Mehta, Ravindra L.

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 Pregnancy-associated acute kidney injury (PrAKI) remains a major contributor to maternal and foetal morbidity worldwide, with an estimated incidence of 40–100 per 10 000 pregnancies. PrAKI is substantially more prevalent in low- and middle-income countries. Unlike acute kidney injury episodes unrelated to pregnancy, PrAKI arises in a unique physiological context characterized by haemodynamic adaptation, immune tolerance, hormonal modulation, and the presence of the foetal–placental unit. These pregnancy-specific factors alter renal reserve, endothelial stability, and inflammatory responsiveness. The pathogenesis of PrAKI is multifactorial. Haemodynamic vasodilation and increased glomerular filtration rates during pregnancy reduce renal functional reserve, rendering the kidney vulnerable to hypovolemia and sepsis. Placental ischaemia drives the release of antiangiogenic factors, particularly soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, causing systemic endothelial dysfunction and glomerular endotheliosis. Disruption of immune tolerance and complement regulation further contributes to microangiopathy and autoimmune-mediated renal injury. Structural urinary tract changes, metabolic stressors, and maternal comorbidities amplify susceptibility. Beyond the index event, PrAKI has lasting consequences. Maladaptive renal repair promotes chronic kidney disease and long-term cardiovascular risk, while foetal exposure to uremic toxins and placental dysfunction contribute to intrauterine growth restriction, prematurity, and reduced nephron mass with lifelong cardio-renal implications. Understanding the pathophysiology of PrAKI, particularly endothelial, immunologic, and placental interactions, has direct diagnostic and therapeutic implications, including the use of angiogenic biomarkers and targeted haemodynamic strategies. Future research must prioritize molecular predictors, global registries, and mechanistic studies to reduce intergenerational kidney and cardiovascular disease.

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.

Importance Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

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.