What are the stages of Acute Kidney Injury (AKI)?

Stages of Acute Kidney Injury (AKI)

Acute Kidney Injury is classified into three main stages based on serum creatinine (sCr) elevation and/or urine output reduction, according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Diagnostic Criteria for AKI

• AKI is defined by any of the following criteria 1, 2, 3:
  • Increase in serum creatinine ≥0.3 mg/dL (26.5 μmol/L) within 48 hours
  • Increase in serum creatinine to ≥1.5 times baseline within the previous 7 days
  • Urine volume <0.5 mL/kg/h for 6 consecutive hours

AKI Staging System

Stage 1 AKI

• Increase in serum creatinine 1.5-1.9 times baseline OR
• Increase in serum creatinine by ≥0.3 mg/dL (26.5 μmol/L) OR
• Urine output <0.5 mL/kg/h for 6-12 hours 4, 2

Stage 2 AKI

• Increase in serum creatinine 2.0-2.9 times baseline OR
• Urine output <0.5 mL/kg/h for ≥12 hours 4, 2

Stage 3 AKI

• Increase in serum creatinine ≥3.0 times baseline OR
• Increase in serum creatinine to ≥4.0 mg/dL (353.6 μmol/L) OR
• Initiation of renal replacement therapy OR
• Urine output <0.3 mL/kg/h for ≥24 hours OR
• Anuria for ≥12 hours 4, 2

Clinical Significance of AKI Staging

• The progression of AKI through stages (from stage 1 to 2 or stage 2 to 3) strongly correlates with increased mortality 4
• Even small increases in serum creatinine (≥0.3 mg/dL) are independently associated with approximately fourfold increase in hospital mortality 1, 3
• All AKI stages are independently associated with six-month mortality, with hazard ratios increasing with each stage: stage 1 (HR 2.04), stage 2 (HR 2.73), and stage 3 (HR 4.5) 5

Proposed Modifications to AKI Staging

• Some researchers have suggested subdividing Stage 1 AKI into two substages 6:
  • Stage 1a: Absolute increase in serum creatinine of 0.3 mg/dL within 48 hours
  • Stage 1b: 50% relative increase in serum creatinine within 7 days
• This modification shows clinically meaningful differences in outcomes, with stage 1b associated with higher mortality (odds ratio 10.9) compared to stage 1a (odds ratio 4.3) 6

Special Considerations in AKI Staging

• Urine output criteria may be problematic in certain patient populations, such as those with cirrhosis and ascites, who may be oliguric despite relatively normal GFR or may have increased urine output due to diuretic treatment 4, 3
• In patients with cirrhosis, serum creatinine may underestimate kidney dysfunction due to decreased creatinine formation from muscle wasting 3
• The KDIGO guideline modified criteria for stage 3 AKI to include rises in creatinine to ≥4.0 mg/dL when the rise is >0.3 mg/dL or >50% within the specified time frames 4, 1

Evolution of AKI Classification Systems

• The RIFLE classification (Risk, Injury, Failure, Loss, End-stage kidney disease) was the first standardized definition 1, 7
• The Acute Kidney Injury Network (AKIN) criteria added the ≥0.3 mg/dL rise in creatinine within 48 hours to the definition of stage 1 AKI 1, 7
• The KDIGO criteria merged elements from both RIFLE and AKIN, maintaining the 0.3 mg/dL increase within 48 hours or ≥50% increase within 7 days 4, 1, 7

Biomarkers in AKI Staging

• Newer approaches propose combining damage and functional biomarkers with clinical information to improve diagnostic accuracy 4
• A proposed modification of KDIGO stage 1 AKI includes three substages (1S, 1A, and 1B) based on biomarker presence 4
• Stage 1S identifies early kidney injury detected by biomarkers but not by creatinine and urine output criteria 4

Remember that AKI staging is determined by the highest possible stage where either the creatinine or urine output criterion is met, and staging is carried out retrospectively when the episode is complete 4, 2.