Recent Classification Systems for Acute Kidney Injury in Critically Ill Patients
Current Standard: KDIGO Criteria
The KDIGO criteria are the current gold standard for AKI diagnosis and staging in critically ill patients, having harmonized and superseded both RIFLE and AKIN classifications. 1 The 2020 KDIGO nomenclature guidelines explicitly state that previous classifications including RIFLE and AKIN should be avoided. 1
KDIGO Definition of AKI
AKI is diagnosed when any one of the following criteria is met: 1, 2
- Serum creatinine increase ≥0.3 mg/dL within 48 hours, OR
- Serum creatinine increase to ≥1.5 times baseline within 7 days, OR
- Urine output <0.5 mL/kg/h for 6 consecutive hours
KDIGO Staging System
- SCr 1.5-1.9 times baseline OR increase ≥0.3 mg/dL
- Urine output <0.5 mL/kg/h for 6-12 hours
- SCr 2.0-2.9 times baseline
- Urine output <0.5 mL/kg/h for ≥12 hours
- SCr ≥3.0 times baseline OR increase to ≥4.0 mg/dL (with acute rise of ≥0.3 mg/dL) OR initiation of renal replacement therapy
- Urine output <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours
- In patients <18 years: eGFR decrease to <35 mL/min/1.73 m²
The staging is determined retrospectively by the most severe criterion met, and progression through stages correlates strongly with increased mortality. 3, 2
Historical Classification Systems
RIFLE Criteria (Superseded)
The RIFLE system was the first consensus definition proposed by the Acute Dialysis Quality Initiative: 1, 3
- Risk: SCr increase to 1.5× baseline; UO <0.5 mL/kg/h for 6h
- Injury: SCr increase to 2× baseline; UO <0.5 mL/kg/h for 12h
- Failure: SCr increase to 3× baseline OR SCr ≥4 mg/dL with acute increase of 0.5 mg/dL; UO <0.3 mL/kg/h for 24h or anuria for 12h
- Loss: Need for RRT for >4 weeks
- End-stage: Need for RRT for >3 months
The RIFLE criteria required changes to be abrupt (within 1-7 days) and sustained (≥24 hours). 1
AKIN Criteria (Superseded)
The AKIN classification (2007) modified RIFLE by: 1, 3
- Adding the 0.3 mg/dL increase within 48 hours to define Stage 1 AKI
- Shortening the timeframe from 7 days to 48 hours for creatinine changes
- Removing GFR criteria as markers of AKI
- Eliminating the outcome categories (Loss and End-stage)
- Stipulating that adequate fluid resuscitation and exclusion of urinary obstruction should precede diagnosis 1
AKIN used three stages (1,2,3) corresponding roughly to RIFLE's Risk, Injury, and Failure categories. 1
Key Differences Between AKIN and KDIGO
KDIGO merged and refined both RIFLE and AKIN systems: 1, 3
Timeframe for creatinine changes:
Stage 3 criteria modification:
Pediatric considerations:
- KDIGO added specific criteria for patients <18 years: eGFR decrease to <35 mL/min/1.73 m² defines Stage 3 1
Classification approach:
- KDIGO recommends classifying by both cause and stage (e.g., "AKI stage 3 due to ATN") rather than stage alone 1
Validation and adoption:
Clinical Significance and Validation
Even the 0.3 mg/dL creatinine increase is independently associated with approximately 4-fold increase in hospital mortality, validating the inclusion of this sensitive criterion. 3, 2 Large epidemiologic studies confirm that AKI occurs in approximately 50% of critically ill ICU patients using KDIGO criteria, with stepwise mortality increases across stages. 6, 4
Important caveat: The KDOQI US Commentary raised concerns about potential overdiagnosis and unnecessary consultations when applying KDIGO criteria rigidly to guide clinical management, particularly the Stage 3 criterion in CKD patients. 1, 3
Early and Novel Biomarkers of AKI
Established Early Biomarkers
Neutrophil Gelatinase-Associated Lipocalin (NGAL): 1
- Detects tubular injury before creatinine rises
- Can identify kidney damage in the absence of functional decline
Kidney Injury Molecule-1 (KIM-1): 1
- Marker of proximal tubular injury
- Useful for early AKI detection
Newest Biomarkers
Cell Cycle Arrest Biomarkers: 7
- Tissue Inhibitor of Metalloproteinase-2 (TIMP-2)
- Insulin-like Growth Factor-Binding Protein 7 (IGFBP7)
- These markers indicate cellular stress and early tubular damage 7
Cystatin C: 5
- Less affected by muscle mass, age, and sex compared to creatinine
- Cystatin C-based criteria show higher predictive ability (AUC 0.70) for 28-day mortality compared to KDIGO, AKIN, or RIFLE 5
- Concordance with KDIGO is 95.9%, higher than with RIFLE or AKIN 5
Proposed Integrated Approach
KDIGO Stage 1 substaging based on biomarkers: 7
- Stage 1S: Early kidney injury detected by biomarkers but not yet meeting creatinine/UO criteria
- Stage 1A: Meets creatinine/UO criteria without biomarker elevation
- Stage 1B: Meets both functional criteria and has elevated damage biomarkers
This approach combines damage biomarkers with functional criteria to improve diagnostic accuracy and risk stratification. 7
Special Considerations for Critically Ill Patients
Limitations of Urine Output Criteria
In cirrhotic patients with ascites: 7, 2
- Focus exclusively on serum creatinine changes
- Urine output criteria are unreliable due to avid sodium retention despite relatively normal GFR
- Diuretic therapy further confounds interpretation
- A creatinine threshold of ≥1.5 mg/dL predicts AKI progression and worse prognosis in this population 7
Limitations of Creatinine Criteria
Serum creatinine significantly overestimates kidney function in: 7
- Patients with muscle wasting
- Volume expansion states
- Hyperbilirubinemia (interferes with colorimetric assays)
- Increased tubular secretion of creatinine
Acute Kidney Disease (AKD) Concept
AKD bridges the gap between AKI and CKD: 1, 2
- Defined as kidney dysfunction lasting 7-90 days after AKI onset
- Includes patients with GFR <60 mL/min/1.73 m² for ≤3 months, or GFR decrease ≥35%, or SCr increase >50% for ≤3 months 1
- AKD persisting >90 days transitions to CKD 2
- Patients should be evaluated 3 months after AKI for resolution or progression to CKD 1