RIFLE is alive: long live RIFLE

Diagnosis and classification of acute kidney injury was addressed systematically only 8 years ago when the classification called RIFLE (acronym of Risk, Injury, Failure, Loss of function and End stage Kidney disease describing progressive severity of renal damage) was created. Since then, several studies have tried to apply, validate, criticize and modify this initial scheme: as a matter of fact, RIFLE is today one of the most appreciated and utilized medical classification systems worldwide. After an initial period of epidemiological research, it is acceptable to apply it now at the bedside, following both urine output and creatinine criteria, with the purpose of routinely monitoring renal function of critically ill patients.

RIFLE criteria with epidemiological studies on AKI [2]. It has to be noted that a 'defi nition' should not be confounded with the concept of 'aetiological diagnosis': RIFLE criteria were not born to identify the cause of AKI but only to identify it in a standardized way. Consequently, a renewed interest in AKI diagnosis, prevention and treatment was raised by this huge amount of standardized information [3]: today, awareness of actual AKI incidence and of its lethal eff ects (even after milder forms of renal impairment) in several clinical settings has dramatically increased and some centers have already implemented RIFLE score in their databases and medical records [4]. Th e other side of the coin was that, even if sometimes unintentionally, each study tended to slightly modify the original RIFLE defi nition in order to best adapt it to its research [5]. To cite just a few, in retrospective epi demiological studies, urine output (UO) criteria have been discarded because this kind of data is not easily achievable in databases [5]. In other cases, baseline creatinine (essential in RIFLE scoring) has been argued about, estimated or not evaluated because it is not available for all patients [5]. Some authors have fi nally verifi ed the RIFLE criteria on large cohorts of critically ill patients for very short periods of time, such as the fi rst 24 hours after ICU admission [5]. It must be acknowledged that this variation may have signifi cantly aff ected fi ndings on AKI prevalence, incidence and prognosis.

The present
In the previous issue of Critical Care Wlodzimirow and coworkers [6] show in a prospective observational study how RIFLE criteria should be correctly used. Th ey substantially simulated routine use of RIFLE classifi cation with UO criteria (RIFLE serum creatinine (sCr)+UO) and without UO criteria (RIFLE sCr) for a whole week after ICU admission. Th e authors also included patients without known pre-ICU creatinine and estimated it, as suggested by RIFLE, with the Modifi cation of Diet in Renal Disease formula [1]. According to their fi ndings, the use of RIFLE without the urine criteria signifi cantly underscores the incidence and grade of AKI, signifi cantly delays the diagnosis of AKI and underestimates mortality rates. Remarkably, the accurate analysis by Wlodzimirow and colleagues reveals that AKI diagnosis during the fi rst Abstract Diagnosis and classifi cation of acute kidney injury was addressed systematically only 8 years ago when the classifi cation called RIFLE (acronym of Risk, Injury, Failure, Loss of function and End stage Kidney disease describing progressive severity of renal damage) was created. Since then, several studies have tried to apply, validate, criticize and modify this initial scheme: as a matter of fact, RIFLE is today one of the most appreciated and utilized medical classifi cation systems worldwide. After an initial period of epidemiological research, it is acceptable to apply it now at the bedside, following both urine output and creatinine criteria, with the purpose of routinely monitoring renal function of critically ill patients.
week of ICU admission was doubled by RIFLE sCr+UO, probably due to transient periods of oliguria not followed by increases in creatinine level. Interestingly, Prowle and coauthors [7], driven by a similar idea, recently concluded that oliguria (<0.5 ml/kg/h) is a modest predictor of subse quent creatinine increase, especially when lasting for shorter periods of time (<12 hours). Th is aspect should be taken into account in clinical practice and, obviously, AKI should not be classifi ed after 30 minutes of anuria: as a matter of fact, the UO-Risk class of RIFLE needs at least 6 hours of oliguria before the criterion is reached. However, UO is by far one of the earliest clinical signs of acute renal impairment. Furthermore, we know that subclinical AKI, either identifi ed by pathological levels of early biomarkers (such as neutrophil gelatinaseassociated lipocalin) [8], or by transient azotemia (defi ned as rapidly recovering AKI with return to no-AKI RIFLE class within 72 hours of onset) [9] is indeed associated with poor outcomes. On the other hand, creatinine alone may underscore the severity of AKI, due to its delayed increase in the setting of rapidly evolving AKI, especially in patients with fl uid overload and hemodilution [10]. Alertness to milder forms of AKI, those with the potential of worsening and that should be targeted by specifi c treatment, is one of the most important goals of the RIFLE classifi cation.

Conclusion: the future?
RIFLE is an imperfect, questionable, conventional, practical defi nition. Th e original aim of its creators was not to predict mortality or to associate it with any hard clinical outcome, but to fi nd a common language on AKI diagnosis. Still, clinical validation was performed and it achieved satisfactory results. New criteria [11,12] have been proposed as substitutes of RIFLE in an attempt to improve the sensitivity and specifi city of the AKI identifi cation: they apparently failed to achieve signifi cant results [5]. It should be considered whether a fi ne-tuning of the original RIFLE criteria might have worked better. Moreover, as an exclusively personal opinion, RIFLE customizations and new classifi cations might have induced confusion and uncertainty in readers and clinicians, those originally intended to be the main users of such criteria. It must be remembered that the acute respiratory distress syndrome defi nition, born under the same rationale as RIFLE (but many years earlier), has been recently modifi ed after about two decades of worldwide application [13,14].
In conclusion, the time has come to apply RIFLE clinically, at the bedside, applying both UO and creatinine criteria [9], with the purpose of longitudinally monitoring the renal condition of critically ill patients.
Th e next step of RIFLE will be to understand if it is actually possible to standardize AKI prevention strategies or therapeutic approaches to the diff erent severity classes: early attempts have already been performed with success [15].
Abbreviations AKI, acute kidney injury; RIFLE, Risk, Injury, Failure, Loss of function and End stage Kidney disease; sCr, serum creatinine; UO, urine output.