Aspirin use is associated with attenuated risk of severe acute kidney injury in septic patients: a dual-center retrospective analysis from MIMIC-IV and eICU cohorts

To explore the risk factors of severe acute kidney injury (AKI) in septic patients, and to establish an hour-specific prediction model. Based on the information of septic patients in the Medical Information Mart for Intensive Care- IV (MIMIC- IV) database, general information, comorbidities, vital signs, severity scoring system, laboratory indicators, invasive operations and medication use were recorded. The enrolled patients were randomized into a training set and a validation set according to a ratio of 7 : 3. AKI was diagnosed according to the guidelines of Kidney Disease: Improving Global Outcome (KDIGO). Based on Lasso regression and Cox regression, the risk factors of severe AKI (AKI stage 2 and stage 3) in septic patients were analyzed and hour-specific prediction model were established. Consistency index (C-index), area under the receiver operator characteristic curve (AUC) and calibration curve were used to assess the predictive efficacy of the model. A total of 20 551 septic patients were enrolled, including 14 385 patients in the training set and 6 166 patients in the validation set. Multivariate Cox regression analysis showed that atrial fibrillation [hazard ratio (HR) = 1.266, 95% confidence interval (95%CI) was 1.150-1.393], heart failure (HR = 1.348, 95%CI was 1.217-1.493), respiratory failure (HR = 1.565, 95%CI was 1.428-1.715), heart rate (HR = 1.004, 95%CI was 1.002-1.007), mean arterial pressure (HR = 1.245, 95%CI was 1.126-1.377), lactic acid (HR = 1.051, 95%CI was 1.025-1.077), simplified acute physiology score II (SAPS II, HR = 1.019, 95%CI was 1.016-1.023), serum creatinine (HR = 1.171, 95%CI was 1.127-1.216), anion gap (HR = 1.024, 95%CI was 1.010-1.038), serum potassium (HR = 1.155, 95%CI was 1.079-1.236), white blood cell count (HR = 1.006, 95%CI was 1.003-1.009) and furosemide use (HR = 0.414, 95%CI was 0.368-0.467) were independently associated with severe AKI in septic patients (all P < 0.01). The above predictors were applied to construct an hour-specific prediction model for the occurrence of severe AKI in septic patients. The C-index of the prediction model was 0.723 and 0.735 in the training and validation sets, respectively. The AUC for the occurrence of severe AKI at 12, 24, and 48 hours were 0.795 (95%CI was 0.782-0.808), 0.792 (95%CI was 0.780-0.805), and 0.775 (95%CI was 0.762-0.788) in the training set, and the AUC were 0.803 (95%CI was 0.784-0.823), 0.791 (95%CI was 0.772-0.810), and 0.773 (95%CI was 0.752-0.793) in the validation set, respectively. The calibration curves of the two cohorts were in good agreement. The hour-specific prediction model effectively identifies high-risk septic patients for developing severe AKI within 48 hours, aiding clinicians in stratifying patients for early therapeutic interventions to improve outcomes.

To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Perioperative Acute Kidney Injury

Sepsis-associated acute kidney injury is a common complication of sepsis, but it is difficult to predict sepsis-associated acute kidney injury. In this retrospective observational study, adult septic patients were recruited from the MIMIC-III database as the training cohort (n = 4764) and from Xiangya Hospital (n = 1568) and Zhang’s database as validation cohorts. We identified eleven predictors with seven independent risk predictors of sepsis-associated acute kidney injury [fluid input_day1 ≥ 3390 ml (HR hazard ratio 1.42), fluid input_day2 ≥ 2734 ml (HR 1.64), platelet_min_day5 ≤ 224.2 × 109/l (HR 0.86), length of ICU stay ≥ 2.5 days (HR 1.24), length of hospital stay ≥ 5.8 days (HR 1.18), Bun_max_day1 ≥ 20 mmol/l (HR 1.20), and mechanical ventilation time ≥ 96 h (HR 1.11)] by multivariate Cox regression analysis, and the eleven predictors were entered into the nomogram. The nomogram model showed a discriminative ability for estimating sepsis-associated acute kidney injury. These results indicated that clinical parameters such as excess input fluid on the first and second days after admission and longer mechanical ventilation time could increase the risk of developing sepsis-associated acute kidney injury. With our study, we built a real-time prediction model for potentially forecasting acute kidney injury in septic patients that can help clinicians make decisions as early as possible to avoid sepsis-associated acute kidney injury.

Background &amp; objective: Sepsis is a medical emergency that requires quick and adequate treatment. In various epidemiological studies it is said that 11–60 % of sepsis patients may suffer from acute kidney injury (AKI). The incidence is 23% in the severe sepsis and 51–64 % in septic shock patients. A number of studies reported that a high value of central venous pressure (CVP) is associated with high incidence and morbidity of AKI in sepsis. We conducted this study to compare a cutoff point of 8 mmHg of CVP with the incidence of AKI in sepsis patients admitted in ICU. Methodology: This study is an observational analytical cohort prospective study. The sampling was done by consecutive sampling technique. Patients were assigned into 2 groups with each group consisting of 41 samples. CVP measurement was done manually. AKI were assessed by measuring the serum creatinine twice and examining the patient's urine. To analyze the relationship between CVP and the frequency of AKI, chi-square test was performed. Results: Of the 41 subjects with CVP ≥ 8 mmHg, 29 of them (60.4%) were diagnosed with AKI. Chi-square test revealed a significant correlation between target CVP and AKI incidence (p = 0.025). Also, age, sex, norepinephrine use and type of infection did not correlate with AKI incidence (p &gt; 0.05). The only factor related to AKI significantly was CVP with RR 1.526 (95% CI: 1.04-2.24) and p-value of 0.025 Conclusion: In conclusion, a CVP target value of 8 mmHg or higher has a higher risk of AKI. The use of fluid therapy in managing sepsis requires strict fluid monitoring and evaluation. Key words: Acute kidney injury; AKI, Central venous pressure; Fluid therapy; sepsis Citation: Sucipto A, Permana SA. Correlation between central venous pressure and acute kidney injury in septic patients. Anaesth. pain intensive care 2021;25(5):638–642; DOI: 10.35975/apic.v25i5.1632 Received: March 05, 2021, Reviewed: June 14, 2021, Accepted: June 15, 2021

Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients. We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital. 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825-0.921) and 0.826 (95% CI 0.727-0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value. The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.

Pretransplant Predictors and Posttransplant Sequels of Acute Kidney Injury after Allogeneic Stem Cell Transplantation

Acute Kidney Injury

1. David T. Selewski, MD* 2. Jordan M. Symons, MD† 1. *Department of Pediatrics and Communicable Diseases, Division of Nephrology, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI. 2. †Department of Pediatrics, Division of Nephrology, University of Washington School of Medicine, Seattle, WA. * Abbreviations: ACE: : angiotensin-converting enzyme AKI: : acute kidney injury AKIN: : Acute Kidney Injury Network ANCA: : antineutrophil cytoplasmic antibody ATN: : acute tubular necrosis ECG: : electrocardiogram FEurea: : fractional excretion of urea FENa: : fractional excretion of sodium KDIGO: : Kidney Disease: Improving Global Outcomes NSAID: : nonsteroidal anti-inflammatory drug RIFLE: : Risk, Injury, Failure, Loss, and End-stage The term acute kidney injury has replaced acute renal failure and represents a spectrum of clinically meaningful kidney damage. After completing this article, readers should be able to: 1. Recognize and define the spectrum of acute kidney injury (AKI). 2. Understand the diagnostic approach and be able to differentiate the main causes of AKI. 3. Understand the complications of AKI and the treatment of a child with AKI. Acute kidney injury (AKI), formerly called acute renal failure, is characterized by multiple abnormalities, including increases in serum creatinine and blood urea nitrogen, electrolyte abnormalities, acidosis, and difficulties with fluid management. We have come to realize that what was previously thought to be relatively minor damage to the kidney can have significant short-term effects on morbidity and mortality and potential long-term implications for the development of chronic kidney disease. Thus, the term acute kidney injury has replaced acute renal failure , suggesting the spectrum of kidney damage that can occur. ### Definition AKI is classically defined as an acute decrease in glomerular filtration rate, which results in an increase in serum creatinine. It is important to recognize the limitations of creatinine as a marker of AKI because an increase in creatinine can be delayed by as much as 48 hours after damage to the kidney has occurred. Despite this limitation, change in creatinine remains the gold standard for the diagnosis of AKI. An evolution in the definition of AKI to better understand, characterize, and study the disease spectrum, has occurred, which has sought to capture the clinical importance of even small variations in kidney function. In addition, previous definitions used in the literature were widely disparate; this …

Acute kidney injury (AKI) is frequently caused by sepsis. Recently, the Acute Disease Quality Initiative (ADQI) workgroup further classified AKI as transient or persistent. Oliguria and increased serum creatinine represent two different kinds of renal impairment. The aim of the study was to assess mortality and cumulative AKI score associated with transient and persistent AKI in septic patients. Septic patients were stratified according to the presence and AKI development (considered persistent when remaining >48 h) were included. An adjusted logistic regression model was used to determine hospital mortality. In addition, we calculated an AKI score by combining both Kidney Disease: Improving Global Outcomes (KDIGO) criteria of urine output and creatinine AKI stages. The relationship between the cumulative AKI score and persistent AKI was further examined using the logistic regression model and receiver operating characteristic (ROC) curve analysis. 12928 septic patients were enrolled in the study. AKI occurred in 73.7% of septic patients, in 39.5% was transient and in 60.5% was persistent. Patients with persistent AKI had higher severity scores and more severe renal dysfunction upon admission. Persistent AKI, but not transient AKI, was associated with increased intensive care units (ICUs) and hospital mortality. Then we found that the cumulative AKI score was associated with an increased risk of persistent AKI. This association was consistent across three original KDIGO severity stages and subgroup analyses. It was found that persistent AKI was independently associated with mortality in septic patients. Furthermore, serum creatinine and urine output criteria had cumulative effects on KDIGO AKI staging and provided more information about the relationship between AKI and outcomes.

Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients' quality of life. We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients' baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3. A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4%), 73 (13.2%), and 229 (41.4%) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2% vs 26.0% or 22.7%; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery: 65.1% vs 27.4% or 22.7%; P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95% CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95% CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate >20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups. The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.

Case Scenario: Hemodynamic Management of Postoperative Acute Kidney Injury

Hypotension during liver transplantation often requires vasopressor therapy. Acute kidney injury is a common complication after liver transplantation. Vasopressin acts as a portal flow modulator, may increase the glomerular filtration rate, and reduce the dose of catecholamines required. We hypothesized that intraoperative vasopressin use could be associated with reduced postoperative acute kidney injury. This single-center retrospective cohort study included 1120 adult liver transplant recipients between June 2012 and November 2022. We assessed the association between intraoperative vasopressin use and postoperative severe acute kidney injury by using a propensity score-adjusted multivariable regression model. The incidence of severe postoperative acute kidney injury was 29.2%. The median age was 60 y, 64.9% of patients were males. Vasopressin was used in 34.0% of the cases. Patients receiving vasopressin had a higher Model for End-Stage Liver Disease-sodium score (24 versus 16, P < 0.001). The median [interquartile range] dose of catecholamine vasopressors was significantly higher in patients who received vasopressin (0.08 [0.05-0.12] versus 0.03 [0.01-0.05] µg·kg-1·min-1 norepinephrine equivalents, P < 0.001). We did not observe an association between the intraoperative use of vasopressin and severe acute kidney injury after liver transplantation (adjusted odds ratio: 1.29; 95% confidence interval: 0.92-1.80). Vasopressin use was not associated with a higher hazard of experiencing graft failure or related outcomes over time (hazard ratio = 1.17, P = 0.44). In patients requiring high doses of intraoperative vasopressors during liver transplantation, vasopressin use was not associated with an increased risk of severe postoperative acute kidney injury or decreased graft survival.

The TyG index serves as a valuable tool for evaluating insulin resistance. An elevated TyG has shown a strong association with the occurrence of acute kidney injury (AKI). Nevertheless, existing literature does not address the relationship between the TyG index and acute kidney injury in patients with sepsis. Sepsis patients were identified from the MIMIC-IV database and categorized into four groups according to quadrilles of their TyG index values. The primary outcome of this study was the incidence of AKI. The relationship between the TyG index and the risk of AKI in septic patients was evaluated using Cox proportional hazards and restricted cubic spline models. Subgroup analyses were conducted to investigate the prognostic value of the TyG index in different subgroups. A total of 2,616 patients with sepsis (57% of whom were male) were included in this study. The incidence of AKI was found to be 78%. Cox proportional hazards analysis revealed a significant correlation between the TyG index and the occurrence of AKI in septic patients. Furthermore, a restricted cubic spline model revealed an approximately linear relationship between a higher TyG index and an elevated risk of AKI in septic patients. The trend of the hazard ratio (HR) remained consistent across various subgroups. These findings emphasize the reliability of the TyG index as an independent predictor for the occurrence of AKI and unfavorable renal outcomes in sepsis patients. Nevertheless, establishing a causal relationship between the two requires demonstration through larger prospective studies.