Acute Kidney Injury Definition
Acute Kidney Injury (AKI) is defined by the KDIGO criteria as an abrupt decrease in kidney function occurring over 7 days or less, diagnosed when any one of three criteria is met: serum creatinine rise ≥0.3 mg/dL within 48 hours, OR serum creatinine increase ≥50% from baseline within 7 days, OR urine output <0.5 mL/kg/h for 6 consecutive hours. 1, 2, 3
Core Diagnostic Criteria
The diagnosis requires meeting any single criterion from the following 2, 3:
- Serum creatinine increase ≥0.3 mg/dL (26 μmol/L) within 48 hours 1, 2, 3
- Serum creatinine increase to ≥1.5 times baseline (≥50% rise) within 7 days 1, 2, 3
- Urine output <0.5 mL/kg/h for ≥6 consecutive hours 1, 2, 3
The seemingly small threshold of 0.3 mg/dL was deliberately chosen because even this minimal creatinine elevation independently predicts a fourfold increase in hospital mortality, making early detection critical 1, 2, 3.
AKI Staging System
AKI severity is classified into three stages based on the most severe criterion met (either creatinine or urine output), with direct correlation between higher stages and increased mortality 2, 3:
Stage 1
- Creatinine: 1.5-1.9 times baseline OR increase ≥0.3 mg/dL 2, 3
- Urine output: <0.5 mL/kg/h for 6-12 hours 2, 3
Stage 2
Stage 3
- Creatinine: ≥3.0 times baseline OR increase to ≥4.0 mg/dL (with acute rise >0.3 mg/dL or >50%) OR initiation of renal replacement therapy 2, 3
- Urine output: <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours 2, 3
Any patient receiving renal replacement therapy is automatically classified as Stage 3 AKI regardless of creatinine or urine output values 3.
Temporal Context: AKI Within the Disease Continuum
AKI exists within a broader spectrum of kidney disease defined by duration 1, 2:
- AKI: Acute phase lasting ≤7 days 1, 2
- Acute Kidney Disease (AKD): Kidney damage/dysfunction persisting 7-90 days after the initiating event 1, 2
- Chronic Kidney Disease (CKD): Kidney disease persisting >90 days 1, 2
AKD can occur with or without preceding AKI, and patients with AKD without AKI have an adjusted hazard ratio of 2.26 for the composite outcome of incident CKD, kidney failure, or death 1. This framework captures patients whose creatinine rises slowly over 2 weeks (not meeting the 48-hour or 7-day AKI criteria) but still require intervention 1.
Critical Pitfalls in Diagnosis
Baseline Creatinine Determination
Using known creatinine values is superior to imputation methods when establishing baseline 1, 2. If a known baseline is unavailable, use the lowest creatinine value during hospitalization 2. Back-calculation from an estimated GFR of 75 mL/min/1.73 m² may overestimate AKI incidence in populations with high CKD prevalence 1.
Serum Creatinine Limitations
Serum creatinine has inherent limitations that can lead to misclassification 1, 2:
- Decreased creatinine formation in patients with muscle wasting 1
- Volume expansion diluting serum creatinine 1
- Interference with creatinine assays by elevated bilirubin 1
- Increased tubular secretion of creatinine in chronic kidney disease 2
Urine Output Criteria Considerations
Relying solely on serum creatinine without considering urine output criteria may miss cases of AKI 1. However, urine output criteria are unreliable in specific populations 1, 2:
- Cirrhotic patients with ascites who are frequently oliguric with avid sodium retention yet may maintain relatively normal GFR 1
- Patients on diuretic therapy 2
Clinical Significance
AKI is not merely a laboratory finding but a clinical syndrome associated with substantial morbidity and mortality 4. Severe AKI occurs in 5% of critically ill patients and is associated with mortality rates of 40%-70% 5. Beyond immediate mortality risk, AKI increases long-term risks of cardiovascular events, progression to CKD, and long-term mortality 4, 6.
Detection must occur in real-time based on initial marker changes rather than waiting for retrospective confirmation, making systematic laboratory monitoring essential in at-risk patients 2, 3.