What laboratory test should be ordered to calculate estimated glomerular filtration rate (eGFR)?

Laboratory Test for Calculating eGFR

Order a serum creatinine test, which clinical laboratories will automatically use to calculate and report eGFR using the 2021 CKD-EPI creatinine equation. 1

Primary Testing Approach

• Serum creatinine is the initial test of choice for eGFR calculation in all patients 2
• Clinical laboratories routinely report eGFR calculated from serum creatinine along with demographic data (age and sex) 1
• The 2021 CKD-EPI creatinine equation without race is now the recommended standard, as advocated by the American Society of Nephrology and National Kidney Foundation 1, 3
• Laboratories should measure serum creatinine using assays calibrated to international standard reference materials with minimal bias compared to isotope-dilution mass spectrometry 2

When to Order Confirmatory Testing with Cystatin C

Add serum cystatin C measurement in specific circumstances when creatinine-based eGFR may be inaccurate: 1, 2

• eGFR 45-59 mL/min/1.73 m² without albuminuria or other markers of kidney damage - this is the most important indication for confirmatory testing 2, 4
• Extremes of muscle mass (very low or very high) 2, 5
• Extremes of body size 6
• Severe malnutrition or obesity 7
• Diseases affecting muscle mass (paraplegia, amputations) 7
• When more precise GFR estimation affects clinical decision-making (drug dosing, chemotherapy eligibility, kidney donation evaluation) 5

The Combined Creatinine-Cystatin C Equation

• When cystatin C is measured, use the CKD-EPI creatinine-cystatin C equation (eGFRcr-cys) for improved accuracy 1
• This combined equation increases precision and reduces racial and ethnic bias compared to creatinine alone 1
• The combined equation is more accurate than either marker alone but requires both tests 2, 5

Common Pitfalls to Avoid

Do not rely on serum creatinine concentration alone - always use it with an estimating equation 2

Recognize situations where creatinine-based eGFR is less accurate: 8, 9

• Recent changes in kidney function (acute settings)
• Extremes of age (very young or very old)
• Pregnancy
• Severe liver disease
• Recent consumption of cooked meat (can transiently elevate creatinine)

Understand that eGFR >60 mL/min/1.73 m² may not be reported as a specific number by some laboratories due to decreased accuracy at higher GFR levels 10

Measured GFR (Gold Standard)

• Reserve measured GFR using exogenous filtration markers (iohexol, iothalamate, DTPA) for situations requiring the most accurate assessment 2, 5
• Indications include: kidney donor evaluation, clinical trials, when eGFR equations are known to be inaccurate, and when treatment decisions critically depend on precise GFR knowledge 5
• Measured GFR is not practical for routine clinical use due to time, cost, and complexity 11, 12

Practical Algorithm

1. Start with serum creatinine → laboratory automatically reports eGFR using 2021 CKD-EPI equation 1, 5
2. If eGFR 45-59 mL/min/1.73 m² without albuminuria → add cystatin C for confirmation 2, 4
3. If extremes of muscle mass or body composition → add cystatin C 5
4. If critical treatment decisions depend on precise GFR → consider measured GFR 5