Forni, Lui G.

Key Points Pooled discrimination metrics were acceptable (area under the receiver operating characteristic curve >0.70) for all AKI risk classification categories in both internal and external validation. Better performance was observed in most recently published studies and those with a low or unclear risk of bias. Significant heterogeneity in patient populations, definitions, clinical predictors, and methods limit implementation in real-world clinical scenarios. Background Artificial intelligence through machine learning models seems to provide accurate and precise AKI risk classification in some clinical settings, but their performance and implementation in real-world settings has not been established. Methods PubMed, Excerpta Medica (EMBASE) database, Web of Science, and Scopus were searched until August 2023. Articles reporting on externally validated models for prediction of AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric patients were searched using text words related to AKI, artificial intelligence, and machine learning. Two independent reviewers screened article titles, abstracts, and full texts. Areas under the receiver operating characteristic curves (AUCs) were used to compare model discrimination and pooled using a random-effects model. Results Of the 4816 articles initially identified and screened, 95 were included, representing 3.8 million admissions. The Kidney Disease Improving Global Outcomes (KDIGO)-AKI criteria were most frequently used to define AKI (72%). We identified 302 models, with the most common being logistic regression (37%), neural networks (10%), random forest (9%), and eXtreme gradient boosting (9%). The most frequently reported predictors of hospitalized incident AKI were age, sex, diabetes, serum creatinine, and hemoglobin. The pooled AUCs for AKI onset were 0.82 (95% confidence interval, 0.80 to 0.84) and 0.78 (95% confidence interval, 0.76 to 0.80) for internal and external validation, respectively. Pooled AUCs across multiple clinical settings, AKI severities, and post-AKI complications ranged from 0.78 to 0.87 for internal validation and 0.73 to 0.84 for external validation. Although data were limited, results in the pediatric population aligned with those observed in adults. Between-study heterogeneity was high for all outcomes (I 2 >90%), and most studies presented high risk of bias (86%) according to the Prediction Model Risk of Bias Assessment Tool. Conclusions Most externally validated models performed well in predicting AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric populations. However, heterogeneity in clinical settings, study populations, and predictors limits their generalizability and implementation at the bedside.

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.

Objectives: Decreased urine output and/or increased serum creatinine may herald the development of acute kidney injury or reflect normal physiology. In this secondary analysis of the Sapphire study, we examined biomarkers of cell cycle arrest in the settings of oliguria and/or azotemia to improve risk assessment when used with conventional indices in predicting severe acute kidney injury (Kidney Disease: Improving Global Outcomes 3 defined by the need for renal replacement therapy or changes in urine output, serum creatinine or both) or death. Design: Prospective, international, Sapphire study. Setting: Academic Medical Center. Patients: Patients without acute kidney injury Kidney Disease: Improving Global Outcomes stage 2 or 3. Interventions: None. Measurements and Main Results: The primary endpoint being development of severe acute kidney injury or death within 1 week. Secondary analysis examined the relationship between tissue inhibitor of metalloproteinases-2 ([TIMP-2]) and insulin growth factor binding protein 7 ([IGFBP7]) and 9-month death or dialysis conditioned on progression to stage 2–3 acute kidney injury within 1 week. Seventy-nine patients reached the primary endpoint and were more likely to be surgical, with higher nonrenal Acute Physiology and Chronic Health Evaluation III scores and more chronic kidney disease. Stage 1 urine output, serum creatinine, and urinary [TIMP-2]•[IGFBP7] greater than 2.0 were all predictive of progression to the primary endpoint independent from nonrenal Acute Physiology and Chronic Health Evaluation III score. Combinations of predictors increased the hazard ratios considerably (from 2.17 to 4.14 to 10.05, respectively). In the presence of acute kidney injury (stage 1), [TIMP-2]•[IGFBP7] greater than 2.0 leads to an increased risk of death or dialysis at 9 months even in the absence of progression of acute kidney injury (stage 2–3) within 7 days. Conclusions: Cell cycle arrest biomarkers, TIMP-2 and IGFBP7, improve risk stratification for severe outcomes in patients with stage 1 acute kidney injury by urine output, serum creatinine or both, with risk increasing with each acute kidney injury indicator. Longer term outcomes demonstrate that the associated risks of a [TIMP-2]•[IGFBP7] greater than 2.0 is equivalent to acute kidney injury progression even where no progression from stage 1 acute kidney injury is observed.

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.

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.