Increased numbers of pre-operative circulating monocytes predict risk of developing cardiac surgery-associated acute kidney injury in conditions requiring cardio pulmonary bypass.

BACKGROUND: Evaluating patients' risk for acute kidney injury (AKI) is crucial for positive outcomes following cardiac surgery. Our aims were first to select candidate risk factors from pre- or intra-operative real-world parameters collected from routine medical care and then evaluate potential associations between those parameters and risk of onset of post-operative cardiac surgery-associated AKI (CSA-AKI). METHOD: We conducted two cohort studies in Japan. The first was a single-center prospective cohort study (n = 145) to assess potential association between 115 clinical parameters collected from routine medical care and CSA-AKI (≥ Stage1) risk in the population of patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB). To select candidate risk factors, we employed random forest analysis and applied survival analyses to evaluate association strength. In a second retrospective cohort study, we targeted patients undergoing cardiac surgery with CPB (n = 619) and evaluated potential positive associations between CSA-AKI incidence and risk factors suggested by the first cohort study. RESULTS: Variable selection analysis revealed that parameters in clinical categories such as circulating inflammatory cells, CPB-related parameters, ventilation, or aging were potential CSA-AKI risk factors. Survival analyses revealed that increased counts of pre-operative circulating monocytes and neutrophils were associated with CSA-AKI incidence. Finally, in the second cohort study, we found that increased pre-operative circulating monocyte counts were associated with increased CSA-AKI incidence. CONCLUSIONS: Circulating monocyte counts in the pre-operative state are associated with increased risk of CSA-AKI development. This finding may be useful in stratifying patients for risk of developing CSA-AKI in routine clinical practice.

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Although postoperative acute kidney injury (AKI) is a serious complication after cardiac surgery, preventive measures are limited. Despite the known association of preoperative low magnesium levels with cardiac surgery-related atrial fibrillation, the association between preoperative magnesium concentration and postoperative AKI has not been fully elucidated. This study evaluated the association between preoperative serum magnesium level and the development of AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who underwent cardiac surgery at 2 South Korean tertiary hospitals between 2006 and 2020 were identified from medical records. Patients with missing information, an estimated glomerular filtration rate<15mL/min/1.73m2, receiving maintenance dialysis, or a history of AKI treated by dialysis within 1 year before surgery were excluded. EXPOSURE: Preoperative serum magnesium levels. OUTCOME: Postoperative AKI within 48 hours after surgery, defined using the Acute Kidney Injury Network (AKIN) criteria, and dialysis-treated AKI within 30 days after surgery. ANALYTICAL APPROACH: Multivariable logistic regression analysis. RESULTS: Among the 9,766 patients (median age, 64.0 years; 60.1% male), postoperative AKI and dialysis-treated AKI were observed in 40.1% and 4.3% patients, respectively. Postoperative AKI was more prevalent in patients with lower serum magnesium levels (44.9%, 41.4%, 39.4%, and 34.8% in quartiles 1-4, respectively). Multivariable logistic regression analysis revealed that the odds ratios (ORs) for postoperative AKI were progressively larger across progressively lower quartiles of serum magnesium concentration (adjusted ORs of 1.53 [95% CI, 1.33-1.76], 1.29 [95% CI, 1.12-1.48], 1.15 [95% CI, 1.01-1.31] for quartiles 1-3, respectively, relative to quartile 4, P for trend<0.001). Preoperative hypomagnesemia (serum magnesium level<1.09mg/dL) was also significantly associated with AKI (adjusted OR, 1.39 [95% CI, 1.10-1.77]) and dialysis-treated AKI (adjusted OR, 1.67 [95% CI, 1.02-2.72]). LIMITATIONS: Causality could not be evaluated in this observational study. CONCLUSIONS: Lower serum magnesium levels were associated with a higher incidence of AKI in patients undergoing cardiac surgery.

The Utility of Novel Kidney Injury Biomarkers in Early Detection of CSA-AKI.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common complications of cardiac surgery procedures. In this study, the authors attempt to provide new data regarding the application of novel kidney injury biomarkers in the early diagnostics of CSA-AKI. 128 adult patients undergoing elective cardiac surgery procedures with the use of cardiopulmonary by-pass (CPB) were enrolled in this study. Novel kidney injury biomarkers were marked in the plasma and urine 6 h after weaning from the CPB. A significant difference in the postoperative biomarkers' concentration between the AKI and no-AKI group was found, regarding plasma IL-8, plasma TNF-α and urine NGAL, normalized for creatinine excretion (NGAL/Cr). These were also independent predictors of CSA-AKI. An independent risk factor for CSA-AKI proved to be preoperative CKD. Plasma IL-8 and TNF-α, as well as urine NGAL/Cr, are independent early indicators of CSA-AKI and pose a promising alternative for creatinine measurements. The cut-off points for these biomarkers proposed in this investigation should be confronted with more data and revised to achieve a suitable diagnostic value.

Plasma microRNA-21 for the early prediction of acute kidney injury in patients undergoing major cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a complication after major cardiac surgery that is associated with higher rates of morbidity and mortality. MicroRNA-21 (miR-21) has been described as an early biomarker for AKI. We investigated whether miR-21 is predictive of AKI and long-term mortality after cardiac surgery. METHODS: Consecutive patients (n = 115) undergoing major cardiac surgery were included. Serum creatinine was measured prior to, 4 h after, and 1, 4 and 7 days after extracorporeal circulation. Diagnosis of post-operative AKI was made in accordance with the international Kidney Disease: Improving Global Outcomes definition of AKI. Serum cystatin C and miR-21 were measured prior to and 4 h after surgery. miR-21 was determined by quantitative RT-PCR and was normalized to miRNA-39 from Caenorhabditis elegans. The median follow-up time was 2.9 years. RESULTS: AKI occurred in 36.5% (n = 42) of all patients. Baseline miR-21 was significantly lower in patients developing cardiac surgery-associated AKI (CSA-AKI) than in patients without CSA-AKI [0.27 (interquartile range, IQR, 0.14-0.30) versus 0.44 (IQR 0.25-0.75); P < 0.01]. Baseline miR-21 predicted CSA-AKI Stage 2/3 with an area under the curve of 0.701 [95% confidence interval (CI) 0.59-0.82; P = 0.007]. Baseline miR-21 <0.31 showed a hazard ratio of 3.11 (95% CI: 1.33-11.26) for CSA-AKI Stage 2/3. Patients with AKI Stage 2/3 had a significantly higher mortality (50 versus 10%; P = 0.0001) and dialysis rate (27 versus 11%; P = 0.038) within the 2.9-year follow-up. CONCLUSIONS: Our results indicate that miR-21 has the potential to identify patients at higher risk for CSA-AKI. This predictive value might be helpful in pre-procedural risk assessment and peri-procedural diagnosis and treatment.

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 30 days, 60 days and 90 days. There is a significant interaction between patients with aged>65 years (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 60 days of CSA-AKI patients treated with ≥80 mg 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 ≥80 mg Atorvastatin may improve the prognosis of CSA-AKI.

A novel predictive model for poor in-hospital outcomes in patients with acute kidney injury after cardiac surgery.

OBJECTIVE: Patients with cardiac surgery-associated acute kidney injury are at risk of renal replacement therapy and in-hospital death. We aimed to develop and validate a novel predictive model for poor in-hospital outcomes among patients with cardiac surgery-associated acute kidney injury. METHODS: A total of 196 patients diagnosed with cardiac surgery-associated acute kidney injury were enrolled in this study as the training cohort, and 32 blood cytokines were measured. Least absolute shrinkage and selection operator regression and random forest quantile-classifier were performed to identify the key blood predictors for in-hospital composite outcomes (requiring renal replacement therapy or in-hospital death). The logistic regression model incorporating the selected predictors was validated internally using bootstrapping and externally in an independent cohort (n = 52). RESULTS: A change in serum creatinine (delta serum creatinine) and interleukin 16 and interleukin 8 were selected as key predictors for composite outcomes. The logistic regression model incorporating interleukin 16, interleukin 8, and delta serum creatinine yielded the optimal performance, with decent discrimination (area under the receiver operating characteristic curve: 0.947; area under the precision-recall curve: 0.809) and excellent calibration (Brier score: 0.056, Hosmer-Lemeshow test P = .651). Application of the model in the validation cohort yielded good discrimination. A nomogram was generated for clinical use, and decision curve analysis demonstrated that the new model adds more net benefit than delta serum creatinine. CONCLUSIONS: We developed and validated a promising predictive model for in-hospital composite outcomes among patients with cardiac surgery-associated acute kidney injury and demonstrated interleukin-16 and interleukin-8 as useful predictors to improve risk stratification for poor in-hospital outcomes among those with cardiac surgery-associated acute kidney injury.

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

BACKGROUND: Diabetic 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. METHODS: A 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. RESULTS: A 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). CONCLUSION: Elevated 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.

Assessment and Prognosis in CSA-AKI Using Novel Kidney Injury Biomarkers: A Prospective Observational Study.

BACKGROUND: There is a need for early diagnostic solutions for cardiac surgery associated acute kidney injury (CSA-AKI) as serum creatinine changes do not occur dynamically enough. Moreover, new approaches are needed for kidney protective strategy in patients undergoing cardiac surgery procedures; Methods: Samples of serum and urine were taken from the selected group of patients undergoing elective cardiac surgery procedures. The aim of this study was to assess the utility of specific inflammation and kidney injury biomarkers in the early diagnostic of CSA-AKI and in the prognosis of long-term postoperative kidney function; Results: At 6 h after weaning from cardiopulmonary bypass, there were significant differences in IL-6, IL-8, TNF-α, MMP-9 and NGAL concentrations in patients with CSA-AKI, compared to the control group. Serum IL-8 and urine NGAL 6 h after weaning from CPB proved to be independent acute kidney injury predictors. The TNF-α, MMP-9, IL-18, TIMP-1 and MMP-9/TIMP-1 ratio in the early postoperative period correlated with long-term kidney function impairment; Conclusions: Novel kidney injury biomarkers are an eligible tool for early diagnosis of CSA-AKI. They are also reliable indicators of long-term postoperative kidney function impairment risk after cardiac surgery procedures.

Novel Plasma Biomarker-Based Model for Predicting Acute Kidney Injury After Cardiac Surgery: A Case Control Study.

INTRODUCTION: Acute kidney injury (AKI) after cardiac surgery is independently associated with a prolonged hospital stay, increased cost of care, and increased post-operative mortality. Delayed elevation of serum creatinine (SCr) levels requires novel biomarkers to provide a prediction of AKI after cardiac surgery. Our objective was to find a novel blood biomarkers combination to construct a model for predicting AKI after cardiac surgery and risk stratification. METHODS: This was a case-control study. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to Gene Expression Omnibus (GEO) dataset GSE30718 to seek potential biomarkers associated with AKI. We measured biomarker levels in venous blood samples of 67 patients with AKI after cardiac surgery and 59 control patients in two cohorts. Clinical data were collected. We developed a multi-biomarker model for predicting cardiac-surgery-associated AKI and compared it with a traditional clinical-factor-based model. RESULTS: From bioinformatics analysis and previous articles, we found 6 potential plasma biomarkers for the prediction of AKI. Among them, 3 biomarkers, such as growth differentiation factor 15 (GDF15), soluble suppression of tumorigenicity 2 (ST2, IL1RL1), and soluble urokinase plasminogen activator receptor (uPAR) were found to have prediction ability for AKI (area under the curve [AUC] > 0.6) in patients undergoing cardiac surgery. They were then incorporated into a multi-biomarker model for predicting AKI (C-statistic: 0.84, Brier 0.15) which outperformed the traditional clinical-factor-based model (C-statistic: 0.73, Brier 0.16). CONCLUSION: Our research validated a promising plasma multi-biomarker model for predicting AKI after cardiac surgery.

Novel Blood Cytokine-Based Model for Predicting Severe Acute Kidney Injury and Poor Outcomes After Cardiac Surgery.

Background Alterations in serum creatinine levels delay the identification of severe cardiac surgery-associated acute kidney injury. To provide timely diagnosis, novel predictive tools should be investigated. Methods and Results This prospective observational study consists of a screening cohort (n=204) and a validation cohort (n=198) from 2 centers from our hospital. Thirty-two inflammatory cytokines were measured via a multiplex cytokine assay. Least absolute shrinkage and selection operator regression was conducted to select the cytokine signatures of severe cardiac surgery-associated acute kidney injury. Afterwards, the significant candidates including interferon-γ, interleukin-16, and MIP-1α (macrophage inflammatory protein-1 alpha) were integrated into the logistic regression model to construct a predictive model. The predictive accuracy of the model was evaluated in these 2 cohorts. The cytokine-based model yielded decent performance in both the screening (C-statistic: 0.87, Brier 0.10) and validation cohorts (C-statistic: 0.86, Brier 0.11). Decision curve analysis revealed that the cytokine-based model had a superior net benefit over both the clinical factor-based model and the established plasma biomarker-based model for predicting severe acute kidney injury. In addition, elevated concentrations of each cytokine were associated with longer mechanical ventilation times, intensive care unit stays, and hospital stays. They strongly predicted the risk of composite events (defined as treatment with renal replacement therapy and/or in-hospital death) (OR of the fourth versus the first quartile [95% CI]: interferon-γ, 27.78 [3.61-213.84], interleukin-16, 38.07 [4.98-291.07], and MIP-1α, 9.13 [2.84-29.33]). Conclusions Our study developed and validated a promising blood cytokine-based model for predicting severe acute kidney injury after cardiac surgery and identified prognostic biomarkers for assisting in outcome risk stratification.

Aspectos bioéticos en la seguridad del paciente tributario a cirugía cardiovascular y su protección renal: revisión sistemática / Bioethical aspects in the safety of cardiovascular surgery patients and their renal protection. Systematic review

La disfunción renal es frecuente y puede llegar a ser grave en los pacientes que requieren cirugía car-diaca. Existe actualmente un interés internacional creciente en las Unidades de Salud Seguras, que tienenpor finalidad generar un entorno de seguridad para el paciente quirúrgico. Dicho interés está basadotanto por el utilitarismo como por la defensa del gran valor que tiene la vida humana. El objetivo generaldel estudio fue analizar desde la bioética de los cuidados sanitarios y de los contenidos de la seguridaddel paciente, la lesión renal aguda asociada a cirugía cardiaca. Se realizó una revisión sistemática queempleó la metodología PRISMA en las bases de datos de PubMed con artículos publicados en los últimoscinco años. La fisiopatología de la entidad estudiada es compleja y aún poco conocida. En dicho periodo,prevaleció un gran interés por investigar la lesión renal aguda asociada a la cirugía cardiaca, sin embargo,no se encontraron otros estudios que abordara esta temática desde un enfoque bioético personalista. Seconstató alta calidad científica y rigor metodológico en los estudios incluidos, valorado por el predominiode revisiones sistemáticas, meta-análisis y estudios multicéntricos, randomizados, controlados doble ciego.En conclusión hemos iniciado en este trabajo un campo interesante y novedoso, incorporando perspecti-vas para una valoración integral y más humana, en la tomas de decisiones respecto la lesión renal agudaasociada a la cirugía cardiaca.(AU)

Renal dysfunction is common and can be severe in patients requiring cardiac surgery. There is currentlya growing international interest in the declaration of Safe Health Units, around the safety of the surgicalpatient. This interest is influenced at the same time by utilitarianism and the defense of the great valueof human life. The general objective was to analyze, from the bioethics of health care and the contents ofsurgical patient safety, acute kidney injury associated with cardiac surgery. A systematic review was carriedout using the PRISMA methodology in PubMed databases with articles published in the last five years. The pathophysiology of the entity studied is complex and still poorly understood. In this period, there was agreat interest in investigating acute kidney injury associated with cardiac surgery, however, no other stu-dies were found that addressed this issue from a personalist bioethical approach. High scientific qualityand methodological rigor were found in the included studies, assessed by the predominance of systematicreviews, meta-analyses, and multicenter, randomized, double-blind controlled studies. An interesting andnovel field is initiated, which facilitates, from perspectives with a comprehensive and more humane as-sessment, decision-making on acute kidney injury associated with cardiac surgery.(AU)