Zarbock, Alexander

Scientific evidence regarding AKI and acute kidney care has advanced in recent years. However, a knowledge gap remains on the implementation of these evidence-based practices (EBPs) into clinical care. Implementation science (IS) is focused on ensuring that this knowledge is translated in an effective, efficient and sustainable fashion. Objectives: 1) Define the current status of IS; 2) Define a roadmap for accelerating IS with a focus on patient/care partner advocacy, digital tool application, social determinants of health, and resource-limited settings; and 3) Develop a robust and broad research agenda incorporating IS methodology into the programs. Evidence Review: ADQI XXXV was conducted through a modified Delphi process with virtual meetings preceding an in-person meeting. Five workgroups were determined a priori to focus on 1) IS definitions and methods applicable to AKI and acute kidney care; 2) IS literature in AKI and acute kidney care; 3) Innovations in IS to accelerate the adoption, adherence to, and sustainment of EBPs in AKI and acute kidney care; 4) IS methods in resource-limited settings; and 5) Recommendations to identify and evaluate EBPs that are ready for implementation or de-implementation. Prior to the in-person meeting, each workgroup met virtually to review the literature and develop framework questions to address their objectives. During the two-day in person meeting, through iterative discussions, questions and supporting statements were finalized. These questions and statements were agreed upon through voting to achieve consensus, defined as agreement of ≥80%. Conclusions and Relevance: We report a structured multidisciplinary consensus for defining the role of IS in AKI and acute kidney care. Future programs should address these consensus questions and apply these statements along with IS methodology in the translation of science into clinical practice and the implementation/de-implementation of EBPs in clinical care.

ABSTRACT Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators.

Abstract Background The assessment of kidney function and detection of acute kidney injury (AKI) remain cumbersome. On the one hand, because of limited accuracy of established tests: The most widely used methods are creatinine based, which lack in sensitivity, as creatinine is not purely filtrated by the kidney and rises relatively late after onset of AKI. On the other hand, because of labor-intensiveness: Gold standard inulin clearance and comparable methods involve intravenous compound infusion, blood sampling at several time points, and have error-sensitive determination methods. In recent years, several biomarkers have been put forward (e.g., NGAL, KIM-1, TIMP-2*IGFBP-7), but clinical implementation is limited up to now. Content Proenkephalin (PENK) represents a new candidate to determine kidney function. This peptide is cleaved from the precursor peptide preproenkephalin A alongside enkephalins (endogenous opioids) and is filtrated in the glomerulus. PENK plasma concentration appears to accurately represent glomerular filtration rate in patients diagnosed with sepsis or cardiac diseases. Moreover, increased PENK concentration is found to be associated with longer-term outcome concerning AKI and cardiac diseases. Lastly, the predominant receptor of enkephalins, the δ-opioid receptor, is expressed with the highest density in the kidney, suggesting that enkephalins could also exert a direct effect on kidney function. Summary In this review, we present an overview of enkephalins and the assessment of kidney function using this possible new functional biomarker PENK and compare it with established and novel biomarkers.

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo ( p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo ( p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo ( p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease.