Cardiac Surgery-associated Acute Kidney Injury Research Articles

Assessment of Individualized Mean Perfusion Pressure Target for Cardiac Surgery-Associated AKI: PrevHemAKI Trial

Assessment of Individualized Mean Perfusion Pressure Target for Cardiac Surgery-Associated AKI: PrevHemAKI Trial

Prevent Cardiac Surgery-Associated AKI by Perioperative Implementation of Care Bundles

Prevent Cardiac Surgery-Associated AKI by Perioperative Implementation of Care Bundles

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.

Predicting acute kidney injury with an artificial intelligence-driven model in a pediatric cardiac intensive care unit

BackgroundAcute kidney injury (AKI) is among the most common complications following cardiac surgery in adult and pediatric patients, significantly affecting morbidity and mortality. Artificial Intelligence (AI) with Machine Learning (ML) can be used to predict outcomes. AKI diagnosis anticipation may be an ideal target of these methods. The scope of the study is building a Machine Learning (ML) train model with Random Forest (RF) algorithm, based on electronic health record (EHR) data, able to forecast AKI continuously after 48 h in post-cardiac surgery children, and to test its performance.Four hundred nineteen consecutive patients out of 1115 hospital admissions were enrolled in a single-center retrospective study. Patients were younger than 18 years and admitted from August 2018 to February 2020 in a pediatric cardiac intensive care unit (PCICU) undergoing cardiac surgery, invasive procedure (hemodynamic studies), and medical conditions with complete EHR records and discharged after 48 h or more.ResultsThirty-six variables were selected to build the algorithm according to commonly described cardiac surgery-associated AKI clinical predictors. We evaluated different models for different outcomes: binary AKI (no AKI vs. AKI), severe AKI (no-mild vs severe AKI), and multiclass classification (maximum AKI and the most frequent level of AKI, mode AKI). The algorithm performance was assessed with the area under the curve receiver operating characteristics (AUC ROC) for binary classification, with accuracy and K for multiclass classification. AUC ROC for binary AKI was 0.93 (95% CI 0.92–0.94), and for severe AKI was 0.99 (95% CI 0.98–1). Mode AKI accuracy was 0.95, and K was 0.80 (95% CI 0.94–0.96); maximum AKI accuracy was 0.92, and K was 0.71 (95% CI 0.91–0.93). The importance matrix plot demonstrated creatinine, basal creatinine, platelets count, adrenaline support, and lactate dehydrogenase for binary AKI with the addition of cardiopulmonary bypass duration for severe AKI as the most relevant variables of the model.ConclusionsWe validated a ML model to detect AKI occurring after 48 h in a retrospective observational study that could help clinicians in individuating patients at risk of AKI, in which a preventive strategy can be determinant to improve the occurrence of renal dysfunction.

The Association Between Serum Glutathione Peroxidase-3 Concentration and Risk of Acute Kidney Injury After Cardiac Surgery: A Nested Case-Control Study

Oxidative stress has an integral role in the pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Glutathione peroxidase 3 (GPx3) is an important antioxidant enzyme in circulation and is mainly secreted by the kidney. This study aimed to evaluate the relation between GPx3 protein and CSA-AKI. This study is a nested case-control study in Zhongshan Hospital affiliated with Fudan University. We examined serum samples from 80 CSA-AKI patients and 80 age- and gender-matched non-AKI patients who underwent cardiac surgery. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria. We measured serum GPx3 concentration using the enzyme-linked immunosorbent assay. GPx3 ratio is the ratio of preoperative and 6hours postoperative of GPx3 protein concentration. We applied dose-response relation analyses to odds ratio in different GPx3 ratio levels and integrated it into the logistic model to predict the risk of AKI. The receiver operating characteristic curve and area under the curve (AUC) was used to assess the prediction models. Postoperative serum GPx3 concentrations were significantly lower in the AKI group compared with the non-AKI group (1.78±0.33 vs 2.03±0.27, p<0.001). Malondialdehyde was higher in the AKI than in the non-AKI group (17.74±8.65 vs 7.48±4.59, p<0.001). The AKI risk increased in a dose-dependent manner, which was flat in the first half of the GPx3 ratio and then tended to be faster. The peaking odds ratio of CSA-AKI was 2.615 at the GPx3 ratio of 1.21 to 1.40. The AUC value to predict CSA-AKI only included the GPx3 ratio was 72.3%. After gradually integrating other covariates (body mass index, aortic crossclamp time, and cardiopulmonary bypass), the model showed an AUC of 82.6%. The serum GPx3 concentration was significantly lower in the CSA-AKI group. GPx3 ratio has a good predictive value for CSA-AKI, which may be a potential early diagnostic marker for AKI.

Could plasma viscosity play a role in cardiac-surgery associated acute kidney injury?

Could plasma viscosity play a role in cardiac-surgery associated acute kidney injury?

The impact of statin use before intensive care unit admission on patients with acute kidney injury after cardiac surgery.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery. The influence of statin use before surgery on the renal outcome of patients undergoing cardiac surgery is controversial. The purpose of this study was to evaluate the effect of statins on postoperative renal outcomes in patients undergoing cardiac surgery. Methods: We included CSA-AKI patients in the Medical Information Mart for Intensive Care (MIMIC)-IV database and were divided into statin group and non-statin group according to whether they used statins before entering intensive care units (ICU). The main outcomes were hospitalization and 30-day mortality, and the secondary outcomes were 60-day mortality and 90-day mortality. We used propensity score matching (PSM) to adjust for confounding factors. The 95% confidence interval (CI) and risk ratio (RO) were calculated by the COX proportional regression model. At the same time, stratified analysis was used to explore whether the relationship between the statins use before intensive care units and mortality was different in each subgroup and whether the relationship between different doses of Atorvastatin and mortality was different. Result: We identified 675 pre-ICU statin users and 2095 non-statin users. In the COX proportional regression model, pre-ICU statin use was associated with decreased in-hospital (HR = 0.407, 95%confidence interval 0.278-0.595, p < 0.001) and 30-day mortality (HR = 0.407, 95%CI 0.279-0.595, p < 0.001). The survival rate of patients who took statins before entering ICU was significantly higher than that of those who did not use statins at 30days, 60days and 90days. There is a significant interaction between patients with aged>65years (HR = 0.373, 95%CI 0.240-0.581, p < 0.001), Acute kidney injury grade I (HR = 0.244, 95%CI 0.118-0.428, p < 0.001), and without post-myocardial infarction syndrome (HR = 0.344, 95%CI 0.218-0.542, p < 0.001). The mortality in hospital and 60days of CSA-AKI patients treated with ≥80mg Atorvastatin before operation was significantly reduced (p < 0.05). Conclusion: The pre-ICU statin use was significantly associated with decreased risk in hospital and 30-day mortality. The preoperative use of ≥80mg Atorvastatin may improve the prognosis of CSA-AKI.

Cardiac surgery-associated acute kidney injury and perioperative plasma viscosity: is there a relationship?

Plasma viscosity (PV) is a key factor in microcirculatory flow resistance and capillary perfusion during hemodilution, we hypothesized a possible relationship between cardiac surgery-associated acute kidney injury (CSA-AKI) and PV. We conducted a prospective, observational, single-center study on 50 adult cardiac surgery patients with cardiopulmonary bypass (age 64 years, male sex 80%, baseline serum creatinine 1.04mg/dL). We assessed perioperative characteristics, management, short-term outcomes, blood analysis, PV, serum creatinine, and diuresis. CSA-AKI was identified using KDIGO criteria. Data were collected at 10 time points during the first perioperative week. CSA-AKI occurred in 17 patients (34%): 12 (24%) stage 1, 1 (2%) stage 2, and 4 (8%) stage 3. Most patients (88%) developed CSA-AKI within 48h post-surgery. Patients with CSA-AKI had higher body mass index (BMI), more frequent chronic kidney disease (CKD), and lower hemoglobin and hematocrit levels. The median baseline PV for the entire cohort was 1.50 cP on EDTA and 1.37 cP on citrate. No significant differences in PV levels were found between patients with CSA-AKI and normal kidney function, both at baseline and at the 48-h. Logistic and Cox regression analyses showed no significant relationship between PV and CSA-AKI. However, CSA-AKI was related to increased BMI, lower hemoglobin and hematocrit levels, and pre-existing CKD. The present study found no significant association between PV and CSA-AKI. Nevertheless, more research is needed to validate this finding and to investigate the role of PV in other clinical settings.

Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury.

Acute kidney injury(AKI) occurs frequently after infant cardiac surgery and is associated with poor outcomes, including mortality and prolonged length of stay. AKI mechanisms are poorly understood, limiting therapeutic targets. Emerging data implicates dysregulated immune activation in post-cardiac surgery AKI development. We sought to identify immune-mediated AKI biomarkers after infant cardiopulmonary bypass (CPB)-assisted cardiac surgery. A single-center prospective study of 126 infants less than 1year old undergoing CPB-assisted surgery enrolled between 10/2017 and 6/2019. Urine samples were collected before CPB and at 6, 24, 48, and 72h after surgery. Immune-mediated biomarkers were measured using commercial ELISA and Luminex™ multiplex kits. Based on subject age, neonatal KDIGO (< 1month) or KDIGO criteria defined AKI. The Kruskal-Wallis rank test determined the relationship between urinary biomarker measurements and AKI. A total of 35 infants (27%) developed AKI. AKI subjects were younger, underwent more complex surgery, and had longer CPB time. Subjects with AKI vs. those without AKI had higher median urinary chemokine 10 (C-X-C motif) ligand levels at 24, 48, and 72h, respectively: 14.3pg/ml vs. 5.3pg/ml, 3.4pg/ml vs. 0.8pg/ml, and 1.15pg/ml vs. 0.22pg/ml (p < 0.05) post-CPB. At 6h post-CPB, median vascular cell adhesion protein 1 (VCAM) levels (pg/mL) were higher among AKI subjects (491pg/ml vs. 0pg/ml, p = 0.04). Urinary CXCL10 and VCAM are promising pro-inflammatory biomarkers for early AKI detection and may indicate eventual AKI therapeutic targets. A higher resolution version of the Graphical abstract is available as Supplementary information.

Development, External Validation, and Visualization of Machine Learning Models for Predicting Occurrence of Acute Kidney Injury after Cardiac Surgery.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication that results in short- and long-term mortality among patients. Here, we adopted machine learning algorithms to build prediction models with the overarching goal of identifying patients who are at a high risk of such unfavorable kidney outcomes. A total of 1686 patients (development cohort) and 422 patients (validation cohort), with 126 pre- and intra-operative variables, were recruited from the First Medical Centre and the Sixth Medical Centre of Chinese PLA General Hospital in Beijing, China, respectively. Analyses were performed using six machine learning techniques, namely K-nearest neighbor, logistic regression, decision tree, random forest (RF), support vector machine, and neural network, and the APPROACH score, a previously established risk score for CSA-AKI. For model tuning, optimal hyperparameter was achieved by using GridSearch with 5-fold cross-validation from the scikit-learn library. Model performance was externally assessed via the receiver operating characteristic (ROC) and decision curve analysis (DCA). Explainable machine learning was performed using the Python SHapley Additive exPlanation (SHAP) package and Seaborn library, which allow the calculation of marginal contributory SHAP value. 637 patients (30.2%) developed CSA-AKI within seven days after surgery. In the external validation, the RF classifier exhibited the best performance among the six machine learning techniques, as shown by the ROC curve and DCA, while the traditional APPROACH risk score showed a relatively poor performance. Further analysis found no specific causative factor contributing to the development of CSA-AKI; rather, the development of CSA-AKI appeared to be a complex process resulting from a complex interplay of multiple risk factors. The SHAP summary plot illustrated the positive or negative contribution of RF-top 20 variables and extrapolated risk of developing CSA-AKI at individual levels. The Seaborn library showed the effect of each single feature on the model output of the RF prediction. Efficient machine learning approaches were successfully established to predict patients with a high probability of developing acute kidney injury after cardiac surgery. These findings are expected to help clinicians to optimize treatment strategies and minimize postoperative complications. The study protocol was registered at the ClinicalTrials Registration System (https://www.clinicaltrials.gov/, #NCT04966598) on July 26, 2021.

Molecular hydrogen: prospective treatment strategy of kidney damage after cardiac surgery.

Cardiac surgery-associated acute kidney injury is a common post-operative complication, mostly due to increasing oxidative stress. Recently, molecular hydrogen (H2 gas) has also been applied to cardiac surgery due to its ability to reduce oxidative stress. We evaluated the potential effect of H2 application on the kidney in an in vivo model of simulated heart transplantation. Pigs underwent cardiac surgery within 3 h while connected to extracorporeal circulation (ECC) and subsequent 60 min of spontaneous reperfusion of the heart. We used two experimental groups: T-pigs after transplantation and TH-pigs after transplantation treated with 4% H2 mixed with air during inhalation of anesthesia and throughout oxygenation of blood in ECC. The levels of creatinine, urea and phosphorus were measured in plasma. Renal tissue samples were analyzed by Western blot method for protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1), and superoxide dismutase (SOD1). After cardiac surgery, selected plasma biomarkers were elevated. However, H2 therapy was followed by the normalization of all these parameters. Our results suggest activation of Nrf2/Keap1 pathway as well as increased SOD1 protein expression in the group treated with H2. The administration of H2 had a protective effect on the kidneys of pigs after cardiac surgery, especially in terms of normalization of plasma biomarkers to control levels.

#3259 ARTEMIS: A PHASE 3 STUDY OF RAVULIZUMAB TO PROTECT PATIENTS WITH CKD UNDERGOING CARDIAC SURGERY FROM AKI AND SUBSEQUENT MAJOR ADVERSE KIDNEY EVENTS

Abstract Background and Aims In patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), pre-existing chronic kidney disease (CKD) confers a substantial risk for poor outcomes, including the development of cardiac surgery-associated acute kidney injury (CSA-AKI). CSA-AKI occurs in ≥50% of patients with CKD undergoing cardiac surgery with CPB vs ∼20–25% of patients without CKD1,2. The risk of subsequent Major Adverse Kidney Events (MAKE; a composite of sustained kidney dysfunction, initiation of dialysis, and death) is also elevated in patients with CKD. Causes of CSA-AKI are multifactorial and complex, and may include inflammation, oxidative stress, renal congestion, and ischaemic injury (such as ischaemic-reperfusion injury [IRI]). IRI is a common cause of AKI and typically results from early hypoperfusion while on bypass, followed by kidney injury upon reperfusion. There are currently no approved therapies that reduce the risk of AKI and associated poor outcomes after cardiac surgery with CPB3. Preclinical and clinical studies suggest that damage and inflammation caused by IRI and CPB is amplified by complement activation3; early treatment with C5 inhibitors, especially before onset of ischaemia, may lower the risk of damage. Method ARTEMIS is a Phase 3, randomised, double-blind, placebo-controlled, multicentre study of ravulizumab in adults with CKD and stable cardiac disease undergoing non-emergent sternotomy with CPB, to reduce the risk of post-operative AKI and subsequent MAKE 90 days post-surgery. Key inclusion and exclusion criteria can be found in Figure 1 and a study schematic in Figure 2. Briefly, the study consists of an up to 28-day screening period, randomisation and dosing 1–7 days prior to surgery with CPB (Day 1), a 90-day primary evaluation period post-CPB, and a survival follow-up at day 365 post-CPB. Approximately 736 participants will be randomised 1:1 to receive a single weight-based dose of ravulizumab or placebo; randomisation will be based on baseline CKD stage (3A, 3B, 4) and surgery type (mitral valve replacement or combined procedures vs other single procedures). The primary objective of this study is to assess the efficacy of ravulizumab in reducing the risk of MAKE90, defined as meeting ≥1 of the following by day 90 post-CPB: ≥25% sustained decrease from baseline in estimated glomerular filtration rate (calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, based on serum Cystatin C); initiation of renal replacement therapy; death from any cause. The safety of ravulizumab in participants with CKD undergoing non-emergent CPB will also be evaluated. Other secondary objectives include assessment of ravulizumab efficacy for reducing AKI (based on serum creatinine) and MAKE risk at earlier timepoints following CPB, alongside any effects it may have on healthcare resource utilisation and health-related quality of life – as well as treatment immunogenicity – in participants with CKD undergoing non-emergent CPB. Results The final analysis will be conducted when all participants have completed the primary evaluation period. Conclusion The aim of this study is to assess whether terminal complement inhibition with ravulizumab is safe and effective in reducing kidney injury and improving outcomes in patients with CKD undergoing cardiac surgery with CPB.

Adult Cardiac Surgery-Associated Acute Kidney Injury: Joint Consensus Report

Acute kidney injury (AKI) is increasingly recognized as a source of poor patient outcomes after cardiac surgery. The purpose of the present report is to provide perioperative teams with expert recommendations specific to cardiac surgery-associated AKI (CSA-AKI). This report and consensus recommendations were developed during a joint, in-person, multidisciplinary conference with the Perioperative Quality Initiative and the Enhanced Recovery After Surgery Cardiac Society. Multinational practitioners with diverse expertise in all aspects of cardiac surgical perioperative care, including clinical backgrounds in anesthesiology, surgery and nursing, met from October 20 to 22, 2021, in Sacramento, California, and used a modified Delphi process and a comprehensive review of evidence to formulate recommendations. The quality of evidence and strength of each recommendation were established using the Grading of Recommendations Assessment, Development, and Evaluation methodology. A majority vote endorsed recommendations. Based on available evidence and group consensus, a total of 13 recommendations were formulated (4 for the preoperative phase, 4 for the intraoperative phase, and 5 for the postoperative phase), and are reported here. Because there are no reliable or effective treatment options for CSA-AKI, evidence-based practices that highlight prevention and early detection are paramount. Cardiac surgery-associated AKI incidence may be mitigated and postsurgical outcomes improved by focusing additional attention on presurgical kidney health status; implementing a specific cardiopulmonary bypass bundle; using strategies to maintain intravascular euvolemia; leveraging advanced tools such as the electronic medical record, point-of-care ultrasound, and biomarker testing; and using patient-specific, goal-directed therapy to prioritize oxygen delivery and end-organ perfusion over static physiologic metrics.

Genetic predisposition may not improve prediction of cardiac surgery-associated acute kidney injury.

Background: The recent integration of genomic data with electronic health records has enabled large scale genomic studies on a variety of perioperative complications, yet genome-wide association studies on acute kidney injury have been limited in size or confounded by composite outcomes. Genome-wide association studies can be leveraged to create a polygenic risk score which can then be integrated with traditional clinical risk factors to better predict postoperative complications, like acute kidney injury. Methods: Using integrated genetic data from two academic biorepositories, we conduct a genome-wide association study on cardiac surgery-associated acute kidney injury. Next, we develop a polygenic risk score and test the predictive utility within regressions controlling for age, gender, principal components, preoperative serum creatinine, and a range of patient, clinical, and procedural risk factors. Finally, we estimate additive variant heritability using genetic mixed models. Results: Among 1,014 qualifying procedures at Vanderbilt University Medical Center and 478 at Michigan Medicine, 348 (34.3%) and 121 (25.3%) developed AKI, respectively. No variants exceeded genome-wide significance (p < 5 × 10-8) threshold, however, six previously unreported variants exceeded the suggestive threshold (p < 1 × 10-6). Notable variants detected include: 1) rs74637005, located in the exonic region of NFU1 and 2) rs17438465, located between EVX1 and HIBADH. We failed to replicate variants from prior unbiased studies of post-surgical acute kidney injury. Polygenic risk was not significantly associated with post-surgical acute kidney injury in any of the models, however, case duration (aOR = 1.002, 95% CI 1.000-1.003, p = 0.013), diabetes mellitus (aOR = 2.025, 95% CI 1.320-3.103, p = 0.001), and valvular disease (aOR = 0.558, 95% CI 0.372-0.835, p = 0.005) were significant in the full model. Conclusion: Polygenic risk score was not significantly associated with cardiac surgery-associated acute kidney injury and acute kidney injury may have a low heritability in this population. These results suggest that susceptibility is only minimally influenced by baseline genetic predisposition and that clinical risk factors, some of which are modifiable, may play a more influential role in predicting this complication. The overall impact of genetics in overall risk for cardiac surgery-associated acute kidney injury may be small compared to clinical risk factors.

Predictive value of urinary cell cycle arrest biomarkers for all cause-acute kidney injury: a meta-analysis

The cell cycle arrest markers tissue inhibitor metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as potential biomarkers of acute kidney injury (AKI) in critically ill adults in intensive care units and cardiac surgery-associated AKI (CSA-AKI). However, the clinical impact on all-cause AKI remains unclear. Here, we report a meta-analysis performed to evaluate the predictive value of this biomarker for all-cause AKI. The PubMed, Cochrane, and EMBASE databases were systematically searched up to April 1, 2022. We used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted useful information from these studies and calculated the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Twenty studies with 3625 patients were included in the meta-analysis. The estimated sensitivity of urinary [TIMP-2] × [IGFBP7] in the diagnosis of all-cause AKI was 0.79 (95% CI 0.72, 0.84), and the specificity was 0.70 (95% CI 0.62, 0.76). The value of urine [TIMP-2] × [IGFBP7] in the early diagnosis of AKI was assessed using a random effects model. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 2.6 (95% CI 2.1, 3.3), 0.31 (95% CI 0.23, 0.40), and 8 (95% CI 6, 13), respectively. The AUROC was 0.81 (95% CI 0.78–0.84). No significant publication bias was observed in eligible studies. Subgroup analysis indicated that the diagnostic value was related to the severity of AKI, time measurement, and clinical setting. This study shows that urinary [TIMP-2] × [IGFBP7] is a reliable effective predictive test for all cause-AKI. However, whether and how urinary [TIMP-2] × [IGFBP7] can be used in clinical diagnosis still requires further research and clinical trials.

Dynamic cellular changes in acute kidney injury caused by different ischemia time

Ischemia reperfusion injury (IRI), often related to surgical procedures, is one of the important causes of acute kidney injury (AKI). To decipher the dynamic process of AKI caused by IRI (with prolonged ischemia phase), we performed single-cell RNA sequencing (scRNA-seq) of clinically relevant IRI murine model with different ischemic intervals. We discovered that Slc5a2hi proximal tubular cells were susceptible to AKI and highly expressed neutral amino acid transporter gene Slc6a19, which was dramatically decreased over the time course. With the usage of mass spectrometry-based metabolomic analysis, we detected that the level of neutral amino acid isoleucine dropped off in AKI mouse plasma metabolites. And the reduction of plasma isoleucine was also verified in patients with cardiac surgery-associated acute kidney injury (CSA-AKI). The findings advanced the understanding of dynamic process of AKI and introduced reduction of isoleucine as a potential biomarker for CSA-AKI.

Metabolomic interplay between gut microbiome and plasma metabolome in cardiac surgery-associated acute kidney injury.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a prevalent complication of cardiac surgery, which may be associated with a great risk of developing chronic kidney disease and mortality. This study aimed to investigate the possible links between gut microbiota metabolism and CSA-AKI. A prospective cohort of patients who underwent cardiac surgery was continuously recruited, who were further divided into CSA-AKI group and Non-AKI group based on clinical outcomes. Their faecal and plasma samples were collected before surgery and were separately analysed by nontargeted and targeted metabolomics. The differential metabolites related to CSA-AKI were screened out using statistical methods, and altered metabolic pathways were determined by examining the Kyoto Encyclopedia of Genes and Genomes database. Nearly 1000 faecal metabolites were detected through high-resolution mass spectrometry (MS) and bioinformatics at high and mid confidence levels, and 49 differential metabolites at high confidence level may perform essential biological functions and provide potential diagnostic indicators. Compared with the Non-AKI group, the patients in the CSA-AKI group displayed dramatic changes in gut microbiota metabolism, including amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism and ATP-binding cassette (ABC) transporters. Meanwhile, 188 plasma metabolites were identified and quantified by tandem MS, and 34 differential plasma metabolites were screened out between the two groups using univariate statistical analysis. These differential plasma metabolites were primarily enriched in the following metabolic pathways: sulphur metabolism, amino acid biosynthesis, tryptophan metabolism and ABC transporters. Furthermore, the content of indole metabolites in the faecal and plasma samples of the CSA-AKI group was higher than that of the Non-AKI group. Patients with CSA-AKI may have dysbiosis of their intestinal microbiota and metabolic abnormalities in their gut system before cardiac surgery. Thus, some metabolites and related metabolic pathways may be potential biomarkers and new therapeutic targets for the disease.

Evaluation of the contribution of gut microbiome dysbiosis to cardiac surgery-associated acute kidney injury by comparative metagenome analysis.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common hospital-acquired AKI that carries a grave disease burden. Recently, gut-kidney crosstalk has greatly changed our understanding of the pathogenesis of kidney diseases. However, the relationship between gut microbial dysbiosis and CSA-AKI remains unclear. The purpose of this study was to investigate the possible contributions of gut microbiota alterations in CSA-AKI patients. Patients undergoing cardiac surgery were enrolled and divided into acute kidney injury (AKI) and Non_AKI groups. Faecal samples were collected before the operation. Shotgun metagenomic sequencing was performed to identify the taxonomic composition of the intestinal microbiome. All groups were statistically compared with alpha- and beta-diversity analysis, and linear discriminant analysis effect size (LEfSe) analysis was performed. A total of 70 individuals comprising 35 AKI and 35 Non_AKI were enrolled in the study. There was no significant difference between the AKI and Non_AKI groups with respect to the alpha-and beta-diversity of the Shannon index, Simpson or Chao1 index values except with respect to functional pathways (p < 0.05). However, the relative abundance of top 10 gut microbiota in CSA-AKI was different from the Non_AKI group. Interestingly, both LEfSe and multivariate analysis confirmed that the species Escherichia coli, Rothia mucilaginosa, and Clostridium innocuum were associated with CSA-AKI. Moreover, correlation heat map indicated that altered pathways and disrupted function could be attributed to disturbances of gut microbiota involving Escherichia coli. Dysbiosis of the intestinal microbiota in preoperative stool affects susceptibility to CSA-AKI, indicating the crucial role of key microbial players in the development of CSA-AKI. This work provides valuable knowledge for further study of the contribution of gut microbiota in CSA-AKI.

Outcomes associated with unrecognized acute kidney injury in postoperative pediatric cardiac patients.

The present retrospective study was carried out to determine the incidence of unrecognized cardiac surgery-associated acute kidney injury (CSA-AKI) due to infrequency of serum creatinine (SCr) measurements in pediatric cardiac patients and to assess the association between unrecognized CSA-AKI and clinical outcomes. This study was a single-center, retrospective study of pediatric patients who underwent cardiac surgery. Patients were diagnosed with CSA-AKI based on SCr measurements, and unrecognized CSA-AKI was defined under the assumptions that there had been only one or two SCr measurements within 48h after surgery: CSA-AKI unrecognized by one SCr measurement (AKI-URone), CSA-AKI unrecognized by two SCr measurements (AKI-URtwo), and CSA-AKI recognized by one and two SCr measurements (AKI-R). The change of SCr from baseline to postoperative day 30 (delta SCr30d) was assessed as a surrogate of kidney recovery. In a total of 557 cases, 313 patients (56.2%) were diagnosed with CSA-AKI, 188 (33.8%) of whom had unrecognized CSA-AKI. Delta SCr30d in the AKI-URtwo group and delta SCr30d in the AKI-URone group was not significantly different from delta SCr30d in the non-AKI group (p = 0.67 and p = 0.79, respectively). There were significant differences in the durations of mechanical ventilation, serum B-type natriuretic peptide levels, and lengths of stay in hospital between the non-AKI group and the AKI-URtwo group and between the non-AKI group and the AKI-URtwo group. Unrecognized CSA-AKI due to infrequent SCr measurements is not rare and is associated with prolonged mechanical ventilation, high postoperative BNP level, and prolonged length of stay in hospital. A higher resolution version of the Graphical abstract is available as Supplementary information.