How do you test estimated Glomerular Filtration Rate (eGFR)?

Testing Estimated Glomerular Filtration Rate (eGFR)

For initial assessment of kidney function, use serum creatinine with a validated GFR estimating equation rather than relying on serum creatinine alone. 1

Initial eGFR Testing Approach

Primary Method

• Use serum creatinine with a validated GFR estimating equation (eGFRcr)
  • The recommended equation is the race-free 2021 CKD-EPI GFR equation 1
  • Clinical laboratories should measure serum creatinine using assays with calibration traceable to international standard reference materials 1
  • Report eGFR in mL/min per 1.73 m² rounded to the nearest whole number 1

When to Use Additional Testing

Consider additional testing in the following situations:

• When eGFRcr is less accurate due to:
  • Altered muscle mass (very high or low)
  • Altered creatinine metabolism
  • Medications affecting tubular secretion of creatinine
  • Extremes of body size or age
  • Pregnancy
  • Severe liver disease
  • Diet high in cooked meat (temporarily elevates creatinine)

Confirmatory Testing Options

Combined Creatinine-Cystatin C Testing

• When to use: For patients with eGFRcr 45-59 mL/min/1.73 m² without other markers of kidney damage who need confirmation of CKD 1
• Method: Use the combined creatinine-cystatin C equation (eGFRcr-cys)
• Advantage: More accurate than either marker alone, especially for persons with discordance between eGFRcr and eGFRcys 1

Measured GFR

• When to use: For critical clinical decisions where precise GFR is needed (e.g., kidney-cleared chemotherapeutic agents, potential kidney donors) 1
• Method: Measure GFR using plasma or urinary clearance of exogenous filtration markers
• Examples: Iothalamate, iohexol, or DTPA clearance

Timed Urine Collection

• When to use: If measured GFR is not available and eGFRcr-cys is thought to be inaccurate 1
• Method: 24-hour urine collection for measured creatinine clearance
• Limitation: Often inaccurate due to collection errors

Interpretation of eGFR Results

GFR Categories

• G1: ≥90 mL/min/1.73 m² (Normal or high)
• G2: 60-89 mL/min/1.73 m² (Mildly decreased)
• G3a: 45-59 mL/min/1.73 m² (Mildly to moderately decreased)
• G3b: 30-44 mL/min/1.73 m² (Moderately to severely decreased)
• G4: 15-29 mL/min/1.73 m² (Severely decreased)
• G5: <15 mL/min/1.73 m² (Kidney failure)

Confirming CKD Diagnosis

• CKD is confirmed when eGFR <60 mL/min/1.73 m² persists for >3 months 1
• For eGFR values near the threshold, repeat testing is recommended
• If eGFRcr is 45-59 mL/min/1.73 m² without other markers of kidney damage, measure cystatin C and calculate eGFRcr-cys for confirmation 1

Important Considerations

Laboratory Standards

• Laboratories should:
  • Use standardized creatinine assays with minimal bias compared to isotope-dilution mass spectrometry reference methodology 1
  • Report eGFR along with serum creatinine 1
  • Specify the equation used when reporting eGFR 1
  • Consider enzymatic creatinine assays for children (more accurate than Jaffe method) 1

Avoiding Common Pitfalls

• Race-based calculations: Avoid using race in eGFR calculations 1
• Single measurements: Don't rely on a single eGFR value for clinical decisions; confirm with repeat testing
• Ignoring clinical context: Consider factors that might affect creatinine independent of GFR
• Over-interpreting small changes: Understand the inherent variability in eGFR measurements
• Using inappropriate equations: Use equations validated for the specific population (e.g., different equations for children) 1

Special Populations

• Children: Use pediatric-specific equations validated in comparable populations 1
• Elderly: Consider age-related decline in GFR when interpreting results
• Pregnant women: Normal GFR increases by 40-50% during pregnancy 2

By following these evidence-based recommendations for eGFR testing, clinicians can more accurately assess kidney function, leading to improved detection and management of kidney disease, which ultimately impacts morbidity and mortality outcomes.