CCL14 testing to guide clinical practice in patients with AKI: Results from an international expert panel.

PURPOSE: Urinary C-C motif chemokine ligand 14 (CCL14) is a strong predictor of persistent stage 3 acute kidney injury (AKI). Multiple clinical actions are recommended for AKI but how these are applied in individual patients and how the CCL14 test results may impact their application is unknown. METHODS: We assembled an international panel of 12 experts and conducted a modified Delphi process to evaluate patients at risk for persistent stage 3 AKI (lasting 72 hours or longer). Using a Likert scale, we rated 11 clinical actions based on international guidelines applied to each case before and after CCL14 testing and analyzed the association between the strength and direction of recommendations and CCL14 results. RESULTS: The strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for the interaction). Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results (P < 0.001 comparing low to highest CCL14 risk category). CONCLUSIONS: Most recommendations for care of patients with stage 2-3 by an international panel of experts were strongly modified by CCL14 test results. This work should set the stage for clinical practice protocols and studies to determine the effects of recommended actions informed by CCL14.

A pilot study to explore patterns and predictors of delayed kidney decline after cardiopulmonary bypass.

There is no current consensus on the follow up of kidney function in patients undergoing cardiopulmonary bypass (CPB). The main objectives of this pilot study is to collect preliminary data on kidney function decline encountered on the first postoperative visit of patients who have had CPB and to identify predictors of kidney function decline post hospital discharge. Design: Retrospective chart review. Adult patients undergoing open heart procedures utilizing CPB. Patient demographics, type of procedure, pre-, intra-, and postoperative clinical, hemodynamic echocardiographic, and laboratory data were abstracted from electronic medical records. Acute kidney disease (AKD), and chronic kidney disease (CKD) were diagnosed based on standardized criteria. Interval change in medications, hospital admissions, and exposure to contrast, from hospital discharge till first postoperative visit were collected. AKD, and CKD as defined by standardized criteria on first postoperative visit. 83 patients were available for analysis. AKD occurred in 27 (54%) of 50 patients and CKD developed in 12 (42%) out of 28 patients. Older age was associated with the development of both AKD and CKD. Reduction in right ventricular cardiac output at baseline was associated with AKD (OR: 0.5, 95% CI: 0.3, 0.79, P = 0.01). Prolongation of transmitral early diastolic filling wave deceleration time was associated with CKD (OR: 1.02, 95% CI: 1.01, 1.05, P = 0.03). In-hospital acute kidney injury (AKI) was a predictor of neither AKD nor CKD. AKD and CKD occur after CPB and may not be predicted by in-hospital AKI. Older age, right ventricular dysfunction and diastolic dysfunction are important disease predictors. An adequately powered longitudinal study is underway to study more sensitive predictors of delayed forms of kidney decline after CPB.

Evaluation of Clinical and Machine Data of Critically Ill Adult COVID Patients with Acute Kidney Injury Exposed to Enhanced Hemoadsorption during CRRT.

INTRODUCTION: The FDA authorized the emergency use of enhanced hemoadsorption with oXiris in critically ill adult COVID patients with respiratory failure or severe disease to reduce inflammation. In this study, we evaluated critically ill adult COVID patients with acute kidney injury (AKI) who were exposed versus not exposed to enhanced hemoadsorption with oXiris during continuous renal replacement therapy (CRRT). METHODS: Retrospective cohort study of critically ill adult COVID patients with AKI requiring CRRT. Exposure to oXiris was defined as receiving oXiris for >12 cumulative hours and more than one-third of the time within the first 72 h of CRRT. Study outcomes included filter-specific performance metrics and clinical outcomes such as ventilator requirement, mortality, and dialysis dependence. Inverse probability treatment weighting was used to balance potential confounders in weighted regression models. RESULTS: 14,043 h of CRRT corresponding to 85 critically ill adult patients were analyzed. Among these, 2,736 h corresponded to oXiris exposure (n = 25 patients) and 11,307 h to a standard CRRT filter (n = 60 patients). Transmembrane pressures (TMPs) increased rapidly and were overall higher with oXiris versus standard filter, but filter life (median of 36.3 vs. 33.1 h, p = 0.913, respectively) and filter/clotting alarms remained similar in both groups. In adjusted models, oXiris exposure was not independently associated with the composite of hospital mortality and dialysis dependence at discharge (OR 2.13, 95% CI: 0.98-4.82, p = 0.06), but it was associated with fewer ventilator (ß = -15.02, 95% CI: -29.23 to -0.82, p = 0.04) and intensive care unit days (ß = -14.74, 95% CI: -28.54 to -0.95, p = 0.04) in survivors. DISCUSSION/CONCLUSION: In critically ill adult COVID patients with AKI requiring CRRT, oXiris filters exhibited higher levels of TMP when compared to a standard CRRT filter, but no differences in filter life and filter/clotting alarm profiles were observed. The use of oXiris was not associated with improvement in clinical outcomes such as hospital mortality or dialysis dependence at discharge.

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

Acute kidney injury in neurocritical care.

Approximately 20% of patients with acute brain injury (ABI) also experience acute kidney injury (AKI), which worsens their outcomes. The metabolic and inflammatory changes associated with AKI likely contribute to prolonged brain injury and edema. As a result, recognizing its presence is important for effectively managing ABI and its sequelae. This review discusses the occurrence and effects of AKI in critically ill adults with neurological conditions, outlines potential mechanisms connecting AKI and ABI progression, and highlights AKI management principles. Tailored approaches include optimizing blood pressure, managing intracranial pressure, adjusting medication dosages, and assessing the type of administered fluids. Preventive measures include avoiding nephrotoxic drugs, improving hemodynamic and fluid balance, and addressing coexisting AKI syndromes. ABI patients undergoing renal replacement therapy (RRT) are more susceptible to neurological complications. RRT can negatively impact cerebral blood flow, intracranial pressure, and brain tissue oxygenation, with effects tied to specific RRT methods. Continuous RRT is favored for better hemodynamic stability and lower risk of dialysis disequilibrium syndrome. Potential RRT modifications for ABI patients include adjusted dialysate and blood flow rates, osmotherapy, and alternate anticoagulation methods. Future research should explore whether these strategies enhance outcomes and if using novel AKI biomarkers can mitigate AKI-related complications in ABI patients.

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.

Continuous KRT: A Contemporary Review.

AKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.

Assessment of prescribed vs. achieved fluid balance during continuous renal replacement therapy and mortality outcome.

BACKGROUND: Fluid management during continuous renal replacement therapy (CRRT) requires accuracy in the prescription of desired patient fluid balance (FBGoal) and precision in the attainable patient fluid balance (FBAchieved). Herein, we examined the association of the gap between prescribed vs. achieved patient fluid balance during CRRT (%FBGap) with hospital mortality in critically ill patients. METHODS: Cohort study of critically ill adults with acute kidney injury (AKI) requiring CRRT and a prescription of negative fluid balance (mean patient fluid balance goal of negative ≥0.5 liters per day). Fluid management parameters included: 1) NUF (net ultrafiltration rate); 2) FBGoal; 3) FBAchieved; and 4) FBGap (% gap of fluid balance achieved vs. goal), all adjusted by patient's weight (kg) and duration of CRRT (hours). RESULTS: Data from 653 patients (median of 102.2 patient-hours of CRRT) were analyzed. Mean (SD) age was 56.7 (14.6) years and 61.9% were male. Hospital mortality rate was 64%. Despite FBGoal was similar in patients who died vs. survived, survivors achieved greater negative fluid balance during CRRT than non-survivors: median FBAchieved -0.25 [-0.52 to -0.05] vs. 0.06 [-0.26 to 0.62] ml/kg/h, p<0.001. Median NUF was lower in patients who died vs. survived: 1.06 [0.63-1.47] vs. 1.22 [0.82-1.69] ml/kg/h, p<0.001, and median %FBGap was higher in patients who died (112.8%, 61.5 to 165.7) vs. survived (64.2%, 30.5 to 91.8), p<0.001. In multivariable models, higher %FBGap was independently associated with increased risk of hospital mortality: aOR (95% CI) 1.01 (1.01-1.02), p<0.001. NUF was not associated with hospital mortality when adjusted by %FBGap and other clinical parameters: aOR 0.96 (0.72-1.28), p = 0.771. CONCLUSIONS: Higher %FBGap was independently associated with an increased risk of hospital mortality in critically ill adults with AKI on CRRT in whom clinicians prescribed negative fluid balance via CRRT. %FBGap represents a novel quality indicator of CRRT delivery that could assist with operationalizing fluid management interventions during CRRT.

Acute Bronchiolitis: Why Put an IV Line?

BACKGROUND: Acute bronchiolitis is the most frequent cause of respiratory distress in pediatric emergency medicine. The risk of respiratory failure is frequently over evaluated, and results in systematic vascular access. METHODS: We conducted a prospective observational study in children under 18 months of age hospitalized for bronchiolitis. The aim of the study was to evaluate whether catheter insertion was useful for management. We monitored the number of catheters inserted in the emergency department and their subsequent use for rapid sequence intubation, adrenaline administration, or antimicrobial therapy. We recorded the number of secondary pediatric intensive care unit (ICU) admissions. RESULTS: We followed 162 patients and compared two populations, children with (population A, n = 35) and without (population B, n = 127) catheter insertion. There were no significant differences in age, oxygen saturation, heart rate, c-reactive protein, neutrophil count and the number of times nebulization was conducted at admission. Population A compared to B had a significantly higher temperature (38.1 ± 0.9 vs. 37.6 ± 0.7°C, P = 0.004) and respiratory rate (64 ±13 vs. 59 ±17, P = 0.033). Twelve patients were secondarily transferred to pediatric ICU, 3 from population A and 9 from B (NS). In a multivariate analysis, no significant relationship was found between ICU admission, venous access placement and potential confounding factors (pneumonia, age < 6 months, age < 3 months, food intake < 60%, temperature > 38° C, heart rate > 180 bpm, respiratory rate > 60/min, SpO2 < 95%, Spo2 < 90%, oxygen therapy, positive respiratory syncytial virus [RSV] sampling). Except for antimicrobial therapy (n = 32), catheters inserted in the emergency department were used in 5 patients for intravenous rehydration and in one patient in pediatric ICU for rapid sequence intubation. CONCLUSIONS: There were no life-threatening events that required immediate venous access for cardiopulmonary resuscitation. Medical treatment could be administered orally or via nasogastric tube in most cases. Peripheral catheterization was useless in immediate emergency management and only one child required a differed rapid sequence intubation.

Fluid Responsiveness in the Critically Ill Patient.

Accurate assessment of intravascular volume status in critically ill patients remains a very challenging task. Recent data have shown adverse outcomes in critically ill patients with either inadequate or overaggressive fluid therapy. Understanding the tools and techniques available for accurate volume assessment is imperative. This article discusses the concept of fluid responsiveness and reviews methods for assessing fluid responsiveness in critically ill patients.

Successful Treatment of a Critically Ill COVID-19 Patient Using Continuous Renal Replacement Therapy With Enhanced Cytokine Removal and Tocilizumab: A Case Report.

The COVID-19 pandemic has caused multiple deaths worldwide. Since no specific therapies are currently available, treatment for critically ill patients with COVID-19 is supportive. The most severe patients need sustained life support for recovery. We herein describe the course of a critically ill COVID-19 patient with multi-organ failure, including acute respiratory failure, acute kidney injury, and fulminant cytokine release syndrome (CRS), who required mechanical ventilation and extracorporeal membrane oxygenation support. This patient with a predicted high mortality risk was successfully managed with a careful strategy of oxygenation, uremic toxin removal, hemodynamic support, and most importantly, cytokine-targeted intervention for CRS, including cytokine/endotoxin removal, anti-cytokine therapy, and immune modulation. Comprehensive cytokine data, CRS parameters, and biochemical data of extracorporeal removal were provided to strengthen the rationale of this strategy. In this report, we demonstrate that timely combined hemoperfusion with cytokine adsorptive capacity and anti-cytokine therapy can successfully treat COVID-19 patients with fulminant CRS. It also highlights the importance of implementing cytokine-targeted therapy for severe COVID-19 guided by the precise measurement of disease activity.

Incidence and predictors of early and delayed renal function decline after aortic aneurysm repair in the Vascular Quality Initiative database.

BACKGROUND: Postoperative acute kidney injury (AKI) may complicate both open and endovascular aortic aneurysm repair (EVAR) and is associated with substantial morbidity, mortality, and health care expense. We aim to evaluate the incidence of postoperative AKI and factors associated with its occurrence and the effects of postoperative AKI on long-term renal function and mortality after open and EVAR in the Society for Vascular Surgery Vascular Quality Initiative registry. METHODS: Elective aneurysm cases were identified including thoracic endovascular aortic aneurysm repair (TEVAR) and complex endovascular aortic aneurysm repair (cEVAR), infrarenal endovascular repair (EVAR) and infrarenal open repair (OAR) from 2003 to 2019. The preoperative estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula and stratified based on chronic kidney disease (CKD) grades. Postoperative AKI was defined per the Vascular Quality Initiative definition as a creatinine increase of 0.5 mg/dL or if postoperative dialysis was required. Patients on preprocedural hemodialysis and those with previous renal transplant were excluded. Demographics and procedural factors were evaluated for predicting in-hospital postoperative AKI (all approaches) and at 9 to 21 months of long-term follow-up (EVAR only) using logistic regression modeling. RESULTS: We identified a total of 2813 cEVAR, 2995 TEVAR, 39,945 EVAR, and 8143 OAR patients. Of those, postoperative AKI occurred in 377 cEVAR (13.5%), 199 TEVAR (6.7%), 1099 EVAR (2.8%), and 1249 OAR (15.5%). Risk factors for postoperative AKI across all groups were worse preoperative eGFR, total number of blood transfusions, perioperative anemia, reinterventions, and postoperative respiratory complications. Additional procedure-specific risk factors of postoperative AKI were preoperative hemoglobin of less than 10 and contrast volume of 125 to 150 mL, hypertension, a low ejection fraction, and a history of percutaneous revascularization for EVAR; for both EVAR/cEVAR, renal artery coverage was a risk factor, whereas for OAR, male sex, non-White race, hypertension, suprarenal aortic cross-clamp, and increased renal ischemic time were risk factors. Among 8133 EVAR patients with long-term follow-up, a decrease in kidney function occurred in 56.7% of patients with postoperative AKI vs 19.9% without postoperative AKI (P < .001). The following risk factors were associated with a decrease in renal function at long-term follow-up: postoperative AKI, a preoperative eGFR of less than 90, and hypertension. A preoperative hemoglobin of greater than 12 was protective. Postoperative AKI was associated with significantly lower survival compared with no postoperative AKI across all procedures (log rank <0.001). CONCLUSIONS: Postoperative AKI occurs more often in patients with worse preoperative renal function, lower preoperative hemoglobin, and in open surgeries with inter-renal or suprarenal cross-clamping. Importantly, postoperative AKI is associated with increased mortality across all types of aortic repair. Given the long-term impact of postoperative AKI on outcomes for all aortic repairs and the limitations of current insensitive functional indices, there is a need to seek more sensitive indicators of decreases in early renal structural in this population.

Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury.

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.

Impact of CRRT in Patients with PARDS Treated with VV-ECMO.

The high mortality of pediatric acute respiratory distress syndrome (PARDS) is partly related to fluid overload. Extracorporeal membrane oxygenation (ECMO) is used to treat pediatric patients with severe PARDS, but can result in acute kidney injury (AKI) and worsening fluid overload. The objective of this study was to determine whether the addition of CRRT to ECMO in patients with PARDS is associated with increased mortality. METHODS: We conducted a retrospective 7-year study of patients with PARDS requiring ECMO and divided them into those requiring CRRT and those not requiring CRRT. We calculated severity of illness scores, the amount of blood products administered to both groups, and determined the impact of CRRT on mortality and morbidity. RESULTS: We found no significant difference in severity of illness scores except the vasoactive inotropic score (VIS, 45 ± 71 vs. 139 ± 251, p = 0.042), which was significantly elevated during the initiation and the first three days of ECMO. CRRT was associated with an increase in the use of blood products and noradrenaline (p < 0.01) without changing ECMO duration, length of PICU stay or mortality. CONCLUSION: The addition of CRRT to ECMO is associated with a greater consumption of blood products but no increase in mortality.