postoperative acute kidney injury in patients undergoing cardiac surgery.

Background: To explore the relationship between homocysteine (Hcy) and cardiac surgery-associated acute kidney injury (AKI). Methods: A total of 944 patients who underwent cardiac surgery were enrolled. The association between Hcy levels and the risk of cardiac surgery-associated AKI was evaluated. Results: A total of 135 patients were diagnosed with AKI and the prevalence of AKI was 14.30%. The AKI group had significantly higher levels of Hcy compared with the non-AKI group (16.90 vs 13.56umol/l; p<0.001). The incidence rates of AKI increased from 7.2% to 26.72% across increasing Hcy quartiles (p<0.001). Compared with the firstHcy quartile group, the odds ratio of cardiac surgery-associated AKI was 4.43 (95% CI: 2.27-8.66) in the highest Hcy group. Conclusion: Elevated Hcy level is an independent risk factor for cardiac surgery-associated AKI.

Tissue inhibitor of metalloproteinase-2 in patients aged 1 month to 1 year with and without cardiac surgery-associated acute kidney injury in congenital heart disease surgery with cardiopulmonary bypass: a single-center retrospective study

Introduction: Acute kidney injury is a common complication of cardiac surgery after management of congenital heart defects. Cardiac surgery-associated acute kidney injury (CS-AKI) results in longer stays of patients in the intensive care unit and hospital. However, using an increase in postoperative creatinine as a means of detecting AKI has some limitations, since significant changes occur after the loss of more than 50% of renal function. In children, the creatinine level is influenced by various factors such as muscle mass, cardiac output, etc. These factors vary significantly among young children and complicate the early diagnosis of AKI. Recent studies have explored biomarkers as potential predictors for the early detection of CS-AKI after cardiac surgery for management of congenital heart disease in children.Objective: To evaluate the urinary tissue inhibitor of metalloproteinase-2 (TIMP2) as a predictor of CS-AKI following management of congenital heart defects in children aged 1 month to 1 year who underwent cardiopulmonary bypass.Methods: A single-center retrospective study included patients aged 1 month to 1 year who underwent cardiopulmonary bypass for the correction of congenital heart defects. The groups were formed based on the presence of CS-AKI. The study group comprised of patients who had CS-AKI (group 1, n = 52), while those without CC-AKI constituted the control group (group 2, n = 98). To ensure minimal systematic errors and comparability between two groups, propensity score matching analysis was performed (52 patients in groups 1 and 2). Preoperative, intraoperative, and postoperative parameters and characteristics were compared.Results: The results showed no differences in baseline or demographic characteristics between the patients. In the study group, 34.6% of patients were diagnosed with CS-AKI. Among them, 67.4% (n = 35) were stage 1, 28.8% (n = 15) were stage 2, and 3.8% (n = 2) were stage 3. The results of the regression analysis show a decrease by 24% and an increase by 9 and 16% in CS-AKI respectively, with an increase in creatinine levels by 1 µmol/l, at baseline and on days 3 and 4. Additionally, male patients have a 76% lower likelihood to develop CS-AKI. It was observed that there was no significant difference in the tissue inhibitor of metalloprotease-2 levels between the groups with and without CS-AKI.Conclusion: Urinary TIMP2 levels were found to be unable to predict the early onset of CS-AKI in congenital heart defect patients ages 1 month to 1 year who underwent cardiopulmonary bypass surgery. Received 24 April 2023. Revised 27 November 2023. Accepted 28 November 2023. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authors: The authors contributed equally to this article.

Association of cardiopulmonary bypass with acute kidney injury in patients undergoing coronary artery bypass grafting: a retrospective cohort study.

To the Editor: Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgeries. Cardiopulmonary bypass (CPB)-assisted cardiac surgery was associated with a higher incidence of AKI than other surgeries without CPB, suggesting that CPB might be a risk factor for cardiac surgery-associated AKI (CSA-AKI).[1] However, previous studies have demonstrated conflicting results regarding the association of CPB and CSA-AKI, as the diagnosis of AKI has been made according to different criteria.[2-5] The most recent definition of AKI from an AKI Work Group, Kidney Disease: Improving Global Outcomes (KDIGO), allows for the determination of AKI based on a decline in the glomerular filtration rate (GFR) with subsequent increase in serum creatinine or a period of oliguria.[6] We performed a retrospective cohort study to evaluate the association of CPB and postoperative AKI, using the KDIGO definition among patients undergoing on-pump or off-pump coronary artery bypass graft (CABG). From September 29, 2016, to October 07, 2017, patients aged ≥18 years who underwent elective, isolated CABG at Xijing Hospital were included. The exclusion criteria included a history of previous cardiac surgery, hemodynamic instability, estimated GFR of <30 mL·min−1·1.73 m−2 at baseline, or unavailability of a baseline renal function test. Hemodynamic instability here constitutes preoperative cardiogenic shock and use of preoperative intra-aortic balloon pump (IABP), ventricular assist devices, or preoperative cardiopulmonary resuscitation. Our study adheres to the guidelines for Strengthening the Reporting of Observational Studies in Epidemiology. We collected baseline demographic information and data on clinical comorbidities and preoperative medications from all patients from the cardiothoracic surgery database at Xijing Hospital. Data on intraoperative anesthesia management were obtained from anesthesia and medical records of Xijing Hospital. Age, sex, GFR, ejection fraction (EF), European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), and history of diabetes, hypertension, myocardial infarction (MI), stroke, peripheral arterial disease, and chronic obstructive pulmonary disease were determined from the electronic health records. Preoperative use of the following medications was also recorded: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), diuretics, calcium channel blockers, nitrates, and β-blockers, and whether β-blockers were administered in the morning of the day of the surgery. Serum creatinine level and EF at baseline were defined as the latest measurements before surgery. GFR was estimated using the Cockcroft-Gault equation: GFR=[(140 − age) × (weight in kg) × (0.85 if female)]/(72 × serum creatinine). The following intraoperative variables were collected: duration of the operation, number of grafts, adverse events, sufentanyl dosage, and use of IABPs. The primary outcome was the incidence of postoperative AKI. We adopted the definition of AKI by the KDIGO, as a rise in serum creatinine by 0.3 mg/dL in 48 h or a rise in serum creatinine 1.5 times the baseline over 7 postoperative days.[7] As urine output was unavailable after patients were discharged from the intensive care unit (ICU), it was not used to diagnose AKI in this study. Secondary outcomes were in-hospital medical expenses, length of stay, mortality, and composite outcomes including all-cause mortality, MI, stroke, repeat revascularization, or acute renal failure requiring renal replacement therapy. Composite outcomes were determined 1 year after surgery via a follow-up phone call. Definitions of secondary outcomes and telephone follow-ups are described in the Supplementary Materials, https://links.lww.com/CM9/B348. This study was approved by the Institutional Ethics Review Committee of Xijing Hospital (approval No. KY20192156-C-1). It was exempt from the requirement of informed consent due to ethical considerations, and we obtained the oral consent of patients via telephone follow-up. The patients volunteered to tell their long-term outcomes, to which no patient objected. All tests and confidence intervals (CIs) were two-sided, and statistical significance was set at P < 0.05. All analyses were conducted using R (http://www.R-project.org, c) and Free Statistics software version 1.4 (Beijing FreeClinical Medical Technology Co., LTD, China). Please refer to the supplementary material, https://links.lww.com/CM9/B348 for a detailed statistical analysis. Between September 29, 2016, and October 7, 2017, 242 patients underwent isolated CABG. Eight patients were excluded from the study: two had a history of cardiac surgery, one had an estimated GFR of <30 mL·min−1·1.73 m−2 at baseline, two died prior to the postoperative renal function test, two had duplicated electronic medical records, and one was missing serum creatinine data. In total, 234 patients (195 [83.3%] men and 39 [16.7%] women) were included in the final study analysis; 107 (46%) underwent on-pump CABG and 127 (54%) underwent off-pump CABG [Supplementary Figure 1, https://links.lww.com/CM9/B348]. The mean age of the patients was 61.3 ± 7.6 years. The mean preoperative GFR was 67.0 ± 15.8 mL·min−1·1.73 m−2, the median of EuroSCORE II was 1.2 (interquartile range [IQR]: 0.9–1.7), and the mean preoperative EF was 54.4 ± 7.1. Supplementary Table 1, https://links.lww.com/CM9/B348 shows the main demographic characteristics and incidence of preoperative comorbidities grouped by patients who underwent on-pump or off-pump procedures. Compared with patients who underwent on-pump CABG, more patients in the off-pump group were provided with nitrates and β-blockers preoperatively (66.9% vs. 48.6%, P = 0.007 for nitrates; 92.1% vs. 68.2%, P < 0.001 for β-blockers). Patients in the off-pump group tended to have less vessels grafted, shorter operative duration (142.4 ± 38.0 min vs. 268.1 ± 55.5 min, P < 0.001), less intraoperative sufentanyl administered (250.0 [IQR: 225.0–300.0] μg vs. 450 [IQR: 387.5–500.0] μg, P < 0.001), and higher standardized sufentanyl dose (by operative time and expressed as microgram per minute) (1.8 [IQR: 1.4–2.1] μg/min vs. 1.7 [IQR: 1.4–2.0] μg/min, P = 0.046). During the first 7 postoperative days, 117 AKI events occurred in the entire cohort, including 105 stage I AKIs, 7 stage II AKIs, and 5 stage III AKIs; and one patient required renal replacement therapy. The incidence of postoperative AKI was 69.1% in the on-pump CABG cohort and 33.9% in the off-pump CABG cohort (absolute risk difference, 35.2% [95% CI, 23.3–47.3%]) [Supplementary Table 2, https://links.lww.com/CM9/B348]. The association between CPB exposure and postoperative AKI is shown in Table 1. In the unadjusted model, exposure to CPB was associated with an increased risk of postoperative AKI (risk ratio, 2.04 [95% CI, 1.40–2.97], P<0.001). In the adjusted models, after the potential confounders were adjusted and controlled, the direction of association was unchanged. A potential confounder was statistically significant in the univariate analysis of factors affecting AKI [Supplementary Table 3, https://links.lww.com/CM9/B348]. In the fully adjusted model, in which we adjusted for age, sex, GFR, preoperative use of β-blockers, number of grafts, EuroSCORE II, standardized sufentanyl dose, preoperative use of digoxin, and history of stroke, CPB was an independent risk factor for AKI (relative risk [RR], 1.73, [95% CI, 1.14–2.63], P = 0.01) during the first 7 postoperative days. The association with postoperative AKI was statistically significant in all strata of the population investigated according to age, sex, history of stroke, history of diabetes, history of hypertension, history of MI, preoperative use of ACEI or ARB, and preoperative GFR [Supplementary Figure 2, https://links.lww.com/CM9/B348]. The E-values of the RR for the point estimate and lower confidence bound for the incidence of AKI were 2.85 and 1.54, respectively. Table 1 - Association between CPB and incidence of AKI using poisson regression models. Poisson regresssion models Crude Model 1 Model 2 Model 3 Model 4 Groups RR (95% CI) P value RR (95% CI) P value RR (95% CI) P value RR (95% CI) P value RR (95% CI) P value Off-pump 1.00 NA 1.00 NA 1.00 NA 1.00 NA 1.00 NA On-pump 2.04 (1.40, 2.97) <0.001 1.79 (1.18, 2.71) 0.006 1.77 (1.17, 2.68) 0.007 1.75 (1.15, 2.65) 0.008 1.73 (1.14, 2.63) 0.010 Model 1: adjusted for age, sex, GFR, preoperative use of β-blockers, and number of grafts. Model 2: adjusted for age, sex, GFR, preoperative use of β-blockers, number of grafts, and EuroSCORE II. Model 3: adjusted for age, sex, GFR, preoperative use of β-blockers, number of grafts, EuroSCORE II, and standardized sufentanyl dose. Model 4: adjusted for age, sex, GFR, preoperative use of β-blockers, number of grafts, EuroSCORE II, standardized sufentanyl dose, preoperative use of digoxin, and history of stroke. AKI: Acute kidney injury; CI: Confidence interval; CPB: Cardiopulmonary bypass; EuroSCORE II: European System for Cardiac Operative Risk Evaluation II; GFR: Glomerular filtration rate; NA: Not available; RR: Relative risk. The on-pump CABG group was associated with a significant increase in total costs, postoperative costs, length of ICU stay, and postoperative in-hospital stay compared with the off-pump CABG group [Supplementary Table 2, https://links.lww.com/CM9/B348]. AKI was associated with increased costs and length of hospital stay after adjusting for potential confounders [Supplementary Table 4, https://links.lww.com/CM9/B348]. The CORONARY trial reported a reduction in ICU stay as a secondary outcome in patients undergoing off-pump CABG,[3] which is consistent with our findings. Mediation analysis demonstrated that the increased incidence of AKI mediated a 18.17% increment in postoperative costs, as well as a 17.10% increase in total costs and a 25.69% increase in the length of postoperative in-hospital stay after on-pump CABG [Supplementary Figure 3, https://links.lww.com/CM9/B348]. Follow-up at 1 year was completed in 215 patients (91.5%). All-cause mortality was 5.2% and 4.1% in the off-pump and on-pump groups, respectively (P = 0.73). There was no statistically significant difference in the rate of 1-year composite outcomes between the off-pump and on-pump groups (24.1% vs. 28.6%; P = 0.47) [Supplementary Figures 4, https://links.lww.com/CM9/B348 and 5, https://links.lww.com/CM9/B348]. However, the 1-year all-cause mortality (P = 0.06) and composite outcomes (P = 0.0072) were significantly higher in patients who developed postoperative AKI than in those who did not, regardless of whether the surgery was performed with or without CPB assistance [Supplementary Figures 6, https://links.lww.com/CM9/B348 and 7, https://links.lww.com/CM9/B348]. This single-center observational study was limited by the inherent limitations due to its retrospective nature. We did not collect data on preoperative contrast. However, there was no difference in baseline GFR levels, which may rule out the possibility of contrast-induced kidney damage. In addition, the E-values indicated that the observed RR of 1.73 for incident AKI could only be explained by unmeasured confounders, such as contrast exposure, by a risk ratio of >2.85, and beyond that of the confounders that were measured in this study (lower confidence bound, 1.54). According to the KDIGO definition, the risk of AKI after CABG was significantly higher in the on-pump group than in the off-pump group, with a 73% RR increase for AKI in patients exposed to CPB after adjustment for confounding factors. Meanwhile, our subgroup analysis revealed a consistent and robust association between CPB and the risk of AKI across strata. Additional studies are warranted to replicate and confirm these findings using different surgical procedures and in different populations. If an association or causality is established, this may justify a shift toward less invasive surgical procedures. Furthermore, if CPB is deemed necessary, intensive and comprehensive renal protective strategies should be considered when caring for such patients. Funding This work is supported by a grant from the Natural Science Foundation of China (No. 81970448). Conflicts of interest None.

Improving the performance of the Cleveland Clinic Score for predicting acute kidney injury after cardiac surgery: a prospective multicenter cohort study.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is associated with high short- and long-term mortality rates. The prediction of CSA-AKI is crucial for early detection and treatment. Current predictive models may be improved by potentially useful preoperative and intraoperative information. This multicenter prospective cohort study recruited 261 consecutive patients at high risk for developing CSA-AKI, based on a Cleveland Clinical Score (CCS) of ≥4 points from July to December 2017 in 14 hospitals in Spain and the UK. Postoperative AKI occurred in 145 (55.5%) patients. The receiver operating characteristics curve (AUC) of a base model including only the CCS was compared with models including additional preoperative and intraoperative variables such as the estimated glomerular filtration rate (eGFR) instead of plasmatic creatinine, intraoperative urine output, baseline hemoglobin, nadir hemoglobin, and glycosylated hemoglobin (HbA<inf>1c</inf>) instead of diabetes mellitus. The performance of each model for AKI was compared. The CCS alone gave an AUC of 0.67 (95% CI, 0.56-0.78) for postoperative AKI. None of the single variables added to the base model CCS improve discrimination. The AUC for postoperative AKI was improved when baseline hemoglobin, eGFR instead of plasmatic creatinine, HbA<inf>1c</inf>, and nadir hemoglobin were added to the CCS (AUC=0.77; 95% CI, 0.67-0.87; P=0.02). The addition of baseline hemoglobin, eGFR, HbA<inf>1c</inf>, and nadir intraoperative hemoglobin may be useful for improving the discrimination of the clinical predictive risk scores for AKI.

Association Between Loop Diuretics and Mortality in Patients With Cardiac Surgery-Associated Acute Kidney Injury: A Retrospective Propensity Score-Weighted Analysis.

Although loop diuretics (LDs) have been widely used in clinical practice, their effect on mortality when administered to patients experiencing cardiac surgery-associated acute kidney injury (CS-AKI) remains unknown. The study aimed to investigate the effectiveness of LD use in patients with CS-AKI. Patients who underwent cardiac surgery with AKI were identified from the Medical Information Mart for Intensive Care III. Postoperative LD use in intensive care units (ICUs) was exposure. There were 2 primary outcome measures, the in-hospital mortality and ICU mortality; both were treated as time-to-event data and were analyzed via multivariable Cox proportional hazard models. Inverse probability weighting (IPW) was used to minimize bias. The study enrolled a total of 5478 patients, with a median age of 67 years, among which 2205 (40.3%) were women. The crude in-hospital and ICU mortality rates were significantly lower in the LD use group (525 of 4150 [12.7%] vs 434 of 1328 [32.7%], P < .001; 402 of 4150 [9.69%] vs 333 of 1328 [25.1%], P < .001). Adjusted hazard ratios suggested significant reductions in both in-hospital (hazard ratio [HR], 0.428; 95% confidence interval [CI], 0.374-0.489) and ICU mortality (HR, 0.278; 95% CI, 0.238-0.327). The IPW data showed a similar reduction, in-hospital mortality (HR, 0.434; 95% CI, 0.376-0.502) and ICU mortality (HR, 0.296; 95% CI, 0.251-0.349). Such association may act differently for patients with different fluid balance (P value for interaction < .001). LD use is associated with lower hospital and ICU mortality in CS-AKI patients in general. Patients under different conditions showed diverse responses toward such treatment indicating that personalized management is needed.

Abstract 14823: Assessment of the Appropriateness and Prognostic Significance of the Current Universal Diagnostic Definition for Acute Kidney Injury in Patients After Cardiac Surgery and Exploration of Tailored Criteria

Background: Cardiac surgery-associated AKI (CSA-AKI) is prevalent and its diagnosis currently adheres to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, commonly used criteria developed for general populations. Limited evidence exists on their appropriateness and prognostic value for CSA-AKI, which exhibits unique mechanisms and clinical courses. Aims: We aimed to assess the prognostic value of the KDIGO diagnostic criteria for CSA-AKI and explore potentially more prognostically relevant criteria for cardiac surgery. Methods: Patients undergoing coronary artery bypass grafting surgery at a single institution were included and categorized into four groups: no AKI, AKI stage-1, AKI stage-2, and AKI stage-3, based on KDIGO guidelines. Patients of AKI-1 were further divided based on specific criteria met: absolute criteria (0.3mg/dL serum creatinine (SCr) increase over 48-hour intervals), ratio criteria (1.5-1.9 times baseline SCr), and dual criteria (meeting both criteria) AKI-1. The primary outcome was 30-day all-cause mortality. Results: Among 20626 patients, the overall incidence of CSA-AKI was 47.4%, with rates of 44.2% for AKI-1, 2.2% for AKI-2, and 0.9% for AKI-3. The overall 30-day mortality was 0.6%. Among AKI-1, 72.4%, 3.2%, and 24.2% met the absolute criteria, ratio criteria, and dual criteria, respectively. After multivariate adjustment, AKI-2 and AKI-3 were significantly associated with increased 30-day mortality. However, neither AKI-1 nor its subcategories showed prognostic significance. Subsequent restricted cubic spline analysis identified more prognostically relevant cut-off values for AKI-1 criteria as &gt;0.7 mg/dL SCr increase over 48-hour intervals and &gt;1.3 times baseline SCr, respectively. Conclusions: The current universal KDIGO diagnostic criteria may not be suitable for CSA-AKI, especially regarding cut-off values for AKI stage-1, highlighting the necessity of tailored criteria for cardiac surgery.

Predicting pediatric cardiac surgery-associated acute kidney injury using machine learning.

Prediction of cardiac surgery-associated acute kidney injury (CS-AKI) in pediatric patients is crucial to improve outcomes and guide clinical decision-making. This study aimed to develop a supervised machine learning (ML) model for predicting moderate to severe CS-AKI at postoperative day 2 (POD2). This retrospective cohort study analyzed data from 402 pediatric patients who underwent cardiac surgery at a university-affiliated children's hospital, who were separated into an 80%-20% train-test split. The ML model utilized demographic, preoperative, intraoperative, and POD0 clinical and laboratory data to predict moderate to severe AKI categorized by Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 or 3 at POD2. Input feature importance was assessed by SHapley Additive exPlanations (SHAP) values. Model performance was evaluated using accuracy, area under the receiver operating curve (AUROC), precision, recall, area under the precision-recall curve (AUPRC), F1-score, and Brier score. Overall, 13.7% of children in the test set experienced moderate to severe AKI. The ML model achieved promising performance, with accuracy of 0.91 (95% CI: 0.82-1.00), AUROC of 0.88 (95% CI: 0.72-1.00), precision of 0.92 (95% CI: 0.70-1.00), recall of 0.63 (95% CI: 0.32-0.96), AUPRC of 0.81 (95% CI: 0.61-1.00), F1-score of 0.73 (95% CI: 0.46-0.99), and Brier score loss of 0.09 (95% CI: 0.00-0.17). The top ten most important features assessed by SHAP analyses in this model were preoperative serum creatinine, surgery duration, POD0 serum pH, POD0 lactate, cardiopulmonary bypass duration, POD0 vasoactive inotropic score, sex, POD0 hematocrit, preoperative weight, and POD0 serum creatinine. A supervised ML model utilizing demographic, preoperative, intraoperative, and immediate postoperative clinical and laboratory data showed promising performance in predicting moderate to severe CS-AKI at POD2 in pediatric patients.

Alterations to Kidney Physiology during Cardiopulmonary Bypass-A Narrative Review of the Literature and Practical Remarks.

According to different authors, cardiac surgery-associated acute kidney injury (CSA-AKI) incidence can be as high as 20-50%. This complication increases postoperative morbidity and mortality and impairs long-term kidney function in some patients. This review aims to summarize current knowledge regarding alterations to renal physiology during cardiopulmonary bypass (CPB) and to discuss possible nephroprotective strategies for cardiac surgeries. Relevant sections: Systemic and renal circulation, Vasoactive drugs, Fluid balance and Osmotic regulation and Inflammatory response. Considering the available scientific evidence, it is concluded that adequate kidney perfusion and fluid balance are the most critical factors determining postoperative kidney function. By adequate perfusion, one should understand perfusion with proper oxygen delivery and sufficient perfusion pressure. Maintaining the fluid balance is imperative for a normal kidney filtration process, which is essential for preserving the intra- and postoperative kidney function. The review of the available literature regarding kidney function during cardiac surgery revealed a need for a more holistic approach to this subject.

Elevated glycosylated hemoglobin levels are associated with severe acute kidney injury following coronary artery bypass surgery

BackgroundDiabetic patients are at increased risk of acute kidney injury (AKI) following surgery. The significance of uncontrolled diabetes on kidney function after coronary artery bypass grafting (CABG) remains controversial. Our aim was to study the association between pre-operative hemoglobin A1c (HbA1c) and severe cardiac surgery-associated AKI (CSA-AKI) following CABG. MethodsA single-center, retrospective cohort study including patients who underwent isolated CABG from 2010 to 2018 was performed. Patients were grouped into pre-operative HbA1c of <6.5 %, 6.5–8.5 %, and ≥8.5 %. Postoperative serum creatinine levels were queried for up to 30 days, and the 30-day risk of severe AKI was compared among groups. Multivariable logistic regression was used to study factors associated with severe CSA-AKI and the association of severe CSA-AKI with postoperative outcomes. Cox regression was used to study the association between severe CSA-AKI and all-cause mortality from the time of surgery to the last follow-up or death. ResultsA total of 2424 patients met the inclusion criteria. Patients were primarily male (70.5 %), with a median age of 64 years (IQR 57–71). Median bypass and cross-clamp times were 95 (IQR 78–116) and 78 min (IQR 63–95). Severe CSA-AKI occurred within 30 days in 5.7 %, 6.7 %, and 9.1 % of patients with pre-op HbA1c of <6.5 %, 6.5–8.5 %, and ≥8.5 %, respectively. After adjusting for covariates, HbA1c >8.5 %, was independently associated with severe CSA-AKI 30 days after CABG (aOR 1.59, 95%CI 1.06–2.40). In addition, severe CSA-AKI was associated with increased 30- (aOR 15.83,95%CI 7.94–31.56) and 90- day mortality (aOR 9.54, 95%CI 5.46–16.67), prolonged length of stay (aOR 3.46,95%CI 2.41–4.96) and unplanned 30-day readmission (aOR 2.64, 95%CI 1.77–3.94). Lastly, severe CSA-AKI was associated with increased all-cause mortality (aHR 3.19, 95%CI 2.43–4.17). ConclusionElevated preoperative HbA1c (≥8.5 %) was independently associated with an increased 30-day risk of severe CSA-AKI, which is a consistent predictor of adverse outcomes after CABG. Delaying surgery to achieve optimal glycemic control in an elective setting may be reasonable.

Cardiac surgery-Associated acute kidney injury - A narrative review.

Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) is a serious complication seen in approximately 20-30% of cardiac surgery patients. The underlying pathophysiology is complex, often involving both patient- and procedure related risk factors. In contrast to AKI occurring after other types of major surgery, the use of cardiopulmonary bypass comprises both additional advantages and challenges, including non-pulsatile flow, targeted blood flow and pressure as well as the ability to manipulate central venous pressure (congestion). With an increasing focus on the impact of CSA-AKI on both short and long-term mortality, early identification and management of high-risk patients for CSA-AKI has evolved. The present narrative review gives an up-to-date summary on definition, diagnosis, underlying pathophysiology, monitoring and implications of CSA-AKI, including potential preventive interventions. The review will provide the reader with an in-depth understanding of how to identify, support and provide a more personalized and tailored perioperative management to avoid development of CSA-AKI.

Weekend effect on the incidence and outcomes of cardiac surgery associated - acute kidney injury

BackgroundThe effects of surgical day (workdays or weekends) on occurrence and outcome of cardiac surgery associated -acute kidney injury (CSA-AKI) remains unclear. This study aimed to compare the incidence and short-term outcomes of CSA-AKI in patients undergoing surgery on workdays and weekends.Materials and methodsPatients who underwent cardiac surgery from July 2020 to December 2020 were retrospectively enrolled in this study. These patients were divided into a weekend group and workday group. The primary endpoint was the incidence of CSA-AKI. The secondary endpoints included renal function recovery and in-hospital mortality. The logistic regression model was used to explore the risk factors for CSA-AKI. Stratification analysis was performed to estimate the association between CSA-AKI and weekend surgery stratified by emergency surgery.ResultsA total of 1974 patients undergoing cardiac surgery were enrolled. The incidence of CSA-AKI in the weekend group was significantly higher than that in the workday group (42.8% vs. 34.7%, P = 0.038). Further analysis of patients with CSA-AKI showed that there was no difference in renal function recovery between the workday AKI group and weekend AKI group. There was no difference in in-hospital mortality between the weekend group and workday group (3.6% vs. 2.4%, P = 0.327); however, the in-hospital mortality of the weekend AKI group was significantly higher than that of the workday AKI group (8.5% vs. 2.9%, P = 0.014). Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. The multiplicative model showed an interaction between weekend surgery and emergency surgery; weekend surgery was related to an increased risk of AKI among patients undergoing emergency surgery [adjusted OR (95% CI): 1.96 (1.012-8.128)].ConclusionsThe incidence of CSA-AKI in patients undergoing cardiac surgery on weekends was significantly higher compared to that in patients undergoing cardiac surgery on workdays. Weekend surgery did not affect the in-hospital mortality of all patients but significantly increased the mortality of AKI patients. Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. Weekend emergency surgery significantly increased the risk of CSA-AKI.