From acute renal failure to acute kidney injury: Emerging concepts*

Acute renal failure (ARF) remains a medical problem of daunting outcome: even the best centers typically report mortalities of 50–80% now in the 21 century. Recent epidemiologic studies demonstrate the wide variation in etiologies and risk factors (1–5), describe the increased mortality associated with this disease particularly when dialysis is required (1, 3, 6, 7), and suggest a relationship to the subsequent development of chronic kidney disease and progression to dialysis dependency (1, 6–8). Unfortunately, ARF is often unrecognized as definitions for the disease range from quantitative and qualitative alterations in serum creatinine to alterations in urine output and dialysis requirement (1, 9–12). The lack of a universally recognized definition of ARF has posed a significant limitation contributing to the lack of clinical success (13). Recognizing the need for uniform standards, the Acute Dialysis Quality Initiative (ADQI) group in 2002 proposed consensus recommendations of the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria for the definition and staging of ARF (14). The wide interest sparked by the publication of these criteria demonstrated the additional need for multidisciplinary collaborative efforts for clinical and translational research in this area. Consequently, the Acute Kidney Injury Network (AKIN) was formed to facilitate the development and execution of initiatives to ensure the best outcomes for patients with acute kidney injury (15). As an initial step the AKIN group proposed the term acute kidney injury (AKI) to reflect the entire spectrum of ARF and developed interim diagnostic and staging criteria for AKI. The diagnostic criteria require a 0.3 mg/dL or 50% change in serum creatinine from baseline or a reduction on urine output of 0.5 ml/kg/hr over a 6-hr interval, within a 48-hr period, following adequate volume resuscitation. These criteria were based on accumulating evidence that even small alterations in serum creatinine are associated with severe consequences (14, 16–21) and the RIFLE stage correlated with adverse events (22). The AKIN staging system additionally characterizes the severity of renal dysfunction at diagnosis and different time points during the course of the disease (15). Validation of these concepts is now provided by the study of Barrantes et al. in this issue (23). In a consecutive cohort of 471 patients admitted to a general medical intensive care unit (ICU) in a community hospital, 120 patients (25.4%) developed AKI based on the AKIN serum creatinine and urine output criteria despite a fluid challenge of at least 500 ml saline over one hour. An additional 90 patients met similar criteria, but lacked information on a fluid challenge. Dialysis was required only in 18 (15%) AKI patients; however, there was a three-fold increase in hospital mortality and a two-fold increase in hospital length of stay. Various permutations of the AKIN definitions (absolute or relative change of serum creatinine or change in urine output) were each independently associated with a worse outcome with the strongest association of the combined criteria of a quantitative change of 0.3 mg/dl in creatinine and oliguria (adjusted odds ratio of 3.7). These data strongly support the prognostic value of a small increase in serum creatinine; however, since the vast majority of patients met both the urine output and serum creatinine criteria it is unclear what is the diagnostic utility of the urine output criteria. The AKIN criteria recognized that the hydration state, use of diuretics, and presence of obstruction can influence the urine volume, hence the need to consider the clinical context. Barrentes et al.’s study (23) does not provide these details, however the association of oliguria with adverse outcomes is maintained. Future studies should include a clear method to assess urine flow rates and define the time sequence of changes in serum creatinine and urine output. This study also provides some insights to other components incorporated in the AKIN definition. The time sequence of 48 hrs was selected to ensure that the process was acute and representative of events within a clinically relevant time period. It was acknowledged that the criteria require two creatinine values to be available within any 48 hr time window. Interestingly, the majority of AKI patients met these criteria in the first 48 hrs of ICU admission (23). It is evident that the frequency of serum creatinine measurements and urine output (e.g., hourly vs. every 8 hrs) will influence the ability to diagnose AKI. Given the worse outcomes once AKI has developed; early diagnosis offers opportunities for earlier intervention. The current standard of care in most ICUs worldwide is to measure serum creatinine every 24 hrs and summate total urine output every 8 hrs. Assessment of hourly urine flow rates and every 12 hr serum creatinine value for trends will improve our diagnostic ability and enhance opportunities for prevention and therapy for AKI. As changes in volume status can influence serum creatinine levels (24) the AKIN criteria recommended that the diagnostic criteria would be utilized only after an optimal state of hydration had been achieved without delineating the amount and type of fluid used. The current study demonstrates that in over 40% of the patients with AKI, fluid challenge information was unavailable. Only three patients responded to a fluid challenge (23). These data demonstrate a need to develop and test a standard approach to fluid challenge for patients with creatinine and urine output trends meeting AKI criteria. The use of a 500 ml saline bolus appears promising but would need to be tested in a prospective study. Lack of adequate documentation of fluid balance *See also p. 1397.