Acute kidney injury: from clinical to molecular diagnosis
© The Author(s). 2016
Published: 7 July 2016
The original article was published in Critical Care 2016 20:41
The RIFLE classification was introduced in 2004 to describe the presence of acute kidney injury (AKI) and to define its clinical stage, based upon the serum creatinine level and urine output. The same criteria, although slightly modified, are used in the other scoring systems AKIN and KDIGO. Mortality and morbidity remain high in AKI, suggesting that current diagnostic methods are suboptimal, poorly accurate, and often timely inadequate in detecting the presence of early kidney injury. Conversely, a growing body of evidence indicates that new AKI biomarkers can be used to both rule out AKI and to assess high-risk conditions or the presence of subclinical forms. Neutrophil gelatinase-associated lipocalin or cell cycle arrest biomarkers seem to be sensitive and specific enough to be used in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction. Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring may improve prevention and protection from organ damage and help to identify patients at risk, allowing individualized therapy. In this view, we may say that AKI diagnosis has finally moved from clinical to molecular level with potential benefits for the patients because similar progress has been shown in other disciplines.
New biomarkers can detect a risk of AKI or subclinical kidney damage earlier, allowing development of a new conceptual model for AKI with a continuum from initial kidney stress and early injury to advanced kidney damage and/or failure. The acute phase has also been called “Kidney Attack”  while the subsequent phases in the time window of 90 days are described as acute kidney disease (AKD). Full recovery or maladaptive repair with progression towards chronic kidney disease (CKD) is also a pathway described in the model. At each point of the continuum, biomarkers may play a role in clarifying mechanisms and clinical evolution of AKI. Studies on biomarkers have described their positive and negative predicting value for the presence and severity of the syndrome, site of damage, need for renal replacement therapy (RRT), and recovery or progression towards CKD . Unfortunately, these studies present a high degree of heterogeneity, and meaningful conclusions are only obtained in specific populations.
Zhang et al.  conducted a meta-analysis focusing on the value of neutrophil gelatinase-associated lipocalin (NGAL) to predict AKI and clinical outcomes such as need for RRT and mortality in a specific subset of patients with sepsis. Fifteen studies were included in the analysis, confirming high-pooled sensitivity and specificity values for both plasma and urine NGAL. The authors concluded that NGAL is not only a good predictor of AKI but is also an efficient test to predict the need for RRT and mortality in septic patients.
Some questions remain open. Do we have discrete quantitative values correlated with level of damage/dysfunction or outcome? Can we diagnose AKI only in the basis of these molecular markers even in the absence of abnormal urine output or SCr? Does the cost/benefit ratio justify the use of these expensive biomarkers in critically ill patients? Are we ready to use these biomarkers routinely?
Not only can biomarkers be used to establish the presence and the severity of AKI, but they may also be used to identify a status of kidney stress or an increased susceptibility to insults. In such conditions, they may trigger early preventive and protective measures well before clinical AKI becomes manifest according to the KDIGO criteria .
In conclusion, some of the key questions about biomarkers begin to find concrete answers . The additional value of making an early and accurate diagnosis of AKI is gaining evidence and the role of biomarkers is increasing. Discrete quantitative values correlating with the level of damage/dysfunction are available and they will foster further studies of validation and support. Beyond the detection of increased risk and kidney stress conditions, today we can make a diagnosis of AKI based solely on molecular criteria even in the presence of normal urine output or SCr. The concept is mirroring what happened in the acute coronary syndrome in the absence of ST elevation on the EKG, where troponin made possible the diagnosis of non-ST elevation myocardial infarction. . All of these considerations may suggest a remarkable cost/benefit advantage justifying the use of expensive biomarkers in specific populations. Thus, we will probably soon be ready to use AKI biomarkers routinely for the benefit of the patients and the strategic evolution of our healthcare plans.
ADQI, Acute Disease Quality Initiative; AKD, acute kidney disease; AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; CKD, chronic kidney disease; EKG, electrocardiogram; KDIGO, Kidney Disease Global Outcome Initiative; NGAL, neutrophil gelatinase-associated lipocalin; RIFLE, Risk, Injury, Failure, Loss and End Stage Kidney Disease; RRT, renal replacement therapy; SCr, serum creatinine
CR drafted the manuscript. The author read and approved the final manuscript.
CR received speakers and consultation honoraria from ASAHI, Toray, FMC, Baxter, Astute, Bioporto, ESTOR, GE, and ABBVIE in the last 2 years. The author declares that he has no other competing interests.
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