Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKI

The opportunity to make advances in the prevention and treatment of AKI has never been greater than it is today. Major advances have been made in the understanding of the biology of AKI, the design of clinical trials, and the use of diagnostic and prognostic biomarkers. These advances have been supplemented by the coordinated effort of societies, federal agencies, and industry, such that we are poised in the ensuing years to positively address the unrelenting harm that this disorder has created. Over the past decade, major advances have been made in understanding the pathophysiology of AKI, mainly through the study of small animal models. However, translating these findings to human AKI remains a barrier, which is typified by the absence of effective therapeutic agents. The purpose of the Acute Dialysis Quality Initiative (ADQI) XIII was to harmonize human and animal studies and determine what is known about potential therapeutic targets and what gaps in knowledge remain. A series of invited reviews will distill key concepts from this initiative that focus on different pathogenic features of AKI, including hemodynamics, immunity and inflammation, cellular and molecular pathways, progression, and regeneration and repair. This series will convey the status of our knowledge of the pathophysiology of human AKI and propose therapeutic targets for further investigation

Renal Hemodynamics in AKI: In Search of New Treatment Targets

Contains fulltext : 171381.pdf (publisher's version ) (Closed access)Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies

Potential use of biomarkers in acute kidney injury: Report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference

Over the last decade there has been considerable progress in the discovery and development of biomarkers of kidney disease, and several have now been evaluated in different clinical settings. Although there is a growing literature on the performance of various biomarkers in clinical studies, there is limited information on how these biomarkers would be utilized by clinicians to manage patients with acute kidney injury (AKI). Recognizing this gap in knowledge, we convened the 10th Acute Dialysis Quality Initiative meeting to review the literature on biomarkers in AKI and their application in clinical practice. We asked an international group of experts to assess four broad areas for biomarker utilization for AKI: risk assessment, diagnosis, and staging; differential diagnosis; prognosis and management; and novel physiological techniques including imaging. This article provides a summary of the key findings and recommendations of the group, to equip clinicians to effectively use biomarkers in AKI