How can I calculate a patient’s estimated glomerular filtration rate (eGFR) using the CKD‑EPI equation?

How to Calculate eGFR Using the CKD-EPI Equation

Use the 2021 race-free CKD-EPI creatinine equation as your initial method for calculating eGFR in adult patients, and add cystatin C measurement when creatinine-based estimates are unreliable due to extremes of muscle mass, body size, malnutrition, or when precision is critical for clinical decision-making. 1, 2

The Standard CKD-EPI Creatinine Equation

• The 2021 CKD-EPI equation is the preferred estimating equation for routine GFR assessment in adults, as it performs better than the MDRD equation, especially at GFR levels above 60 mL/min/1.73 m² 1, 2

• Clinical laboratories should automatically report eGFR alongside serum creatinine values, rounded to the nearest whole number and expressed as mL/min/1.73 m² 1, 2

• The equation requires only serum creatinine (calibrated to international reference standards using enzymatic assays), age, and sex—race coefficients should not be used 1, 2

• For most adults without conditions affecting creatinine levels independent of GFR, this creatinine-based estimate (eGFRcr) provides a reasonable initial assessment 1, 3

When Creatinine-Based eGFR Becomes Unreliable

Critical situations requiring alternative methods:

• Extremes of muscle mass (very low or very high) alter creatinine generation independent of kidney function, making eGFRcr inaccurate 1, 3, 2

• Severe malnutrition or muscle wasting conditions compromise accuracy, as creatinine production depends heavily on muscle mass 3, 4

• Obesity class III (BMI >40 kg/m²) reduces eGFRcr reliability due to altered body composition 3

• Advanced cirrhosis or cancer with high cell turnover (high catabolism/inflammation) renders eGFRcr unreliable 1, 3

• Dietary factors, particularly high protein or meat intake, can affect creatinine levels independent of GFR 3

The Combined Creatinine-Cystatin C Equation

When eGFRcr is expected to be inaccurate and GFR affects clinical decision-making, measure cystatin C and calculate eGFRcr-cys using the combined CKD-EPI equation. 1, 3, 2

• The combined CKD-EPI creatinine-cystatin C equation consistently outperforms either marker alone, correctly classifying GFR in 62% of cases compared to 38% for creatinine alone 2

• Cystatin C is produced by all nucleated cells and is less influenced by muscle mass, diet, age, sex, and race compared to creatinine 3

• The combined equation provides more accurate GFR estimates overall and particularly in patients with large discordances between eGFRcr and eGFRcys 1

Important caveats for cystatin C:

• Exogenous glucocorticoid use increases serum cystatin C levels, potentially underestimating eGFR 1, 3

• High catabolic states and thyroid dysfunction can affect cystatin C accuracy 3, 2

• Medications affecting creatinine (trimethoprim, cimetidine, anabolic steroids) necessitate cystatin C measurement 3

When Direct GFR Measurement Is Required

For critical clinical decisions requiring precise GFR, measure GFR directly using exogenous filtration markers rather than relying on estimating equations. 1, 3, 2

• Measured GFR using iothalamate, iohexol, or other exogenous markers is the gold standard when precision is essential 1, 3, 2

• Specific indications for measured GFR:

  • Dosing chemotherapeutic agents or highly nephrotoxic drugs with narrow therapeutic windows 1, 2
  • Patients with extreme body composition abnormalities where even eGFRcr-cys may be inaccurate 1, 3
  • Critical drug dosing decisions where residual inaccuracy of estimating equations (13% differ from measured GFR by >30%) is unacceptable 1, 3

• If measured GFR is unavailable, consider 24-hour urine creatinine clearance as an alternative, though it overestimates GFR by approximately 10-20% 1, 3

Practical Clinical Algorithm

Step 1: Obtain serum creatinine (enzymatic assay, calibrated to international standards) 1, 3

Step 2: Calculate eGFRcr using the 2021 race-free CKD-EPI equation with patient's age and sex 1, 2

Step 3: Assess clinical context for conditions that compromise eGFRcr accuracy:

• Extremes of muscle mass or body size
• Malnutrition or muscle wasting
• Advanced cirrhosis or high catabolic states
• Medications affecting creatinine secretion 3, 2

Step 4: If eGFRcr is expected to be inaccurate:

• Measure serum cystatin C
• Calculate eGFRcr-cys using the combined CKD-EPI equation 1, 3, 2

Step 5: If eGFRcr-cys is still expected to be inaccurate or precision is critical:

• Arrange measured GFR using exogenous filtration markers
• If unavailable, consider 24-hour urine creatinine clearance 3, 2

Critical Pitfalls to Avoid

• Never rely on serum creatinine alone without calculating eGFR—approximately 60% of patients with abnormal renal function by eGFR have normal serum creatinine 3

• Do not ignore clinical context suggesting altered creatinine generation, as this leads to systematic errors in GFR estimation 3, 2

• For drug dosing in patients with extreme body sizes, back-calculate to absolute clearance (mL/min) rather than using normalized values (mL/min/1.73 m²) to avoid underdosing larger patients or overdosing smaller patients 1, 2

• Avoid using eGFR in non-steady-state conditions such as acute kidney injury, as all estimating equations are only valid in steady-state 1

• Do not assume eGFRcr accuracy when assessing GFR changes over time without considering potential sources of error, particularly in hospitalized or malnourished patients 3, 4