Acute Kidney Injury - Basic Research and Clinical Practice. Группа авторов

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 m^2	≤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 m^2	<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 in 97 centers conducted on patients during the first week of ICU admission [7]. By applying the KDIGO classification, the authors analyzed data from more than 1,800 patients and found that 57% of them had some level of AKI severity (18, 9, and 30% for classes 1, 2 and 3 respectively). The study confirmed a stepwise increase in mortality with increasing AKI severity (stage 1: OR 2; stage 2: OR 4; stage 3: OR 7). Stages 2 and 3 remained associated with mortality even after adjustment for several confounders. Interestingly, surviving AKI patients of this large cohort showed, at ICU discharge, significantly worse renal function (4.5% were dialysis dependent and about half of them displayed an eGFR <60 mL/min/1.73 m²) compared to non-AKI patients.

      Serum Creatinine Criteria for AKI Diagnosis

      SCr, a metabolite of creatine (synthesized from glycine and arginine in liver, pancreas and kidneys) is excreted unchanged into urine. SCr is one of the most commonly measured analytes in clinical practice worldwide, since the cost-benefit ratio is undoubtedly favorable. Nonetheless, although SCr remains a landmark biomarker in the diagnosis and classification of AKI, the relationship between SCr and GFR should be taken into consideration in order to keep in mind some limitations for AKI diagnosis:

• SCr levels tend to remain within normal values until approximately 50% of nephrons are lost or when the GFR fall to 60 mL/min/1.73 m² [8]. For example, kidney donors maintain, after nephrectomy, normal SCr levels (and eGFR) despite having lost an entire kidney. On the contrary,