Implementation of Novel Biomarkers in the Diagnosis, Prognosis, and Management of Acute Kidney Injury: Executive Summary from the Tenth Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) (original) (raw)
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Kidney International, 2014
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. While 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 (ADQI) 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. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Biomarkers of acute kidney injury
Jornal brasileiro de nefrologia : ʹorgão oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Acute kidney injury (AKI) is a common condition with a high risk of death. The standard metrics used to define and monitor the progression of AKI, such as serum creatinine and blood urea nitrogen levels, are insensitive, nonspecific, and change significantly only after significant kidney injury and then with a substantial time delay. This delay in diagnosis not only prevents timely patient management decisions, including administration of putative therapeutic agents, but also significantly affects the preclinical evaluation of toxicity thereby allowing potentially nephrotoxic drug candidates to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. Studies to establish effective therapies for AKI will be greatly facilitated by two factors: (a) development of sensitive, specific, and reliable biomarkers for early diagnosis/prognosis of AKI in preclinical and clinical studies, and (b) development and validation of high-throughput innovative technologies that allow rapid multiplexed detection of multiple markers at the bedside.
Using biomarkers for acute kidney injury: barriers and solutions
Nephron. Clinical practice, 2014
The clinical implementation of urinary and plasma renal injury biomarkers has been hampered by the variability associated with nonstandardized commercially available biomarker assays, uncertainty and variations in patient selection criteria, and the absence of context-specific cutoffs for biomarker concentrations. These limitations are increased by comparison with serum creatinine to define acute kidney injury. The critical problem affecting biomarker performance is patient heterogeneity involving the cause, context (including comorbidity and baseline renal function), and timing of the injury. We suggest strategies for stratifying subjects to provide appropriate context, and illustrate a creatinine-independent method for defining thresholds for biomarker concentrations in these contexts which utilizes the same sensitivity for the clinical outcomes of dialysis or death. Large multicenter cohort studies are needed to validate the proposed cutoffs.
New Biomarkers for the Quick Detection of Acute Kidney Injury
ISRN Nephrology, 2013
Acute kidney injury (AKI) is a common and strong problem in the diagnosis of which based on measurement of BUN and serum creatinine. These traditional methods are not sensitive and specific for the diagnosis of AKI. AKI is associated with increased morbidity and mortality in critically ill patients and a quick detection is impossible with BUN and serum creatinine. A number of serum and urinary proteins have been identified that may messenger AKI prior to a rise in BUN and serum creatinine. New biomarkers of AKI, including NGAL, KIM-1, cystatin-C, IL-18, and L-FABP, are more favourable tests than creatinine which have been identified and studied in several experimental and clinical training. This paper will discuss some of these new biomarkers and their potential as useful signs of AKI. We searched the literature using PubMed and MEDLINE with acute kidney injury, urine, and serum new biomarkers and the articles were selected only from publication types in English.
Acute Kidney Injury Biomarkers - Needs, Present Status, and Future Promise
Nephrology self-assessment program : NephSAP, 2006
In the last decade, great progress has been made in dissecting the molecular mechanisms of Acute Kidney Injury (AKI; Also known as Acute Renal Failure, ARF)); however, translation of these findings to therapeutics of clinical utility has lagged. Development of therapeutics for AKI is has been slow and garnered limited industry interest because AKI is poorly characterized and difficult to diagnose early. Additional challenges include an inability to predict severity, measure progression, or response to therapy, all of which add complexity and risk to clinical trials. A standard definition of AKI is being developed, which will facilitate progress greatly. However, the over-reliance on serum creatinine as a marker of renal function and injury and the absence of additional disease markers has hampered clinical trials for AKI. Serum creatinine in AKI has poor sensitivity and specificity; patients are not in steady state, hence serum creatinine lags behind both renal injury and renal recovery. Conventional urine markers (casts, fractional excretion of sodium) are non-specific and insensitive. Reliance on traditional markers slows recognition of AKI and hence delays nephrologic consultation and discontinuation of nephrotoxic agents, and complicates drug development.
Biomarkers for the diagnosis of acute kidney injury
Current Opinion in Nephrology and Hypertension, 2007
tests for AKI include serum creatinine (SCr) and blood urea nitrogen (BUN), two biomarkers that were identified and incorporated into clinical practice several decades ago. It is now widely appreciated that SCr and BUN are suboptimal markers for AKI, and that more sensitive, specific, and early biomarkers are needed. This review sets out to cover recent developments in the field of AKI biomarker validation in clinical studies. Injury versus Failure: Towards a Troponin for the Kidney The new term 'acute kidney injury' instead of 'acute renal failure'-by its replacement of the word 'injury' for 'failure'-hints towards a paradigm shift in nephrology. The diagnosis of 'failure' refers to the kidney's inability to perform one of its major functions, namely glomerular filtration. The diagnosis of glomerular filtration failure is made only after endogenous filtration markers (BUN or SCr) have accumulated in the blood, typically hours or even days after an inciting event. The diagnosis of 'injury', by contrast, does not presuppose a reduction in glomerular filtration. Newer biomarkers are needed to identify correlates of cellular (typically tubular) injury, which may be present well before or in the absence of a reduction in GFR. The analogy to cardiology may be instructive: clinicians diagnosing acute myocardial infarction do not wait until a reduction in cardiac output, but rather make the diagnosis of myocardial injury on the basis of elevations of tissuespecific biomarkers in the serum. The biological response of kidney tissue to ischemic or nephrotoxic injury may be utilized as early indicators of
Early detection of acute kidney injury: Emerging new biomarkers (Review Article)
Nephrology, 2008
Acute kidney injury (AKI) has recently become the preferred term to describe the syndrome of acute renal failure (ARF) with 'failure' or 'ARF' restricted to patients who have AKI and need renal replacement therapy. 1 This allows capture of the broader clinical spectrum of modest reductions in creatinine, which are themselves known to be associated with major increases in both short-and long-term mortality risk. 2-5 It is hoped that this change in nomenclature will facilitate an expansion of our understanding of the underlying pathophysiology and also facilitate definitions of AKI, which allow comparisons among clinical trials of patients with similar duration and severity of illness. This review will cover the need for early detection of AKI and the role of urinary and plasma biomarkers, including enzymuria. The primary message is that use of existing criteria to diagnose AKI, namely elevation of the serum creatinine with or without oliguria, results in identification that is too late to allow successful intervention. New biomarkers are essential to change the dire prognosis of this common condition.
Biomarkers in acute kidney injury: Evidence or paradigm?
Nefrología, 2016
Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.
JAMA Network Open
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.