Reduction In Acute Kidney Injury Research Articles

P-1761. Safety and Efficacy of Antimicrobial Optimization based on Negative Results from BioFire FilmArray Pneumonia Panel

Abstract Background The BioFire FilmArray Pneumonia (BFP) panel is a multiplexed nucleic acid test intended for detection of multiple respiratory viral and bacterial specimens from sputum or bronchoalveolar lavage (BAL) specimens, with high specificity and turnaround time. Efficacy and safety of de-escalation strategies in patients with negative BFP have not been adequately described. Methods This was a multi-center, retrospective analysis of adult patients with suspected pneumonia and sputum or BAL samples that tested negative on BFP. Patients for whom antibiotic therapy was discontinued (ATDC Group) were compared to patients who had their antibiotic therapy continued (ATC Group). Outcomes included in-hospital mortality, 30-day readmission, and hospital and ICU length of stay. Impact on the total number of days on antibiotics and the safety of the intervention were also assessed. Results Out of 500 patients with negative BFP assay, a total of 185 patients were included in the final analysis (59 ATDC Group vs. 126 ATC Group). 67.6% of samples were sputum and 32.4% were BAL in the entire cohort. The groups were generally well-balanced in baseline characteristics, but more patients in ATC Group had community-acquired pneumonia (59% vs 79%, p = 0.006), higher initial white blood cell count (10 vs 13, p = 0.038), and higher quick Pitt Bacteremia Score (1 [IQR 0-1] vs 1 [IQR 0-3], p = 0.020). The ATDC Group had significantly shorter days of total antibiotic therapy (1.0 days vs 10.6 days, p < 0.001). 30-day readmission rates (16.95% vs 15.87%, p = 0.853) and the hospital length of stay (8.34 days vs 7.75, p = 0.960) did not differ. The ATDC Group experienced fewer AKI (8% vs 37%, p = 0.004). Duration of Antibiotics Conclusion Antibiotic discontinuation based on BFP was associated with significant reduction in the number of total days on antibiotics. Discontinuation was not associated with increases in in-hospital mortality, length of stay, or readmission, but was associated with a significant reduction in acute kidney injury. Disclosures All Authors: No reported disclosures

Reduction of vancomycin-associated acute kidney injury with montelukast.

Vancomycin ranks amongst the most utilized antimicrobial agents in the treatment of serious β-lactam-resistant Gram-positive infections, but its use has been associated with nephrotoxicity. Reduction of acute kidney injury (AKI) has been reported in pre-clinical models with adjuvant montelukast. The purpose of the study was to ascertain if montelukast was associated with a reduction in the prevalence of vancomycin-associated AKI. In this retrospective cohort study, adult patients who received intravenous vancomycin between January 2020 to January 2024 were examined. The RIFLE criteria was employed in identifying cases of AKI. Additionally, a pre-clinical vancomycin-associated nephrotoxicity model was established to provide insights into possible renal protective mechanisms. Patients receiving montelukast (n = 110) were compared to the control (n = 330); of which AKI was observed in 3 of 110 (2.7%) versus 35 of 330 (10.6%), respectively (P=0.01). A multivariate logistic regression analysis revealed that weight (OR: 1.02; 95% CI: 1.006 to 1.03; P-=0.005) and intensive care unit admission (OR: 6.88; 95% CI: 2.96 to 18.8; P<0.001) were independently associated with AKI, while montelukast (OR: 0.26; 95% CI: 0.06 to 0.77; P=0.03) and male gender were protective (OR: 0.41; 95% CI: 0.19 to 0.85; P=0.02). Our in vitro model also revealed that adjuvant montelukast can reduce injury to proximal tubule cells through activation of the p62/KEAP-1/HO-1 antioxidant pathway. Our study suggests that montelukast during vancomycin therapy may be protective against AKI, which may reduce patient harm and hospitalization costs. Further studies are warranted to validate our findings prospectively.

Abstract 4135465: Efficacy of SGLT-2 inhibitors combined with percutaneous coronary intervention on clinical and echocardiographic parameters in patients with acute myocardial infarction: A systematic review and meta-analysis

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular outcomes in heart failure (HF) patients and may mitigate symptom progression in myocardial infarction (MI). However, their efficacy in acute MI patients undergoing percutaneous coronary intervention (PCI) is unclear. This study aims to evaluate whether SGLT2i combined with PCI improves clinical and echocardiographic outcomes. Methods: A comprehensive search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from inception till May 2024. The study was conducted adhering to the PRISMA guidelines. The clinical benefit of PCI plus SGLT2i was assessed through risk reduction of acute kidney injury (AKI), CV death (CVD), hospitalization due to HF (hHF), all-cause mortality (ACM), and revascularization. Echocardiographic outcomes assessed were change in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (LVEDV). Results were presented as risk ratios (RR) along with their 95% CI for dichotomous data while weighted mean difference (WMD) were reported for continuous outcomes. The data was aggregated using a random effects model. Results: Our analysis included eleven records comprising 6,411 participants. The results indicated that PCI plus SGLT2i significantly reduced the risk of AKI (RR: 0.66, 95% CI: [0.52, 0.83], p&lt;0.01) and ACM (RR: 0.54, 95% CI: [0.4, 0.7], p&lt;0.01) compared to PCI alone. However, the reduction in risk for CVD was not statistically significant (RR: 0.56, 95% CI: [0.2, 1.1], p=0.09), as was the case for hHF (RR: 0.65, 95% CI: [0.3, 1], p=0.07). Additionally, there was no significant difference in the risk of revascularization between the two groups (RR: 2.9, 95% CI: [0.62, 14.39], p=0.17). PCI plus SGLT2i was also significantly associated with an increase in LVEF (WMD: 2.73, 95% CI: [1.09, 4.36], p&lt;0.01) and decrease in LVEDV (WMD: -8.0, 95% CI: [-13.17, -2.90], p&lt;0.02). Conclusion: Our study demonstrates that SGLT2i administration in MI patients undergoing PCI leads to improved renal and mortality outcomes, along with enhanced cardiac function. These benefits are hypothesized to result from kidney-mediated natriuretic effects, improved blood flow regulation, reduced endothelial dysfunction, and decreased arterial stiffness, which optimize cardiac function. We recommend future studies with larger sample sizes and longer follow-ups to assess the long-term benefits of SGLT2i combined with PCI.

Adverse effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.

Reduction of acute kidney injury in pediatric patients after bone marrow transplant: A prospective analysis after quality improvement implementation.

371 Background: Hematopoietic cell transplantation (HCT) is a curative therapy for malignant and non-malignant diseases. Acute kidney injury (AKI) is a common complication after HCT secondary to use of nephrotoxic medications (NTMx) prescribed for conditioning and prophylaxis. A recently published meta-analysis estimates the incidence of AKI after HCT to be 55.1%, with Stage 3 occurring in 8.3% of patients. Nephrotoxic medication–associated AKI (NAKI) affects 19%–31% of children who receive an intravenous aminoglycoside, with NAKI rates doubling with receipt of ≥ 3 nephrotoxic medications on the same day. We hypothesized that reducing NTMx exposure in pediatric HCT patients would be associated with lower all causes AKI incidence in the HCT unit. Methods: Single-center harm-preventing measures have been implemented at our center since 2019 to 2023. A multi-phased approach was used to increase education and recognition surrounding NTMx exposures in the HCT unit and role in subsequent AKI. We identified champions in the Pediatric HCT and Infectious Disease Host Defense teams. Five educational sessions took place from November 2022-June 2023 and an informational handout was created and distributed to HCT providers. Notifications to attending physicians of patients meeting NTMx exposure criteria, with acceptable alternatives to commonly used nephrotoxic drugs, and suggestions for AKI monitoring took place during daily rounds by the clinical pharmacist. Data on exposures and NAKIs’ was collected and reviewed every 3 months. Results: The cohort included 79 unique patients with 3547 patient days admitted to the HCT unit at Nationwide Children’s Hospital between January 1 2022 and March 31 2023. A total of 210 NTMx exposures were identified and resulted in 22 NAKI events. We reduced the rates of nephrotoxic medication exposure by 51% from 14.36 to 7 per month per 1000 patient days and NAKIs by 21% from to 1.27 to 1 per month per 1000 patient days since the start of our interventions. Conclusions: Successful interventions to decrease AKI in patients admitted to the HCT unit require a multi-disciplinary, iterative, and continuous approach, including recurrent education efforts to providers and pharmacy-driven daily physician alerts. Organizational implementation of these interventions is still ongoing.

A Risk-Prediction Platform for Acute Kidney Injury and 30-Day Readmission After Colorectal Surgery

IntroductionFew known risk factors for certain surgical complications are prospectively analyzed to ascertain their influence on outcomes. Health systems can use integrated machine-learning-derived algorithms to provide information regarding patients' risk status in real time and pair this data with interventions to improve outcomes. The purpose of this work was to evaluate whether real-time knowledge of patients’ calculated risk status paired with a stratified intervention was associated with a reduction in acute kidney injury and 30-d readmission following colorectal surgery. MethodsUnblinded, retrospective study, evaluating the impact of an electronic health record-integrated and autonomous algorithm-based clinical decision support tool (KelaHealth, San Francisco, California) on acute kidney injury and 30-d readmission following colorectal surgery at a single academic medical center between January 1, 2020, and December 31, 2020, relative to a propensity-matched historical cohort (2014-2018) prior to algorithm integration (January 11, 2019). Results3617 patients underwent colorectal surgery during the control period and 665 underwent surgery during the treatment period; 1437 historical control patients were matched to 479 risk-based patients for the study. Utilization of the risk-based management platform was associated with a 2.5% decrease in the rate of acute kidney injury (11.3% to 8.8%) and 3.1% decrease in rate of readmissions (12% to 8.9%). ConclusionsIn this study, we found significant reductions in postoperative acute kidney injury (AKI) and unplanned readmissions after the implementation of an algorithm based clinical decision support tool that risk-stratified populations and offered stratified interventions. This opens up an opportunity for further investigation in translating similar risk platform approaches across surgical specialties.

C26 SIDE EFFECTS OF SGLT–2 INHIBITORS IN PATIENTS WITH HEART FAILURE: A META–ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract Background sodium–glucose cotransoporter–2 inhibitors (SGLT–2Is) improve prognosis in heart failure patients both with reduced (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. Purpose: estimate the relative risk of side effects in HF patients treated with SGLT–2Is irrespectively from left ventricular EF and setting (acute and chronic HF). Methods 4 randomized controlled trials (RCTs) enrolling patients with HFrEF 3 RCTs enrolling acute HF and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury diabetic ketoacidosis, hypotension, hypoglycemia, hyperkalemia, hypokalemia, bone fractures and amputations were considered in the analysis. Results overall 22687 patients were included in the analysis: 8830 (39%) patients with HFrEF, 12563 (55%) with HFpEF and 1295 (6%) with acute HF. There weren’t differences between SGLT–2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures and amputations. HFrEF patients treated with SGLT–2is had a significative reduction of acute kidney injury [RR 0.54; 95% CI 0.33–0.87) p= 0.011], whereas no differences have been reported in the HFpEF [RR 0.94 (95% CI 083–1.07) p=0.348] and acute setting [RR 0.97; 95% CI 0.58–1.64) p= 0.915] (Fig 1A). A higher risk to develop genital infection [overall 2.82; 95% CI 1.96–4.05) p &amp;lt;0.001] was found irrespectively from EF [HFrEF 2.38 (95%CI 1.34–4.24) p= 0.003; HFpEF RR 3.04 (95%CI 1.88–4.90) p &amp;lt;0.001] (Fig 1B). The risk to develop urinary infections and hypotension was increased in the overall HF population with a RR of 1.15 (95%CI 1.02–1.30) p= 0.028 and RR 1.15; 95%CI 1.02–1.29) p= 0.017, respectively (Fig 2 A–B). This risk was mainly driven by HFpEF patients [RR urinary infections 1.19 (95%CI 1.02–1.38) p= 0.029; RR hypotension 1.23 (95% CI 1.05–1.43) p= 0.011], whereas no differences have been reported in HFrEF [RR urinary infection 1.04 (95%CI 0.80–1.35) p= 0.774; RR hypotension 1.04 (95%CI 0.87–1.24) p= 0.687] and in the acute setting [RR urinary infections 1.19 (95%CI 0.81–1.74) p= 0.375; RR hypotension 1.23 (95%CI 0.78–1.96) p= 0.371]. Conclusions SGLT–2is increase the risk of genital infections in HF patients. In HFpEF patients SGLT–2Is increase the risk of urinary infections and hypotension compared to placebo, whereas reduce the risk of acute kidney disease in patients with HfrEF.

A norepinephrine weaning strategy using dynamic arterial elastance is associated with reduction of acute kidney injury in patients with vasoplegia after cardiac surgery: A post-hoc analysis of the randomized SNEAD study.

Study objectiveTo evaluate the impact of a dynamic arterial elastance guided norepinephrine weaning strategy on the occurrence of acute kidney injury (AKI) in patients with vasoplegia after cardiac surgery. DesignA post-hoc analysis of a monocentric randomized controlled trial. SettingA tertiary care hospital in France. ParticipantsVasoplegic cardiac surgical patients treated with norepinephrine. InterventionPatients were randomized to an algorithm-based norepinephrine weaning intervention (dynamic arterial elastance) group or a control group. MeasurementsThe primary endpoint was the number of patients with AKI defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The secondary endpoint were major adverse cardiac post-operative events (new onset of atrial fibrillation or flutter, low cardiac output syndrome, and in-hospital death). End points were evaluated during the first seven post-operative days. Results118 patients were analyzed. In the overall study population, the mean age was 70 (62–76) years, 65% were male and the median EuroSCORE was 7 (5–10). Overall, 46 (39%) patients developed AKI (30 KDIGO 1, 8 KDIGO 2, 8 KDIGO 3), and 6 patients required renal replacement therapy. The incidence of AKI was significantly lower in the intervention group than in the control group (16 patients (27%) vs 30 patients (51%), p = 0.12). Higher dose and longer duration of norepinephrine were associated with AKI severity. ConclusionDecreasing norepinephrine exposure by using a dynamic arterial elastance guided norepinephrine weaning strategy was associated with a reduced incidence of acute kidney injury in patients with vasoplegia after cardiac surgery. Further prospective multicentric studies are needed to confirm these results.

Association of Perioperative Cryoprecipitate Transfusion and Mortality After Cardiac Surgery

BackgroundCryoprecipitate is often transfused in patients undergoing cardiac surgery. However, its safety and effectiveness remain uncertain. MethodsThis study was a propensity score–matched analysis of data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. The study included adults undergoing cardiac surgery between 2005 and 2018 across 38 sites. The association between perioperative cryoprecipitate transfusion and clinical outcomes was estimated, with a primary outcome of operative mortality. ResultsOf 119,132 eligible patients, 11,239 (9.43%) patients received cryoprecipitate. The median cumulative dose was 8 U (interquartile range, 5-10 U). After propensity score matching, we matched 9055 cryoprecipitate recipients to 9055 control subjects. Postoperative cryoprecipitate transfusion was associated with reduced operative mortality (odds ratio [OR], 0.82; 99% CI, 0.69-0.97; P = .002) and long-term mortality (hazard ratio, 0.92; 99% CI, 0.87-0.97; P = .0042). It was also associated with a reduction in acute kidney injury (OR, 0.85; 99% CI, 0.73-0.98; P = .0037) and all-cause infection (OR, 0.77; 99% CI, 0.67-0.88; P < .0001). These findings were observed despite increased rates of return to the operating room (OR, 1.36; 99% CI, 1.22-1.51; P < .0001) and cumulative 4-hour postoperative chest tube output (adjusted mean difference in mL, 97.69; 99% CI, 81.65;113.74; P < .0001). ConclusionsIn a large, multicenter cohort study and after propensity score matching, perioperative transfusion of cryoprecipitate was associated with reduced operative and long-term mortality.

Urea Reduction in Acute Kidney Injury and Mortality Risk

Introduction: Urea is a toxin present in acute kidney injury (AKI). We hypothesize that reduction in serum urea levels might improve clinical outcomes. We examined the association between the reduction in urea and mortality. Methods: Patients with AKI admitted to the Hospital Civil de Guadalajara were enrolled in this retrospective cohort study. We create 4 groups of urea reduction ratio (UXR) stratified by their decrease in urea from the highest index value in comparison to the value on day 10 (0%, 1–25%, 26–50%, and >50%), or at the time of death or discharge if prior to 10 days. Our primary endpoint was to observe the association between UXR and mortality. Secondary observations included determination of which types of patients achieved a UXR >50%, whether the modality of kidney replacement therapy (KRT) effected changes in UXR, and if serum creatinine (sCr) value changes were similarly associated with patient mortality. Results: A total of 651 AKI patients were enrolled. The mean age was 54.1 years, and 58.6% were male. AKI 3 was present in 58.5%; the mean admission urea was 154 mg/dL. KRT was started in 32.4%, and 18.9% died. A trend toward decreased risk of death was observed in association with the magnitude of UXR. The best survival (94.3%) was observed in patients with a UXR >50%, and the highest mortality (72.1%) was observed in patients achieving a UXR of 0%. After adjusting for age, sex, diabetes mellitus, CKD, antibiotics, sepsis, hypovolemia, cardio-renal syndrome, shock, and AKI stage, the 10-day mortality was higher in groups that did not achieve a UXR of at least 25% (OR: 1.20). Patients achieving a UXR >50% were most likely initiated on dialysis due to a diagnosis of the uremic syndrome or had a diagnosis of obstructive nephropathy. Percentage change in sCr was also associated with increased mortality risk. Conclusions: In our retrospective cohort of AKI patients, the percent decrease in UXR from admission was associated with a stratified risk of death. Patients with a UXR >25% had the best associated outcomes. Overall, a greater magnitude in UXR was associated with improved patient survival.

941. Clinical Outcomes of Vancomycin Area-Under-the-Curve Monitoring: A Quasi-Experimental Study Interim Analysis

Abstract Background The 2020 Infectious Diseases Society of America vancomycin guidelines recommend the use of area-under-the-curve (AUC) monitoring instead of trough concentration monitoring. These guidelines changed due to evidence showing decreased rates of nephrotoxicity and lack of correlation between vancomycin troughs and patient treatment outcomes. Two common methodologies of calculating AUC exist in clinical practice, including two level kinetic calculations and Bayesian software programs. Previous studies used two levels for calculating the AUC. The purpose of this study is to evaluate if the same reduction in acute kidney injury (AKI) is achieved while using a Bayesian software program. Methods This retrospective quasi-experiment was performed at two sites within the same health system. The primary objective of this study was to assess the rate of AKI, as defined by the Acute Kidney Injury Network (AKIN) criteria, between patients receiving vancomycin dosed by trough monitoring as compared to AUC monitoring. Secondary objectives include mean daily dose of vancomycin, number of vancomycin levels, and severity of AKI. Patients were included in the study if they were 18 years or older, with at least one vancomycin concentration drawn. Patients were excluded if they had a baseline serum creatine greater than 2 mg/dL, received renal replacement therapy of any type, or received &amp;gt; 1 doses of vancomycin prior to admission. After screening for inclusion criteria, patients were matched 1:1 based on APACHE II score and vancomycin indication. Results One hundred and thirty patients met inclusion criteria at the interim analysis. Overall, baseline characteristics were similar between groups. No statistical difference was detected regarding the rate of acute kidney injury between the vancomycin trough group and AUC group (12% vs 14% p=0.971). The mean total daily doses of vancomycin were 1642 mg per day in the AUC group and 1838 mg per day in the trough group (p=0.08). Conclusion No statistical difference in rates of AKI were detected at the interim analysis, likely due to small sample size. Further data collection is ongoing to meet power and full results will be presented. Disclosures All Authors: No reported disclosures.

Long-Term Healthcare Cost Savings of a Pediatric Nephrotoxic Medication-Associated Acute Kidney Injury Reduction Program in a Simulated Sample

Background: Nephrotoxic medication exposure is a common cause of acute kidney injury (AKI) in hospitalized children and is associated with chronic kidney disease (CKD). The pharmacist-reliant NINJA program reduced nephrotoxic medication exposure and associated AKI. Objectives: We assess potential healthcare cost savings from reduced CKD by preventing AKI with the NINJA program for a pediatric population through age 21. Methods: We simulated a cohort of 1000 hospitalized non-critically ill children. From the published literature, 310 develop AKI, 267 survive to 6 months, and 10-70% develop CKD, and NINJA implementation reduced AKI by 23.8%. Allowing for varying CKD rates, we estimated a range of NINJA’s savings. We assumed an annual GFR decline of 1.2 (noHTN) ml/min/1.73 m2 for half the sample and 1.7 (HTN) ml/min/1.73 m2 for the other half to account for CKD progression without and with hypertension (HTN). We model attributable costs including CKD stage-related medications and outpatient visits/tests in 2018 dollars discounted at 3%. We subtract the cost of NINJA screening (daily serum creatinine and pharmacist time) from net savings. We exclude end-stage renal disease (ESRD) and hospitalization costs. Results: No intervention estimated CKD related costs are $761,852 to $5,735,027. Post-NINJA cost decreases to $616,086 to $4,312,183 (net savings: $145,766 to $1,422 183). Total savings, accounting for NINJA screening ($256,680) are -$110,914 to $1,1 165 503. The breakeven AKI to CKD conversion rate is 13-14% with growth hormone cost included, and 64-65% without. Conclusion: The NINJA program is likely cost beneficial, with greater savings into adulthood by avoiding/delaying ESRD and its costs.

A Prediction Model for Acute Kidney Injury After Pericardiectomy: An Observational Study.

ObjectivesAcute kidney injury is a common complication after pericardiectomy for constrictive pericarditis, which predisposes patients to worse outcomes and high medical costs. We aimed to investigate potential risk factors and consequences and establish a prediction model.MethodsWe selected patients with constrictive pericarditis receiving isolated pericardiectomy from January 2013 to January 2021. Patients receiving concomittant surgery or repeat percardiectomy, as well as end-stage of renal disease were excluded. Acute kidney injury was diagnosed and classified according to the KDIGO criteria. Clinical features were compared between patients with and without postoperative acute kidney injury. A prediction model was established based on multivariable regression analysis.ResultsAmong two hundred and eleven patients, ninety-five (45.0%) developed postoperative acute kidney injury, with fourty-three (45.3%), twenty-eight (29.5%), and twenty-four (25.3%) in mild, moderate and severe stages, respectively. Twenty-nine (13.7%) patients received hemofiltration. Nine (4.3%) patients died perioperatively and were all in the acute kidney injury (9.5%) group. Eleven (5.2%) patients were considered to have chronic renal dysfunction states at the 6-month postoperative follow-up, and eight (72.7%) of them experienced moderate to severe stages of postoperative acute kidney injury. Univariable analysis showed that patients with acute kidney injury were older (difference 8 years, P < 0.001); had higher body mass index (difference 1.68 kg·m−2, P = 0.002); rates of smoking (OR = 2, P = 0.020), hypertension (OR = 2.83, P = 0.004), and renal dysfunction (OR = 3.58, P = 0.002); higher central venous pressure (difference 3 cm H2O, P < 0.001); and lower cardiac index (difference −0.23 L·min−1·m−2, P < 0.001) than patients without acute kidney injury. Multivariable regression analysis showed that advanced age (OR 1.03, P = 0.003), high body mass index (OR 1.10, P = 0.024), preoperative atrial arrhythmia (OR 3.12, P = 0.041), renal dysfunction (OR 2.70 P = 0.043), high central venous pressure (OR 1.12, P = 0.002), and low cardiac index (OR 0.36, P = 0.009) were associated with a high risk of postoperative acute kidney injury. A nomogram was established based on the regression results. The model showed good model fitness (Hosmer-Lemeshow test P = 0.881), with an area under the curve value of 0.78 (95% CI: 0.71, 0.84, P < 0.001).ConclusionThe prediction model may help with early recognition, management, and reduction of acute kidney injury after pericardiectomy.

Acute kidney injury reduction with SGLT-2 inhibitors?

Acute kidney injury reduction with SGLT-2 inhibitors?

Liquid plasma: A solution to optimizing early and balanced plasma resuscitation in massive transfusion

Early and balanced resuscitation for traumatic hemorrhagic shock is associated with decreased mortality, making timely plasma administration imperative. However, fresh frozen plasma (FFP) thaw time can delay administration, and the shelf life of thawed FFP limits supply and may incur wastage. Liquid plasma (LP) offers an attractive alternative given immediate transfusion potential and extended shelf life. As such, we hypothesized that the use of LP in the massive transfusion protocol (MTP) would improve optimal plasma/red blood cell (RBC) ratios, initial plasma transfusion times, and clinical outcomes in the severely injured patient. Using Trauma Quality Improvement Program data from our level 1 trauma center, we evaluated MTP activations from 2016 to 2018. Type A LP use was instated April 2017. Before this, thawed FFP was solely used. Plasma/RBC ratios and initial plasma transfusion times were compared in MTP patients before and after LP implementation. Patient and injury characteristics were accounted for using linear regression analysis. Secondary outcomes of mortality, 28-day recovery, and complications were evaluated using Cox proportional hazards regression. A total of 95 patients were included (pre-LP, 39; post-LP, 56). Time to initial plasma transfusion and plasma/RBC ratios at 4 and 24 hours were improved post-LP implementation with a coinciding reduction in RBC units transfused (p < 0.05). In a 28-day Cox proportional hazards regression LP implementation was associated with favorable recovery (hazard ratio, 3.16; 95% confidence interval, 1.60-6.24; p < 0.001) and reduction in acute kidney injury (hazard ratio, 0.092; 95% confidence interval, 0.011-0.77; p = 0.027). No post-LP patients with blood group type B or AB (n = 9) demonstrated evidence of hemolysis within 24 hours of type A LP transfusion. Initial resuscitation with LP optimizes early plasma administration and improves adherence to transfusion ratio guidelines. Furthermore, LP offers a solution to inherent delays with FFP and is associated with improved clinical outcomes, particularly 28-day recovery and odds of acute kidney injury. Liquid plasma should be considered as an alternative to FFP in MTPs. Therapeutic/care management, level IV.

Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: A Systematic Review and Meta-Analysis.

Critically ill patients routinely receive vancomycin as empiric antibiotic therapy. A continuous infusion administration strategy may be superior to intermittent infusion by minimizing peak concentrations and variability thereby optimizing safety. We performed a systematic review and meta-analysis to investigate the impact of vancomycin infusion strategy on acute kidney injury in critically ill adults. A systematic search of MEDLINE, CINAHL, Web of Science, International Pharmaceutical Abstracts, and Google Scholar was undertaken. We included randomized controlled trials and observational studies evaluating acute kidney injury in critically ill adults comparing vancomycin administered by intermittent and continuous infusion. Secondary outcomes included mortality and pharmacokinetic target attainment. Eleven studies were identified for analysis with baseline demographics, endpoints, protocol definitions, and outcomes extracted. When compared with intermittent infusion, continuous infusion was associated with a reduction in acute kidney injury in critically ill adults (odds ratio, 0.47; 95% CI, 0.34-0.65) and a 2.6 greater odds of pharmacokinetic target attainment (odds ratio, 2.63; 95% CI, 1.52-4.57). No difference in mortality was observed (odds ratio, 1.04; 95% CI, 0.80-1.35). When administered via a continuous infusion, vancomycin is associated with a 53% reduction in the odds of acute kidney injury and a 2.6-fold higher odds of pharmacokinetic target attainment when compared with intermittent infusion without influencing overall mortality.

Differential Effects of the Mitochondria-Active Tetrapeptide SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2) and Its Peptidase-Targeted Prodrugs in Experimental Acute Kidney Injury.

The mitochondria-active tetrapeptide SS-31 can control oxidative tissue damage in kidney diseases. To investigate other potential beneficial nephroprotective effects of SS-31, in vivo murine models of acute tubular injury and glomerular damage were developed. Reduction of acute kidney injury was demonstrated in mice treated with SS-31. The expression of mRNAs involved in acute inflammatory and oxidative stress responses in the diseased kidneys confirmed that SS-31 could regulate these pathways in our in vivo models. Furthermore, ex vivo histoenzymography of mouse kidneys showed that aminopeptidase A (APA), the enzyme involved in the processing of angiotensin (Ang) II to Ang III, was induced in the diseased kidneys, and its activity was inhibited by SS-31. As the renin–angiotensin system (RAS) is a main regulator of kidney functions, the modulation of Ang receptors (ATR) and APA by SS-31 was further investigated using mRNAs extracted from diseased kidneys. Following acute tubular and/or glomerular damage, the expression of the AT1R mRNA was upregulated, which could be selectively downregulated upon SS-31 administration to the animals. At the same time, SS-31 was able to increase the expression of the AT2R, which may contribute to limit renal damage. Consequently, SS-31-based prodrugs were developed as substrates and/or inhibitors for APA and were screened using cells expressing high levels of APA, showing its selective regulation by α-Glu-SS-31. Thus, a link between SS-31 and the RAS opens new therapeutic implications for SS-31 in kidney diseases.

OUTCOMES SUTURELESS AORTIC VALVE REPLACEMENT VERSUS CONVENTIONAL AORTIC VALVE REPLACEMENT AND TRANSCATHETER AORTIC VALVE REPLACEMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS

Sutureless aortic valve replacement (SuaVR) is a feasible alternative to conventional aortic replacement (SAVR) and transcatheter aortic valve replacement (TAVR). The aim of this study is to compare the effectiveness of the SuAVR versus SAVR, and SuAVR versus TAVR. We searched MEDLINE and EMBASE from inception to August 2018 for adjusted observational studies evaluating SuAVR, SAVR, and TAVR in adult patients with aortic stenosis. Independently and in duplicate, we performed screening, full-text assessment, risk of bias evaluation using the CLARITY tool. We pooled data using a random-effects model. We evaluated the quality of evidence using the GRADE framework. Of the references, 34 studies including 7979 participants (SuAVR versus SAVR= 6831; SuAVR versus TAVR= 1148) conducted between 2012 and 2018 were included. Overall, studies were judged to be at unclear risk of bias. Compared to SAVR and TAVR, SuAVR was associated with similar postoperative mean transvalvular gradients (mean difference]MD [: –1.00; 95% CI, -2.76 to 0.76; P=0.27) and (MD: 0.50; 95% CI, 0.27 to 1.28; P=0.20) respectively. Compared to TAVR, SuAVR showed a reduction in mortality at 30 days (odds ratio (OR): 0.36; 95% CI, 0.17 to 0.73; P=0.005) and 2 years (OR: 0.39, 95 CI, 0.17 to 0.88; P=0.003). Reduction in mortality did not reach statistical significance in high risk (OR:0.16, 95% CI, 0.02 to 1.35; P=0.09) or intermediate risk patients (OR: 0.76, 95% CI, 0.32 to 1.82, P=0.54). Compared to TAVR, SuAVR showed reduction in mild (OR: 0.09, 95% CI, 0.03 to 0.26, P=0.000) and moderate paravalvular leaks (OR: 0.11, 95% CI, 0.02 to 0.61, P=0.01). Moreover, SuAVR showed significant reduction in acute kidney injury compared to TAVR (OR: 0.50, 95 % CI, 0.27 to 0.91, P=0.02) and comparable reduction to SAVR (OR: 0.89, 95% CI, 0.45 to 1.76, P=0.47). Compared to SAVR, SuAVR showed a similar reduction in mortality at 30 days (OR: 1.01, 95 % CI, 0.72 to 1.42, P=0.93) and at 2 years (OR: 0.99, 95 % CI, 0.43 to 2.30, P= 0.30). These results were rated low-quality evidence using the GRADE framework. While the use of sutureless aortic valves is increasing with similar short and midterm outcomes compared to TAVR and SAVR, the quality of evidence supporting its utilization is low, even with matched patients. Comparative randomized data with long-term follow up is required to elucidate the role of SuAVR.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Meta-Analysis of Trials on Prophylactic Use of Levosimendan in Patients Undergoing Cardiac Surgery

The role of prophylactic levosimendan in patients undergoing cardiac surgery is controversial. We performed a computerized search of Medline, Embase, and Cochrane databases through September 2017 for randomized trials evaluating the prophylactic use of levosimendan in patients undergoing cardiac surgery (ie, patients without low cardiac output syndrome). The main study outcome was mortality at 30 days. The final analysis included 16 randomized trials with total of 2,273 patients. There was no statistically significant difference in mortality at 30 days between levosimendan and control groups (relative risk 0.68, 95% confidence interval [CI]: 0.45 to 1.03). Subgroup analysis showed no statistically significant difference in mortality at 30 days for patients with reduced left ventricular ejection fraction compared with patients having preserved left ventricular ejection fraction (p for interaction= 0.12). Further analysis suggested that levosimendan might be associated with improved mortality at 30 days when compared with active-control but not when compared with placebo (p for interaction= 0.01). The levosimendan group had a significant reduction in acute kidney injury (relative risk 0.59, 95% CI: 0.38 to 0.92), intensive care unit stay (standardized mean difference=-0.21, 95% CI:-0.29 to-0.13), and ventilation time (standardized mean difference=-0.43, 95% CI:-0.61 to-0.25), whereas it had higher rates of atrial fibrillation (relative risk 1.11, 95% CI: 1.00 to 1.24). No statistically significant differences were observed between groups in mortality beyond 30 days, postoperative dialysis, or myocardial infarction. Prophylactic use of levosimendan does not appear to reduce the mortality at 30 days or beyond 30 days in patients undergoing cardiac surgery. This lack of benefit was noted irrespective of the LVEF.

Adjunction of a MEK inhibitor to Vemurafenib in the treatment of metastatic melanoma results in a 60% reduction of acute kidney injury.

A combined therapy MEK inhibitor, Cobimetinib (CB) and BRAF inhibitor, Vemurafenib (VMF), results in an improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma. VMF skin adverse effects attributed to ERK paradoxical activation are decreased by the adjunction of CB. The aim of this study was to determine if this combination also improved the renal side effects of VMF. To investigate the incidence of acute kidney injury (AKI), we conducted a retrospective observational monocentric study in Lyon Sud University Hospital in France. We included 38 patients with metastatic BRAF-mutated melanomas treated by VMF and CB between March 2015 and June 2016. According to the NCI-CTCAE classification, AKI was defined as an increase in serum creatinine exceeding the baseline concentration by 1.5-fold. Serum creatinine was measured before treatment, then on a monthly basis during treatment, and 1month after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-), and further subdivided into three groups according to AKI severity (stage 1-5). Of 38 patients, 29 (76%) were AKI-, and all 9 AKI+ patients (24%) were diagnosed within the first trimester of treatment. Three-quarters of AKI (n = 7, 77%) had stage 1 AKI and the remaining 23% stage 2 AKI. Pre-treatment renal function was significantly better in AKI+ group: 105 vs. 80ml/min/1.73m² AKI-, p = 0.009. Compared to previous results, the AKI incidence under the combined VMF-CB vs. VMF monotherapy was reduced by 60%. We reported a reduced incidence and severity of nephrotoxicity of the association inhibitors of BRAF and MEK compared to a BRAF inhibitor monotherapy.