Diagnosis Of Acute Kidney Injury Research Articles

Biomarkers vs Machines: The Race to Predict Acute Kidney Injury.

Acute kidney injury (AKI) is a serious complication affecting up to 15% of hospitalized patients. Early diagnosis is critical to prevent irreversible kidney damage that could otherwise lead to significant morbidity and mortality. However, AKI is a clinically silent syndrome, and current detection primarily relies on measuring a rise in serum creatinine, an imperfect marker that can be slow to react to developing AKI. Over the past decade, new innovations have emerged in the form of biomarkers and artificial intelligence tools to aid in the early diagnosis and prediction of imminent AKI. This review summarizes and critically evaluates the latest developments in AKI detection and prediction by emerging biomarkers and artificial intelligence. Main guidelines and studies discussed herein include those evaluating clinical utilitiy of alternate filtration markers such as cystatin C and structural injury markers such as neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloprotease 2 with insulin-like growth factor binding protein 7 and machine learning algorithms for the detection and prediction of AKI in adult and pediatric populations. Recommendations for clinical practices considering the adoption of these new tools are also provided. The race to detect AKI is heating up. Regulatory approval of select biomarkers for clinical use and the emergence of machine learning algorithms that can predict imminent AKI with high accuracy are all promising developments. But the race is far from being won. Future research focusing on clinical outcome studies that demonstrate the utility and validity of implementing these new tools into clinical practice is needed.

635 - Impact of race on renal recovery in patients with new diagnosis of multiple myeloma and acute kidney injury requiring dialysis

635 - Impact of race on renal recovery in patients with new diagnosis of multiple myeloma and acute kidney injury requiring dialysis

Early diagnosis of acute kidney injury in children with poisoning of chemical etiology

Purpose. The study aims at optimizing the diagnosis of acute kidney injury in children with poisoning of chemical etiology based on the use of early markers of kidney damage.Materials and Methods. The study enrolled 120 patients aged 1–18 years with poisoning of chemical etiology. Routine methods of kidney function estimation were supplemented by an investigation of urinary concentration of acute kidney injury early markers: lipocalin-2, kidney injury molecule-1. All children were hospitalized in a toxicology unit on the 1st day after exposure to toxic substance. Twenty practically healthy children aged 1–18 years were examined as control group.Results. Only one patient (0.8%) had acute kidney injury determined as increased serum creatinine at the time of admission, but at the same time 35 children (29.2%) had increased levels of one or more urinary markers. By the 3rd day 32 of those 35 children with increased urinary markers developed acute kidney injury stages 1 or 2, determined as significant rise of serum creatinine and decrease of renal blood flow according to Doppler ultrasound. On the contrary, no patient with initially normal level of urinary markers developed acute kidney injury. Thus, 32/120 patients hospitalized with poisoning of chemical etiology, developed acute kidney injury (26.7%).Conclusion. Increased urinary excretion of lipocalin-2 and kidney injury molecule-1 at the first day of acute chemical poisoning can be estimated as predictive marker of acute kidney injury development.

Kidney Disease Awareness and Knowledge Among Families and Pediatric Survivors of Severe Acute Kidney In

Background: Acute kidney injury (AKI) is common in pediatric patients and is associated with poor outcomes including increased risk of chronic kidney disease. It is unknown whether pediatric AKI survivors and their families are aware of their AKI diagnosis and understand the associated risks. We are seeking to identify awareness and disease-specific knowledge among pediatric AKI survivors and their families.
 Objectives: We hypothesize that pediatric AKI survivors and their families have a low awareness of their diagnosis and want more information about kidney health.
 Design/Methods: We performed a cross-sectional survey of AKI awareness and knowledge in pediatric patients with KDIGO Stage II or III AKI and their families near the time of discharge from Riley Hospital for Children. Families answered questions on AKI diagnosis awareness and AKI knowledge using the Kidney Knowledge Survey (KiKS).
 Results: Of 16 families included in this analysis, 75% were unaware they had experienced AKI and 94% were unaware they had a ‘problem with their kidneys’. Overall, the median AKI objective knowledge score was 60% (IQR: 31%, 69%). There was no difference in knowledge score between those that recognized their episode of AKI and those that did not. In total, 69% of families correctly defined AKI as when ‘your kidneys suddenly stop working well’. Most families recognized dehydration (56%) and infection (81%) as risk factors for AKI, however fewer recognized other risk factors such as ibuprofen use (31%). Only 38% of families reported that someone had discussed AKI during their admission, and 88% stated they wanted to learn more about AKI.
 Conclusion: Most families of pediatric survivors of severe AKI were unaware that their child had AKI or problems with their kidneys. Many lacked understanding of AKI risk factors and knowledge of kidney health and desired more information.

Machine-learning model for predicting oliguria in critically ill patients

This retrospective cohort study aimed to develop and evaluate a machine-learning algorithm for predicting oliguria, a sign of acute kidney injury (AKI). To this end, electronic health record data from consecutive patients admitted to the intensive care unit (ICU) between 2010 and 2019 were used and oliguria was defined as a urine output of less than 0.5 mL/kg/h. Furthermore, a light-gradient boosting machine was used for model development. Among the 9,241 patients who participated in the study, the proportions of patients with urine output < 0.5 mL/kg/h for 6 h and with AKI during the ICU stay were 27.4% and 30.2%, respectively. The area under the curve (AUC) values provided by the prediction algorithm for the onset of oliguria at 6 h and 72 h using 28 clinically relevant variables were 0.964 (a 95% confidence interval (CI) of 0.963–0.965) and 0.916 (a 95% CI of 0.914–0.918), respectively. The Shapley additive explanation analysis for predicting oliguria at 6 h identified urine values, severity scores, serum creatinine, oxygen partial pressure, fibrinogen/fibrin degradation products, interleukin-6, and peripheral temperature as important variables. Thus, this study demonstrates that a machine-learning algorithm can accurately predict oliguria onset in ICU patients, suggesting the importance of oliguria in the early diagnosis and optimal management of AKI.

Shear wave elastography: A noninvasive approach for assessing acute kidney injury in critically ill patients.

Traditional markers, such as serum creatinine and blood urea nitrogen, frequently show delayed elevations following acute kidney injury (AKI), limiting their utility for prompt detection and timely intervention in AKI management. Shear wave elastography (SWE) exhibits potential for AKI diagnosis by measuring tissue stiffness. Our study aimed to evaluate the diagnostic performance of SWE in detecting AKI by measuring the stiffness of kidney tissue. Between July 2022 and December 2022, a total of 103 consecutive participants who met the eligibility criteria were prospectively enrolled, underwent SWE measurements, and were classified into AKI or non-AKI groups based on the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A receiver operating characteristic (ROC) curve was drawn to examine the feasibility of differentiating between AKI and non-AKI patients and assessing diagnostic performance. The effects of tissue anisotropy on SWE measurements were also examined. Our results revealed that patients in the AKI group exhibited significantly increased stiffness values in specific kidney regions compared with those in the non-AKI group. For the diagnosis of AKI, the optimal cut-off values were identified as 9.9 kPa, 2.9 kPa, and 4.4 kPa for the upper pole medulla, middle cortex, and middle medulla, respectively, in the longitudinal plane. Correspondingly, the areas under the ROC curves for these regions were 0.737 (95% confidence interval [CI]: 0.637, 0.822), 0.736 (95% CI: 0.637, 0.821), and 0.784 (95% CI: 0.688, 0.861). Additionally, we observed a significant variability in stiffness values due to tissue anisotropy, specifically in the segments of the upper pole cortex, and medulla across both longitudinal and transverse planes. SWE serves as a noninvasive approach for the quantification of tissue stiffness and shows promise as an adjunctive tool for the assessment of AKI.

Toward Precision Medicine: Exploring the Landscape of Biomarkers in Acute Kidney Injury.

Acute kidney injury (AKI) remains a complex challenge with diverse underlying pathological mechanisms and etiologies. Current detection methods predominantly rely on serum creatinine, which exhibits substantial limitations in specificity and poses the issue of late-stage detection of kidney injury. In this review, we propose an up-to-date and comprehensive summary of advancements that identified novel biomarker candidates in blood and urine and ideal criteria for AKI biomarkers such as renal injury specificity, mechanistic insight, prognostic capacity, and affordability. Recently identified biomarkers not only indicate injury location but also offer valuable insights into a range of pathological processes, encompassing reduced glomerular filtration rate, tubular function, inflammation, and adaptive response to injury. The clinical applications of AKI biomarkers are becoming extensive and serving as relevant tools in distinguishing acute tubular necrosis from other acute renal conditions. Also, these biomarkers can offer significant insights into the risk of progression to chronic kidney disease CKD and in the context of kidney transplantation. Integration of these biomarkers into clinical practice has the potential to improve early diagnosis of AKI and revolutionize the design of clinical trials, offering valuable endpoints for therapeutic interventions and enhancing patient care and outcomes.

Effects of diethylene glycol contamination of pharmaceutical products on unexplained acute kidney injury in children: a systematic review.

Unexplained acute kidney injury (AKI) in children owing to diethylene glycol (DEG) contamination during drug production has gained attention in recent years. This qualitative study investigated the effects of DEG exposure on the incidence of unknown AKI in children. A systematic review following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines was proposed to search for studies using predefined search terms in the PubMed, EBSCO, and Web of Science databases without publication date restrictions. The inclusion criteria are observational study, case study, case report, and case series design; and having provided accurate data for DEG poisoning and AKI diagnosis in children. All authors performed the study screening, data extraction, and data synthesis processes. Consensus was reached by mutual agreement. The data synthesis was conducted according to the DEG and unexplained AKI in children by examining the statistical data using Microsoft Excel 2017 and storing the data using the cloud service of Universitas Islam Indonesia. Of the 115 included studies, 21 met the inclusion criteria, including 2 case-control studies, 1 cross-sectional study, 4 case studies, and 14 case reports. DEG-contaminated paracetamol caused unexplained AKI in children. Other drugs including cough expectorants, antihistamines, and sedatives were administered. Chemicals other than DEG, such as propylene glycol and ethylene glycol, also induce AKI owing to overprescription and unintentional exposure. A recent epidemic of unexplained AKI showed contaminated paracetamol as the poisoning agent regardless of formula.

Risk factors of acute kidney injury during hospitalization in acute ischaemic stroke patients undergoing mechanical thrombectomy.

Acute kidney injury (AKI) seems to worsen the prognosis of acute ischaemic stroke (AIS) patients treated with mechanical thrombectomy (MT). At the same time, the procedure of MT increases AKI risk by iodinated contrast use. Identification of factors predisposing to AKI after MT is important for recognizing vulnerable patients and successful prevention. To identify factors associated with the occurrence of AKI during hospitalization in MT-treated AIS patients. The study included all AIS patients treated with MT in the University Hospital in Krakow from 2019 to 2021. The diagnosis of AKI during hospitalisation was based on serum creatinine concentration levels, according to the Kidney Disease Improving Global Outcomes guidelines. We compared patients with and without AKI in terms of age, sex, comorbidities, stroke course and laboratory test results at admission. We identified factors associated with the occurrence of AKI using univariate logistic regression analysis, with significant variables subsequently added to the multivariate analyses. Among 593 MT-treated AIS patients the incidence of AKI during hospitalisation was 12.6%. AKI development was associated with diabetes, chronic kidney disease, total volume of iodinated contrast obtained during hospitalisation, posterior circulation stroke, lack of intravenous thrombolysis, and laboratory test results at admission: haemoglobin, glucose, urea, potassium, and creatinine. Total contrast volume and urea level were the most important independent risk factors associated with occurrence of AKI. AKI is common in MT-treated AIS patients. There is a need to establish a protocol for decreasing the risk of AKI in AIS patients undergoing MT and, in case it occurs, a procedure for its treatment.

The Role of urinary kidney injury molecule 1 (KIM-1) in monitoring the treatment response in Egyptian Lupus Nephritis Patients

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to permanent renal damage. Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary kidney injury molecule-1 (UKIM-1) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. This study intended to determine the predictive performance of UKIM-1 among LN patients in response to induction therapy by assessing and correlating its levels with renal disease activity. The study included 60 SLE patients divided into 20 SLE patients with active lupus nephritis, 20 SLE patients with inactive lupus nephritis, and 20 lupus patients without nephritis as controls. The study was completed after six months from induction treatment. UKIM-1 was measured by an enzyme linked immunosorbent assay at baseline, three-month follow-up and after complete induction therapy. At baseline, the mean serum creatinine and mean UKIM-1 were 1.7 ±0.7 mg/dL and 10.3 ±1.2 ng/dL, respectively in active LN patients. The mean UKIM-1 levels of complete response and partial response groups were 9.8 ±0.9 ng/mL and 11.3 ±1.0 ng/mL respectively. Based on receiver operating characteristics curve analysis, we found a better diagnostic performance of UKIM-1 to predict response to induction treatment, outperforming conventional biomarkers. The sensitivity and specificity were 84.6% and 85.7 %, respectively at an area under the curve of 0.896 and the best cut-off level was ≤10.6 ng/mL. In conclusion, UKIM-1 performed better than conventional biomarkers in predicting response to treatment of active LN.

Review of the limitations of current biomarkers in acute kidney injury clinical practices.

Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging. Hence, the current guidelines are still developing to improve and understand the clinical implications of risk factors and earlier predictive biomarkers of acute kidney injury. Yet, studies have indicated disadvantages and limitations with the current acute kidney injury biomarkers, including lack of sensitivity and specificity. Therefore, the present narrative review brings together the most current evidenced-based practice and literature associated with the limitations of the gold standard for acute kidney injury diagnoses, the need for novel acute kidney injury biomarkers, and the process for biomarkers to be qualified for diagnostic use under the following sections and themes. The introduction section situates the anatomy and normal and abnormal kidney functions related to acute kidney injury disorders. Guidelines in providing acute kidney injury definitions and classification are then considered, followed by a discussion of the disadvantages of standard markers used to diagnose acute kidney injury. Characteristics of an ideal acute kidney injury biomarker are discussed concerning sensitivity, specificity, and anatomic location of injury. A particular focus on the role and function of emerging biomarkers is discussed in relation to their applications and significance to the prognosis and severity of acute kidney injury. Findings show emerging markers are early indicators of acute kidney injury prediction in different clinical settings. Finally, the process required for a biomarker to be applied for diagnostic use is explained.

Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

Acute kidney injury (AKI) is common in hospitalized patients with cirrhosis. Hepatorenal syndrome (HRS) is a type of AKI known as HRS-AKI. It is a severe complication of cirrhosis with high morbidity and mortality. While certain vasoconstrictor medications have been shown to improve HRS-AKI, no clear transplant-free survival benefit has been reported with medical therapies. Patients with HRS-AKI should be considered for urgent liver transplantation evaluation. In this review, we discuss the most recent updates on the definition, diagnosis, and management of AKI in cirrhosis, with special a emphasis on HRS.

The Utility of Urinary NGAL as an Alternative for Serum Creatinine to Detect Acute Kidney Injury in Infants Exposed to Nephrotoxic Medications in the Neonatal Intensive Care Unit

Introduction: Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program. Methods: This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to 7 days of NTM exposure plus 2 days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs. Results: The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3–100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39–4.13). Discussion/Conclusion: We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.

Serum total protein-to-albumin ratio predicts risk of death in septic acute kidney injury patients: A cohort study

ObjectiveSepsis is the leading cause of acute kidney injury (AKI). Increasing evidence shows that serum total protein-to-albumin ratio (TAR) could serve as an inflammation- and nutrition-based prognostic marker in various diseases. The purpose of this study was to assess the prognostic value of TAR in predicting the clinical outcomes of septic AKI patients. MethodsWe retrospectively enrolled septic AKI patients between August 2015 and August 2022 at West China Hospital of Sichuan University. Patients admitted between August 2015 and August 2021 were defined as the original cohort. The primary outcomes were 30-day and 90-day all-cause mortality of septic AKI patients. The secondary outcomes were septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, and stage 3 AKI. The utility of TAR was further verified in a validation cohort of septic AKI patients admitted between September 2021 and August 2022. ResultsIn the original cohort, a total of 309 eligible patients with a median age of 58 years were enrolled, of which 70.2 % were males. In multivariate Cox analysis, after adjustments for age, sex, and other confounding factors, higher TAR at admission was associated with an increased risk of 30-day and 90-day all-cause mortality in septic AKI patients (HR 1.91, 95 % CI 1.18–3.09, P = 0.008; HR 1.54, 95 % CI 1.01–2.34, P = 0.043, respectively). Subgroup analysis revealed no significant interactions in most strata. TAR at AKI diagnosis or discharge was not significantly related to 30-day (P = 0.120 and 0.153, respectively) or 90-day mortality (P = 0.147 and 0.124, respectively). We found no relationship between baseline TAR and septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, or stage 3 AKI (all P > 0.05). In the validation cohort of 81 septic AKI patients, TAR at admission remained a significant prognosticator for 30-day and 90-day mortality (HR 4.367, 95 % CI 1.20–15.87, P = 0.025; HR 4.237, 95 % CI 1.59–11.27, P = 0.004). ConclusionsTAR at admission is an independent risk factor for 30-day and 90-day mortality in septic AKI patients and could be used as a convenient and economic septic AKI prognostic indicator.

The problem of the diagnosis of acute kidney injury in children operated under the conditions of artificial circulation

Acute kidney injury (AKI) associated with cardiac surgery in children is one of the most frequent complications of the postoperative period appearing due to various perioperative factors. Generally accepted criteria for the diagnosis of AKI, on the one hand, may underestimate the frequency of development of this complication, on the other hand, require verification for use in the pediatric population. The application of kidney injury markers in pediatric practice is associated with a number of difficulties. For example, the high variability of the concentration of markers depending on age complicates the interpretation of the result, and maternal molecules can circulate in the blood of newborns. At the same time, in the cardiac surgery practice, the greatest impact of the measurement of kidney injury markers in children has been noted, which allows significantly accelerate the diagnosis of this complication and the starting of its therapy.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study—protocol for a phase 3, randomized, controlled trial

BackgroundRed blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies.MethodsReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%.DiscussionRBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

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.

Risk factors and fetomaternal outcome in pregnancy-related acute kidney injury.

Pregnancy-related acute kidney injury (PRAKI) is acute kidney injury (AKI) occurring during pregnancy, labor, and postpartum period. AKI is defined as suddenly impaired kidney function with the retention of nitrogenous and other waste products. In high population country like India, not all deliveries are done tertiary care. Even not all are registered one if delivery is conducted at a hospital setup. The majority of patients are being managed by available obstetrician at local places. Early diagnosis and timely management of complications related to pregnancy are very important to avoid PRAKI. We aim to study maternal risk factors and fetomaternal outcome in PRAKI. A prospective study is conducted between 2021 and 2022 in the Department of Obstetrics and Gynaecology, VMMC, and Safdarjung Hospital, New Delhi. For antenatal and delivered women up to 6 weeks, 50 patients were recruited according to KDIGO (Kidney Disease International Global Outcomes) criteria. Patients were followed with CBC, serum electrolytes, serial KFT, urine input/output monitoring, and USG-KUB. Dialysis was done if indicated. Complete renal recovery was considered if S.Cr ≤1.0 mg/dl within 6 weeks of diagnosis of AKI. For statistical significance, a P value of less than 0.05 was considered. The majority of patients were unbooked, 21-25 years of age, and belonged to lower socioeconomic status (54%). Risk factors were: preeclampsia (28%), puerperal sepsis (24%), PPH (20%), abruption (14%), pyelonephritis (4%), acute gastroenteritis (4%), gestational hypertension with superimposed preeclampsia (2%), antepartum eclampsia (2%), and thrombotic microangiopathy (2%). Hemodialysis is required in 23 (46%). Complete renal recovery was seen in 40 (80%) and partial renal recovery in 3 (6%). Maternal mortality was 14% and causes were: puerperal sepsis (57%), preeclampsia with severe features with MODS (29%), and antepartum eclampsia with hepatorenal failure (14%). Fetal outcome: 76% live birth, 24% intrauterine death, and 16% early neonatal death. Most common risk factors for PRAKI are preeclampsia followed by puerperal sepsis and PPH where all are preventable causes.

Disseminated intravascular coagulation is strongly associated with severe acute kidney injury in patients with septic shock

BackgroundDisseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute kidney injury (AKI) occurrence, severity, and evolution in this setting are available. We aimed at analyzing the association between AKI occurrence, severity and evolution in patients with septic shock-induced DIC. In a prospective monocentric cohort study, consecutive patients, 18 years and older, admitted in the ICU of Strasbourg University Hospital in the setting of systemic hypotension requiring vasopressor related to an infection, without history of terminal chronic kidney disease were eligible. AKI was defined according to the KDIGO classification. DIC diagnosis was based on the International Society on Thrombosis and Haemostasis (ISTH) score. Evolution of AKI was evaluated through the composite endpoint of major adverse kidney events. Only patients with DIC that occurred before or at the time of AKI diagnosis were considered. Univariate and multivariate analysis were performed to determine factors associated with renal outcomes.Results350 patients were included, of whom 129 experienced DIC. Patients with DIC were more seriously ill (median SAPS II 64 vs. 56, p < 0.001), and had higher 28-day mortality (43.3% vs. 26.2%, p < 0.001). AKI was more frequent in patients with DIC (86.8% vs. 74.2%, p < 0.005), particularly for the more severe stage of AKI [KDIGO 3 in 58.1% of patients with DIC vs. 30.8% of patients without DIC, p < 0.001, AKI requiring renal replacement therapy (RRT) in 47.3% of patients with DIC vs. 21.3% of patients without DIC, p < 0.001]. After adjustment for confounding factors, DIC occurrence remained associated with the risk of having the more severe stage of AKI with an odds ratio (OR) of 2.74 [IC 95% (1.53–4.91), p < 0.001], and with the risk of requiring RRT during the ICU stay [OR 2.82 (1.53–5.2), p < 0.001].ConclusionDIC appears to be strongly associated with the risk of developing the more severe form of AKI (stage 3 of the KDIGO classification, RRT requirement), even after adjustment for severity and other relevant factors.

Global biomarkers trends in acute kidney injury: a bibliometric analysis

Objectives Acute kidney injury (AKI) is a common global condition with high morbidity and mortality rates. Biomarkers can aid in the diagnosis, prediction, intervention, and outcome assessment of AKI. This study aimed to summarize the current research status and identify research hotspots for AKI biomarkers using bibliometric analysis. Methods Relevant original English language articles were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection database, from inception to 31 December 2022. Full records and related cited references from all the documents were collected and analyzed. Results A total of 16368 authors from 3379 institutions in 83 countries/regions contributed to 2916 documents that were published in 712 academic journals. Annual publication output followed exponential growth since 2008. The United States, the University of Pittsburgh, and the American Journal of Physiology-Renal Physiology were the most productive countries, institutions, and journals in terms of research outputs, respectively. The area of interest has shifted from neutrophil gelatinase-associated lipocalin, cell cycle, and tubular damage toward sepsis and COVID-19. Apoptosis, inflammation, and chronic kidney disease have become popular in recent years, and studies on ferroptosis, machine learning, COVID-19, and renal fibrosis will be the focus of future research. Implications This bibliometric study suggests that future research on AKI biomarkers would focus on ferroptosis, renal fibrosis and COVID-19. Artificial intelligence, such as machine learning, maybe the most promising direction for the discovery and validation of AKI biomarkers.