How is Glomerular Filtration Rate (GFR) calculated?

Calculation of Glomerular Filtration Rate (GFR)

GFR is best estimated using validated prediction equations that incorporate serum creatinine and other variables such as age, sex, race, and body size, rather than relying on serum creatinine measurements alone. 1

Primary Estimation Methods

Creatinine-Based Equations

• The Modification of Diet in Renal Disease (MDRD) Study equation is widely used and provides useful estimates of GFR in adults 1:

  • Abbreviated MDRD equation: GFR = 186 × (serum creatinine)^-1.154 × (age)^-0.203 × (0.742 if female) × (1.212 if African American) 1

• The Cockcroft-Gault equation is another commonly used formula 1:

  • GFR = [(140 - age) × weight (kg) × 0.85 if female] / [72 × serum creatinine (mg/dL)] 1

• The 2021 CKD-EPI creatinine equation (race-free) is now recommended as it performs better than the MDRD equation, especially at higher GFR levels 1, 2:

  • This equation has improved precision and less bias, particularly for GFR values >60 mL/min/1.73 m² 2

Cystatin C-Based and Combined Equations

• The 2012 CKD-EPI cystatin C equation provides an alternative when creatinine-based estimates may be less reliable 1

• The combined creatinine-cystatin C equation (CKD-EPI eGFRcr-cys) offers improved accuracy, particularly in patients with discordance between creatinine and cystatin C-based estimates 1

Factors Affecting GFR Estimation

• Serum creatinine alone is inadequate for GFR estimation because 1:

  • It's affected by factors other than GFR (muscle mass, diet, age)
  • GFR must decline to approximately half the normal level before serum creatinine rises above normal limits
  • In elderly patients, age-related decline in muscle mass reduces creatinine generation, masking reduced GFR

• Laboratory standardization is crucial 1:

  • Clinical laboratories should calibrate serum creatinine assays using international standards
  • Different methods of creatinine measurement (Jaffe vs. enzymatic PAP) can affect results 1

Special Considerations

• For patients with extremes of age or body size, severe malnutrition or obesity, diseases of skeletal muscle, paraplegia, vegetarian diet, rapidly changing kidney function, or when calculating doses of potentially toxic drugs, direct measurement of GFR using clearance methods may be necessary 1

• In children, specialized equations such as the Schwartz formula should be used 1

• In elderly patients (≥70 years), equations specifically validated in older populations may be more accurate 3

Direct GFR Measurement Methods

• Gold standard: Inulin clearance (laborious and expensive) 1

• Alternative exogenous markers 1:

  • Iothalamate clearance
  • Iohexol clearance

• Timed urine collections for creatinine clearance 1:

  • As GFR falls, creatinine clearance progressively overestimates true GFR
  • At lower GFR levels (15-20 mL/min), an average of creatinine and urea clearances provides a more valid approximation

Clinical Implementation

• Clinical laboratories should report estimated GFR using a prediction equation in addition to reporting serum creatinine measurement 1

• Use of the same equation within geographical regions is recommended for consistency 1

• Race-based adjustments in GFR equations should be avoided 1

• For critical clinical decisions (e.g., dosing of nephrotoxic medications), more precise GFR measurement may be warranted 1, 4

Common Pitfalls

• Overreliance on serum creatinine alone can lead to missed diagnosis of reduced kidney function, especially in elderly patients or those with reduced muscle mass 1

• Different equations may yield significantly different GFR estimates, particularly in healthy and younger individuals 5

• Creatinine-based and cystatin C-based estimates may show different associations with cardiovascular risk factors 5

• Failure to consider non-GFR determinants of filtration markers can lead to inaccurate GFR assessment 1, 4