What is the most accurate way to assess true kidney function and Glomerular Filtration Rate (GFR)?

The Most Accurate Method for Assessing True Kidney Function and GFR

Direct measurement of GFR using exogenous filtration markers is the most accurate method to assess true kidney function, though it is often impractical for routine clinical use. 1

Hierarchy of GFR Assessment Methods

Gold Standard: Measured GFR (mGFR)

• Uses clearance of exogenous markers that are:
  • Filtered without secretion or reabsorption by renal tubules
  • Exclusively eliminated by kidneys unbound to proteins 1
• Examples of exogenous filtration markers:
  • Inulin (historical gold standard)
  • Iohexol
  • Iothalamate 1
• Advantages:
  • Removes effect of endogenous non-GFR determinants 1
  • Most accurate assessment of true kidney function 1
• Disadvantages:
  • Labor-intensive and expensive
  • Impractical for routine clinical monitoring
  • May involve radiation exposure (with radioisotopes) 1

Next Best Option: Combined Creatinine-Cystatin C Equation

• The 2024 KDIGO guidelines recommend using eGFRcr-cys when eGFRcr is less accurate and GFR affects clinical decision-making 1
• Provides better precision and accuracy than either marker alone 2, 3
• Improves classification of patients with borderline GFR values 2
• Reduces the need for ethnicity coefficients in diverse populations 4

When to Use Cystatin C Alone

• Consider in specific populations where creatinine is affected by non-GFR determinants:
  • Eating disorders
  • Extreme athletes/bodybuilders
  • Amputations
  • Spinal cord injuries
  • Severe obesity 1

Clinical Algorithm for GFR Assessment

1. Initial Assessment: Use serum creatinine and an estimating equation (eGFRcr) 1

2. Consider potential sources of error in eGFRcr:

   • Is the patient's muscle mass significantly different from average?
   • Are there medications affecting creatinine secretion?
   • Does the patient have conditions affecting creatinine generation?

3. If eGFRcr may be inaccurate OR more accurate assessment is needed:

   • Measure cystatin C and calculate eGFRcr-cys 1

4. If even more accurate assessment is needed for critical clinical decisions:

   • Measure GFR directly using exogenous filtration markers 1

Special Clinical Situations

• Borderline GFR (45-59 ml/min/1.73 m²) without other markers of kidney damage:

  • Measure cystatin C to confirm CKD diagnosis 1
  • If eGFRcys/eGFRcr-cys ≥60 ml/min/1.73 m², CKD is not confirmed 1

• Class III obesity:

  • eGFRcr-cys has been demonstrated to be most accurate 1

• Liver transplant recipients:

  • Equations with cystatin C are most accurate 1
  • Of creatinine-based equations, CKD-EPI-creatinine and MDRD-4 are most accurate 1

Common Pitfalls to Avoid

1. Relying solely on serum creatinine values:

   • Affected by muscle mass, diet, age, and medications
   • Poor sensitivity for detecting moderate GFR reduction 5

2. Ignoring non-GFR determinants of cystatin C:

   • Affected by thyroid dysfunction, high-dose glucocorticoids, and inflammation 5

3. Overinterpreting small changes in creatinine/cystatin C:

   • Small initial increases represent significant decreases in GFR due to non-linear relationship 6

4. Failing to consider laboratory variability:

   • Different creatinine assay methods can affect results 7
   • Ensure laboratory uses standardized methods traceable to reference materials 1

By following this approach to GFR assessment, clinicians can obtain the most accurate evaluation of kidney function based on clinical circumstances, balancing precision with practicality to optimize patient outcomes related to morbidity, mortality, and quality of life.