IntroductionAcute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.MethodsWe performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.ResultsModerate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.ConclusionsTwo novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.Trial registrationClinicalTrials.gov number NCT01209169.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

IMPORTANCE In the last decade, new biomarkers for acute kidney injury (AKI) have been identified and studied in clinical trials. Guidance is needed regarding how best to incorporate them into clinical practice. OBJECTIVE To develop recommendations on AKI biomarkers based on existing data and expert consensus for practicing clinicians and researchers. EVIDENCE REVIEW At the 23rd Acute Disease Quality Initiative meeting, a meeting of 23 international experts in critical care, nephrology, and related specialties, the panel focused on 4 broad areas, as follows: (1) AKI risk assessment; (2) AKI prediction and prevention; (3) AKI diagnosis, etiology, and management; and (4) AKI progression and kidney recovery. A literature search revealed more than 65 000 articles published between 1965 and May 2019. In a modified Delphi process, recommendations and consensus statements were developed based on existing data, with 90% agreement among panel members required for final adoption. Recommendations were graded using the Grading of Recommendations, Assessment, Development and Evaluations system. FINDINGS The panel developed 11 consensus statements for biomarker use and 14 research recommendations. The key suggestions were that a combination of damage and functional biomarkers, along with clinical information, be used to identify high-risk patient groups, improve the diagnostic accuracy of AKI, improve processes of care, and assist the management of AKI. CONCLUSIONS AND RELEVANCE Current evidence from clinical studies supports the use of new biomarkers in prevention and management of AKI. Substantial gaps in knowledge remain, and more research is necessary.

Revimmune, NIH National Institute of General Medical Sciences GM44118.

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Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis.

I n 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). 1 Since then, new evidence has emerged that has important implications for clinical practice. Large epidemiology studies and risk profiles for AKI have become available in adults and children, such as the AKI-Epidemiologic Prospective Investigation (AKI-EPI) study, 2 the 0by25 Initiative, 3 the Southeast Asia-AKI (SEA-AKI) study, 4 and the Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) 5 and Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) 6 studies. The effectiveness of the KDIGO recommendations in preventing AKI has been confirmed in small single-center randomized controlled trials (RCTs), such as the Prevention of AKI (PrevAKI) 7 and the

The NST (New Solar Telescope), a 1.6 m clear aperture, off-axis telescope, is in its commissioning phase at Big Bear Solar Observatory (BBSO). It will be the most capable, largest aperture solar telescope in the US until the 4 m ATST (Advanced Technology Solar Telescope) comes on-line late in the next decade. The NST will be outfitted with state-of-the-art scientific instruments at the Nasmyth focus on the telescope floor and in the Coudé Lab beneath the telescope. At the Nasmyth focus, several filtergraphs already in routine operation have offered high spatial resolution photometry in TiO 706 nm, Hα 656 nm, G-band 430 nm and the near infrared (NIR), with the aid of a correlation tracker and image reconstruction system. Also, a Cryogenic Infrared Spectrograph (CYRA) is being developed to supply high signal-to-noise-ratio spectrometry and polarimetry spanning 1.0 to 5.0 μm. The Coudé Lab instrumentation will include Adaptive Optics (AO), InfraRed Imaging Magnetograph (IRIM), Visible Imaging Magnetograph (VIM), and Fast Imaging Solar Spectrograph (FISS). A 308 sub-aperture (349-actuator deformable mirror) AO system will enable nearly diffraction limited observations over the NST's principal operating wavelengths from 0.4 μm through 1.7 μm. IRIM and VIM are Fabry-Pérot based narrow-band tunable filters, which provide high resolution two-dimensional spectroscopic and polarimetric imaging in the NIR and visible respectively. FISS is a collaboration between BBSO and Seoul National University focussing on chromosphere dynamics. This paper reports the up-to-date progress on these instruments including an overview of each instrument and details of the current state of design, integration, calibration and setup/testing on the NST.