unit (ICU) and it is associated with severe short- and long-term complications, including increased mortality [1]. AKI is characterized by a rapid decline in kidney function mostly referred to a decrease in glomerular filtration rate (GFR). Since the (re)-establishment and optimization of hemodynamics with adequate intravascular volume, cardiac output and perfusion pressure are the only effective therapeutic interventions in patients with decreased GFR [2], early identification and diagnosis is crucial. This chapter reviews the evolution of diagnostic criteria of AKI, both in adult and pediatric setting, the currently recommended definition, and its major limitations.
AKI Definition and Classification in Adult Patients
The field of critical care nephrology and AKI has been hampered by the long-standing lack of a standardized system to diagnose and classify this syndrome. Over the years, a number of different definitions have been applied without well-defined terms identifying “acute renal failure” or “acute tubular necrosis.” As a demonstration of the confusion that reigned around renal failure in the past, a survey conducted in 2004 during an international meeting on Critical Care Nephrology showed that more than 200 different definitions of AKI were provided by the involved clinicians [3]. The first innovative and revolutionary step in the AKI definition was performed by the Dialysis Quality Initiative (ADQI) Group in 2004 [4]. The ADQI consensus founded the Risk, Injury, Failure, Loss and End-stage Kidney (RIFLE) criteria identifying the following categories: “at Risk” is the least severe category of AKI, followed by “Injury,” “Failure,” “Loss” and “End-stage renal disease” (Table 1). Diagnosis and staging severity were based on two “strategic” parameters: a rise in serum creatinine level (SCr) from a baseline value and/or a decrease in urine output (UO) per kilogram of body weight over a specified time period (7 days) as surrogates for GFR. This first classification did not aim to predict mortality or adverse outcomes; it also did not aim to trigger standardized therapeutic interventions but was conceived to start a fundamental process for AKI definition and “exact” detection, at least for epidemiologic purposes. Furthermore, a primary message was clearly stated: AKI is not a “yes” or “no” condition but is characterized by a progressive disease severity, where the more advanced the renal dysfunction is the worse the clinical picture and therefore the outcomes would be. In 2007, the AKI definition evolved from the RIFLE criteria into the AKI Network classification, known as the Acute Kidney Injury Network (AKIN) criteria [5] (Table 1). According to the AKIN criteria, AKI severity has been divided into 3 stages of escalating severity (1, 2, and 3), while the old RIFLE-Loss and end-stage renal disease were eliminated, since considered prognostic classes, without classification purposes. Another relevant difference between the RIFLE and AKIN criteria is the 48-h time-frame within which the diagnosis of AKI must be made to fulfill the AKIN criteria. The last classification released in 2012 was born in an attempt of reconciling all previous ones: The Kidney Disease Improving Global Outcomes (KDIGO) consensus classification [6] (Table 1). According to the KDIGO criteria, AKI is diagnosed if SCr increases by 0.3 mg/dL (or ≥26.5 μmol/L) in ≤48 h, or rises to ≥1.5-fold from baseline within the prior 7 days and/or a decrease in UO <0.5 mL/kg/h for 6–12 h. This initial dysfunction identifies the stage 1 of AKI. AKI stage 2 is reached when there is an increase in SCr 2.0–2.9 times from baseline and/or UO <0.5 mL/kg/h for ≥12 h. Finally, stage 3 occurs when there is an increase in SCr 3.0 times from baseline or to 4 mg/dL (or ≥353.6 μmol/L), or initiation of renal replacement therapy irrespective of SCr and/or UO <0.3 mL/kg/h for ≥24 h, or anuria for ≥12 h. In patients <18 years, there is a decrease in estimated GFR (eGFR) to <35 mL/min/1.73 m2.
Table 1. RIFLE, pRIFLE, AKIN, KDIGO, neonatal KDIGO criteria for acute kidney injury
| System | SCr criteria | UO criteria |
| RIFLE criteria | ||
| Risk | SCr increase to 1.5-fold or GFR decrease >25% from baseline | <0.5 mL/kg/h for 6 h |
| Injury | SCr increase to 2.0-fold or GFR decrease >50% from baseline | <0.5 mL/kg/h for 12 h |
| Failure | SCr increase to 3.0-fold or GFR decrease >75% from baseline or SCr ≥4 mg/dL (≥354 μmol/L) with an acute increase of at least 0.5 mg/Dl (44 μmol/L) | ≤0.3 mL/kg/h × 24 h or anuria × 12 h |
| Loss | Persistent AKI = complete loss of kidney function >4 weeks | |
| End-stage renal disease | End stage kidney disease (>3 months) | |
| pRIFLE criteria | ||
| Risk | eCCl decrease by 25% | <0.5 mL/kg/h for 8 h |
| Injury | eCCl decrease by 50% | <0.5 mL/kg/h for 16 h |
| Failure | eCCl decrease by 75% or eCCl <35 mL/min/1.73 m2 | ≤0.3 mL/kg/h × 24 h or anuria × 12 h |
| Loss | Persistent complete loss of kidney function >4 weeks | |
| End-stage renal disease | End stage kidney disease (>3 months) | |
| AKIN criteria | ||
| Stage 1 | SCr increase ≥0.3 mg/dL (≥26.5 μmol/L) or increase to 1.5- to 2.0-fold from Baseline | <0.5 ml/kg/h for 6 h |
| Stage 2 | SCr increase >2.0- to 3.0-fold from baseline | <0.5 mL/kg/h for 12 h |
| Stage 3 | SCr increase >3.0-fold from baseline or serum creatinine ≥4.0 mg/dL (≥354 μmol/L) with an acute increase of at least 0.5 mg/dL (44 μmol/L) or need for RRT | <0.3 mL/kg/h for 24 h or anuria for 12 h or needfor RRT |
| KDIGO criteria | ||
| Stage 1 | SCr increase ≥0.3 mg/dL (≥26.5 μmol/L)* or increase to 1.5- to 2.0-fold from baseline§ | <0.5 mL/kg/h for 6–12 h |
| Stage 2 | SCr increase >2.0- to 2.9-fold from baseline | <0.5 mL/kg/h for ≥12 h |
| Stage 3 | SCr increase >3.0-fold from baseline or serum creatinine ≥4.0 mg/dL (≥354 μmol/L) with an acute increase of at least 0.5 mg/dL (44 μmol/L) or initiation of RRT or, in patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m2 | <0.3 mL/kg/h for 24 hAnuria for ≥12 h |
| Neonatal KDIGO criteria (2015–2016) | ||
| Stage 1 | SCr ≥0.3 rise within 48 horSCr ≥1.5- to 1.9-fold rise from baseline (previous lowest value) within 7 days | <1 mL/kg/h for 24 h |
| Stage 2 | SCr increase >2.0- to 2.9-fold from baseline | <0.5 mL/kg/h for ≥24 h |
| Stage 3 | SCr increase >3.0-fold from baseline or serum creatinine ≥2.5 mg/dL (221 μmol/L) or initiation of RRT | <0.3 mL/kg/h for 24 h |
| SCr, serum creatinine; UO, urine output; eCCl, estimated creatinine clearance (according to Schwartz formula, as per pRIFLE); GFR, glomerular filtration rate; AKI, acute kidney injury; RRT, renal replacement therapy; eGFR, estimated glomerular filtration rate. * Within 48 h; § within the prior 7 days. | ||
Although the KDIGO definition of AKI evidently represents a fundamental step to easily, rapidly, and cost-effectively identify these patients, AKI is diagnosed based on SCr rise and/or fall in UO, two markers that are not renal-specific and have important limitations addressed in the following paragraphs.
The most recent epidemiologic research on AKI diagnosis is the Acute Kidney Injury-Epidemiologic Prospective Investigation study, an international cross-sectional study performed
