How is glomerular filtration rate (GFR) assessed in patients with acute kidney injury (AKI)?

Assessment of GFR in Acute Kidney Injury

In patients with AKI, GFR should NOT be estimated using standard equations (MDRD, CKD-EPI, Cockcroft-Gault) because these require steady-state creatinine conditions that do not exist in AKI; instead, use serial serum creatinine measurements and urine output monitoring for AKI staging, with timed urine creatinine clearance as an alternative when GFR estimation is necessary. 1

Why Standard eGFR Equations Fail in AKI

Standard GFR estimation equations are fundamentally unsuitable for AKI patients because:

• MDRD and CKD-EPI equations were validated only in patients with stable CKD, not in acute settings 1
• These equations require serum creatinine to be in steady-state, which never occurs during the dynamic creatinine changes characteristic of AKI 1
• Standard equations can overestimate GFR by as much as 80% (Cockcroft-Gault) or 33% (MDRD) in AKI patients 2
• The equations cannot account for rapid changes in creatinine generation, fluid balance shifts, or muscle mass loss that occur in critically ill patients 1, 2

Recommended Approach: KDIGO AKI Staging

The primary method for assessing kidney function in AKI is KDIGO staging based on:

Serum Creatinine Criteria

• Stage 1: 1.5-1.9 times baseline OR ≥0.3 mg/dL increase within 48 hours 1
• Stage 2: 2.0-2.9 times baseline 1
• Stage 3: 3.0 times baseline OR increase to ≥4.0 mg/dL OR initiation of RRT 1

Urine Output Criteria

• Stage 1: <0.5 mL/kg/h for 6-12 hours 1
• Stage 2: <0.5 mL/kg/h for 12 hours 1
• Stage 3: <0.3 mL/kg/h for 24 hours OR anuria for 12 hours 1

Monitor serum creatinine and urine output serially rather than attempting to calculate a single GFR value 1

Alternative Methods When GFR Estimation Is Required

Timed Urine Creatinine Clearance

• Short timed urine collections (4-24 hours) can estimate GFR but have significant limitations 1
• Creatinine clearance typically overestimates true GFR in AKI because creatinine undergoes tubular secretion 1
• Establishing steady-state conditions for accurate measurement is often impossible in ICU patients 1
• For patients on RRT, 24-hour urine collections can assess residual kidney function using creatinine and urea clearance 1

Kinetic GFR Approaches (Investigational)

The ADQI consensus identifies promising but not yet validated approaches:

• Kinetic eGFR (KeGFR): Estimates GFR based on creatinine kinetics rather than steady-state assumptions 1

  • Shows good correlation with measured GFR (r=0.68) but wide limits of agreement (>40 mL/min/1.73 m²) 3
  • Requires further validation before clinical use 1

• Jelliffe equation: Calculates GFR using volume of distribution and creatinine kinetics 1

  • When adjusted for fluid balance (Modified Jelliffe), underestimates GFR by only 2% compared to 10% without adjustment 2
  • Shows good correlation (r=0.73) but still has wide limits of agreement 3
  • Needs validation in diverse patient populations 1

Gold Standard Methods (Impractical for Routine Use)

• Iohexol clearance, inulin clearance, or ⁵¹Cr-EDTA provide accurate GFR measurement but are time-consuming, laborious, and unsuitable for ICU patients 1
• Consider these methods only in select cases, such as assessing recovery in patients who lost muscle mass during critical illness 1

Special Considerations for RRT-Dependent Patients

Current tools are insufficient to accurately assess kidney function in patients receiving acute RRT 1

• Standard serum creatinine is unreliable due to muscle mass loss during critical illness 1
• Consider cystatin C or direct GFR measurement (iohexol clearance) in selected cases to assess recovery independent of muscle mass 1
• Monitor pre-dialysis serum creatinine values weekly and assess residual kidney function with 24-hour urine collections 1

Critical Pitfalls to Avoid

• Never use MDRD or CKD-EPI equations to guide clinical decisions in AKI patients 1
• Do not rely on a single creatinine value; AKI diagnosis requires demonstrating change from baseline 1
• When baseline creatinine is unknown, back-calculating from an assumed eGFR of 75 mL/min/1.73 m² is sensitive for detecting AKI but may overestimate incidence in populations with high CKD prevalence 1
• Recognize that even "improved" kinetic equations have limits of agreement >40 mL/min/1.73 m², making them unreliable for precise clinical decisions 3
• Adjust medication dosing based on AKI stage and clinical trajectory rather than calculated eGFR values 1, 4

Practical Clinical Algorithm

1. Establish baseline creatinine (or estimate if unavailable) 1
2. Monitor serial creatinine and urine output to stage AKI severity 1
3. Use KDIGO staging (not eGFR) to guide management decisions 1
4. If precise GFR needed (e.g., for specific drug dosing), consider short timed urine creatinine clearance with awareness of its limitations 1
5. Reassess daily for persistent AKI (>7 days), which may warrant additional diagnostic workup including kidney biopsy 1, 5
6. Transition to GFR-based staging only after creatinine stabilizes (typically after 3 months, defining transition to CKD) 1, 4