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2010, Anesthesiology
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.
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.
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 in medicine, 2014
Clinical Kidney Journal, 2012
Acute kidney injury (AKI) is strongly associated with increased morbidity and mortality in critically ill patients. Efforts to change its clinical course have failed because clinically available therapeutic measures are currently lacking, and early detection is impossible with serum creatinine (SCr). The demand for earlier markers has prompted the discovery of several candidates to serve this purpose. In this paper, we review available biomarker studies on the early predictive performance in developing AKI in adult critically ill patients. We make an effort to present the results from the perspective of possible clinical utility.
Clinical Chemistry, 2014
American journal of physiology. Renal physiology, 2016
No new biomarker of Acute Kidney Injury (AKI) has entered routine clinical practice after a decade of promise, although L-FABP, NGAL, and the combination of TIMP2 and IGFBY-7 are approved for use in some jurisdictions. Acceptance of creatinine as a surrogate of not just GFR but also renal injury, changes in nephrologist work loads, failure to establish the added value of each biomarker to current clinical variables across multiple clinical settings, the lack of treatment options, and simply an insufficient passage of time, have all contributed to the lack of progress. Future studies should establish reference intervals for biomarkers, associate biomarkers with meaningful clinical outcomes including mortality and development of Chronic Kidney Disease, and assess the added value to clinical models. The real value of biomarkers will be determined with intervention trials that use an elevated biomarker to triage to treatment. Ideally, such treatments will be linked directly to the physi...
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.
Current Opinion in Pediatrics, 2011
Purpose of review-Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which depends on serum creatinine, which is a delayed and unreliable indicator of AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The current status of the most promising of these novel AKI biomarkers, including NGAL, KIM-1, L-FABP and IL-18, is reviewed. Recent findings-In particular, NGAL is emerging as an excellent biomarker in the urine and plasma, for the early prediction of AKI, for monitoring clinical trials in AKI, and for the prognosis of AKI in several common clinical scenarios. However, biomarker combinations may be required to improve our ability to predict AKI and its outcomes in a context-specific manner. Summary-It is vital that additional large future studies demonstrate (a) the association between biomarkers and hard clinical outcomes independent of serum creatinine concentrations, and (b) that randomization to a treatment for AKI based on high biomarker levels results in an improvement in clinical outcomes.
2011
Urologists are integrally involved in the management of acute kidney injury (AKI), which is common after renal surgery or secondary to postrenal (obstructive) etiologies. The measurement of serum creatinine is a suboptimal indicator of AKI because it lags behind acute changes in renal function. Recent advances indicate that serum/urine biomarkers will prove useful for early detection of AKI, analogous to the use of cardiac enzymes for acute myocardial infarction. These serum/urine markers may guide future therapy, facilitate research efforts to reduce the severity of AKI, such as after partial nephrectomy, and allow for more accurate prognostication for patients with AKI. UROLOGY 77: 5-11, 2011.
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.
The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists
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.
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.
Biomedical Reviews, 2020
Acute kidney injury (AKI) is a common public health problem and has a significant impact on cardiovascular disease, mortality and increased hospital costs. Also, AKI can progress to chronic kidney disease (CKD). Therefore, early diagnosis is very important for AKI. Serum creatinine (SCr) is a well-known biomarker in the diagnosis of AKI. However, changes in SCr levels are insufficient in early diagnosis so, new biomarkers are needed. Because of that, the search for biomarkers for the early detection of AKI is an ongoing process. In recent years, early diagnosis, prognostic and predictive biomarkers have been discovered to replace or support SCr in the diagnosis of AKI. New biomarkers can help early diagnosis and effective management of AKI. Since there are many biomarkers, when and under which condition these biomarkers should be used cause confusion. In this review, we aimed to construct and ease to use classification of these AKI biomarkers and summarize the current literature. We have divided the biomarkers into two main categories: renal and non-renal origin. Then, we have classified the biomarkers of renal origin as glomerular, tubular and unknown renal site. We have also described the clinical use of these biomarkers for diagnosis and prognosis.
AKI is an increasingly common disorder that is strongly linked to short-and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.
Bangladesh Journal of Child Health, 2014
ADQI Consensus on AKI Biomarkers and Cardiorenal Syndromes, 2013
Detection of acute kidney injury is undergoing a dynamic revolution of biomarker technology allowing greater, earlier, and more accurate determination of diagnosis, prognosis, and with powerful implication for management. Biomarkers can be broadly considered as any measurable biologic entity or process that allows differentiation between normal function and injury or disease. The ADQI (Acute Dialysis Quality Initiative) had its Ninth Consensus Conference dedicated to synthesis and formulation of the existing literature on biomarkers for the detection of acute kidney injury in a variety of settings. In the papers that accompany this summary, ADQI workgroups fully develop key concepts from a summary of the literature in the domains of early diagnosis, differential diagnosis, prognosis and management, and concurrent physiologic and imaging measures.
Critical Care, 2012
The recognition that acute kidney injury (AKI) is a signifi cant independent risk factor for morbidity and mortality has resulted in a substantial number of publications over the past 5 years or more. In no small part these have, to a degree, highlighted the inadequacy of conventional markers of renal insuffi ciency in the acute setting. Much eff ort has been invested in the identifi cation of early, specifi c AKI markers in order to aid early diagnosis of AKI and hopefully improve outcome. The search for a 'biomarker' of AKI has seen early promise replaced by a degree of pessimism due to the lack of a clear candidate molecule and variability of results. We outline the major studies described to date as well as discuss potential reasons for the discrepancies observed and suggest that evolution of the fi eld may result in success with ultimately an improvement in patient outcomes.
Best Practice & Research Clinical Anaesthesiology, 2017
biomarkers biomarkers of function biomarkers of damage risk diagnosis prognosis Acute kidney injury is common in critically ill patients and portends a significant impact on mortality, progressive chronic kidney disease, and cardiovascular disease and mortality. Though most physicians alter therapy depending on changes in serum creatinine, this often represents delayed intervention. Various AKI biomarkers have been discovered and validated to improve timely detection, differentiation and stratification into risk groups for progressive renal decline, need for renal replacement therapy or death. This chapter will review AKI biomarkers validated over the past decade. We also describe the clinical performance of the biomarkers. We suggest that using AKI biomarkers to complement serum creatinine (or cystatin C) and urine output will better integrate patient care through earlier recognition and clinical outcome prediction after AKI.
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.
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