How is Glomerular Filtration Rate (GFR) evaluated?

Evaluation of Glomerular Filtration Rate (GFR)

The initial assessment of GFR should use serum creatinine with an estimating equation (eGFRcr), followed by more precise measurements when clinical decisions are critical, as recommended by KDIGO guidelines. 1

Initial Assessment of GFR

• Use serum creatinine and a validated GFR estimating equation (eGFRcr) for initial assessment 1, 2
• The CKD-EPI equation is preferred for estimating GFR in most clinical settings 2
• Normal serum creatinine ranges:
  • Men: 0.7-1.3 mg/dL (62-115 μmol/L)
  • Women: 0.6-1.1 mg/dL (53-97 μmol/L) 2

Algorithmic Approach to GFR Evaluation

1. Initial Test: Measure serum creatinine and calculate eGFRcr
2. Assess Accuracy: Consider potential sources of error in eGFRcr
   • If eGFRcr is likely accurate → Use eGFRcr
   • If eGFRcr is likely inaccurate → Proceed to confirmatory testing
3. Confirmatory Testing: Measure cystatin C and calculate eGFRcr-cys
   • If eGFRcr-cys is likely accurate → Use eGFRcr-cys
   • If eGFRcr-cys is likely inaccurate or highest accuracy needed → Measure GFR directly 1, 2

When to Use Confirmatory Testing

KDIGO recommends using eGFRcr-cys when:

• eGFRcr is less accurate and GFR affects clinical decision-making 1
• Critical clinical decisions depend on accurate GFR assessment 2

Common situations requiring confirmatory testing:

• Extremes of muscle mass (very high or low)
• Malnutrition or catabolic states
• Liver disease
• Drug dosing decisions for nephrotoxic medications
• Evaluation for kidney donation 1, 2

Methods for Direct GFR Measurement

When highest accuracy is needed:

• Measure GFR using plasma or urinary clearance of exogenous filtration markers 1
• Gold standard: Inulin clearance (rarely used clinically) 3
• Practical alternatives:
  • Isotope-labeled compounds (125I-iothalamate, 51Cr-EDTA, 99mTc-DTPA)
  • Non-radioactive contrast agents (iothalamate, iohexol) 3
  • Timed urine collections for creatinine clearance (if other methods unavailable) 1, 2

Factors Affecting GFR Assessment

Non-GFR Determinants of Creatinine

• Diet: Low-protein, vegetarian, keto diets (decrease creatinine)
• Supplements: Creatine, high-protein diets (increase creatinine)
• Medications: Drugs affecting tubular secretion (trimethoprim, cimetidine)
• Muscle mass: Affects creatinine generation 2

Non-GFR Determinants of Cystatin C

• Inflammation
• Corticosteroid use
• Thyroid disorders
• Obesity 2

Common Pitfalls to Avoid

• Assuming a single abnormal result indicates chronic kidney disease

  • Confirm chronicity (≥3 months) before diagnosing CKD 1, 2
  • Consider acute kidney injury as a possible cause

• Relying solely on serum creatinine without using estimating equations

  • Always use validated equations rather than serum creatinine alone 1

• Not considering limitations of each measurement method

  • eGFRcr is less accurate in patients with abnormal muscle mass
  • eGFRcys is affected by inflammation and steroid use
  • Timed urine collections are subject to collection errors 2

• Not recognizing that GFR estimates have inherent imprecision

  • All estimates have error compared to true GFR 4
  • Consider the clinical context when interpreting results

Special Considerations

• Pediatric patients: Use specific pediatric equations; enzymatic creatinine assays preferred 1
• Elderly patients: Consider age-related decline in GFR when interpreting results
• Pregnancy: Normal GFR increases during pregnancy; standard equations may not apply
• Acute illness: GFR estimates may be less reliable during acute changes in kidney function 2

By following this algorithmic approach to GFR evaluation, clinicians can obtain accurate assessments of kidney function to guide diagnosis, staging, and management of kidney disease, as well as appropriate drug dosing decisions.