Interpreting Serum Creatinine and Assessing Kidney Function with eGFR
Use a validated GFR estimating equation—specifically the 2021 CKD-EPI equation without race—rather than relying on serum creatinine alone, because creatinine values profoundly underestimate renal impairment, particularly in elderly patients and those with low muscle mass. 1, 2
Why Serum Creatinine Alone Is Inadequate
Serum creatinine significantly underestimates renal insufficiency because it varies with age, sex, muscle mass, race, and diet—a "normal" creatinine of 1.2 mg/dL may represent a GFR of 110 mL/min in a young adult but only 40 mL/min in an elderly patient. 1, 3
By the time serum creatinine rises noticeably, GFR has already declined by at least 40%, making it a late indicator of kidney dysfunction. 3
Among patients with normal serum creatinine measurements, one in five has asymptomatic renal insufficiency when assessed by calculated creatinine clearance. 3
The upper limit of normal for serum creatinine is approximately 1.4 mg/dL (124 μmol/L), but this threshold fails to detect early kidney disease in many populations, especially elderly women and those with reduced muscle mass. 1
Recommended Approach: Use eGFR Equations
For CKD Diagnosis and Staging
The 2021 CKD-EPI equation without race is the current standard for adults, providing more accurate GFR estimates than older equations and eliminating race-based adjustments that perpetuate health disparities. 1, 2
Clinical laboratories should automatically report eGFR (rounded to the nearest whole number, expressed as mL/min/1.73 m²) whenever serum creatinine is measured, with values <60 mL/min/1.73 m² flagged as low. 1, 2
For initial assessment in adults, use creatinine-based eGFR (eGFRcr) as the first-line test. 2
For confirmation when eGFRcr is 45-59 mL/min/1.73 m² without other markers of kidney damage (such as albuminuria), add cystatin C to calculate combined eGFRcr-cys, which improves accuracy and correctly reclassifies many patients. 1, 2, 4
For Medication Dosing Decisions
Use the Cockcroft-Gault formula to estimate creatinine clearance (CrCl in mL/min, not indexed to body surface area) because most drug dosing studies and package inserts reference this equation: CrCl = [(140 - age) × weight kg] / [72 × serum creatinine mg/dL] × 0.85 if female. 3
The Cockcroft-Gault formula is specifically intended for drug dosing, not for CKD diagnosis or staging—using normalized eGFR (mL/min/1.73 m²) for medication dosing leads to underdosing in larger patients and overdosing in smaller patients. 3
For obese patients (BMI ≥30 kg/m²), use the mean of actual and ideal body weight in the Cockcroft-Gault equation to improve accuracy. 3
Laboratory Standards for Accuracy
Laboratories must measure serum creatinine using assays calibrated to isotope-dilution mass spectrometry (IDMS) reference methodology, with precision (coefficient of variation <2.3%) and desirable bias (<3.7%). 1, 2
Use enzymatic methods to assay creatinine where possible, as the Jaffe method overestimates serum creatinine by 5-15% compared to enzymatic methods. 1, 3
Report serum creatinine values to two decimal places (e.g., 0.75 mg/dL, not 0.8 mg/dL) to enable accurate eGFR calculation. 2
When cystatin C is measured, measure creatinine on the same sample to enable calculation of combined eGFRcr-cys. 1
Clinical Situations Requiring Alternative Approaches
Consider cystatin C-based or combined creatinine-cystatin C equations when there are extremes of muscle mass, body weight, severe malnutrition, obesity, advanced cirrhosis, cancer, vegetarian diet, or paraplegia/quadriplegia. 1, 2
For drugs with narrow therapeutic indices (vancomycin, aminoglycosides, lithium, digoxin, chemotherapy), consider cystatin C-based equations or measured GFR using exogenous markers (inulin, iohexol, ¹²⁵I-iothalamate) to achieve higher precision. 2, 3
Measured GFR (mGFR) using exogenous filtration markers should be considered when precise GFR measurement is critical for clinical decision-making, such as in glomerular diseases requiring immunosuppression, kidney transplant evaluation, or rapidly changing kidney function. 1, 2
Interpreting eGFR Values
eGFR ≥90 mL/min/1.73 m² represents normal kidney function (Stage 1 CKD only if kidney damage is present, such as albuminuria). 3
eGFR 60-89 mL/min/1.73 m² represents mildly decreased function (Stage 2 CKD if kidney damage is present). 3
eGFR <60 mL/min/1.73 m² represents loss of half or more of normal kidney function and is associated with increased risk for cardiovascular events and CKD complications—this threshold defines CKD regardless of other markers. 1, 3
eGFR 45-59 mL/min/1.73 m² (Stage 3A CKD) without albuminuria should be confirmed with cystatin C to avoid overdiagnosis, as combined creatinine-cystatin C equations correctly reclassify 16.9% of these patients as having eGFR ≥60 mL/min/1.73 m². 1, 4
eGFR 30-44 mL/min/1.73 m² (Stage 3B CKD) requires dose adjustment for all renally cleared medications and warrants nephrology referral. 3
eGFR 15-29 mL/min/1.73 m² (Stage 4 CKD) requires preparation for kidney replacement therapy and careful management of uremic complications. 3
eGFR <15 mL/min/1.73 m² (Stage 5 CKD) represents kidney failure requiring dialysis or transplantation. 3
Common Pitfalls and How to Avoid Them
Never use serum creatinine alone to assess kidney function—the National Kidney Foundation explicitly states this should not be done, as it markedly underestimates renal impairment. 1, 3
Do not use race in eGFR computation—the 2021 CKD-EPI equation without race should be implemented immediately to eliminate health disparities. 1
Do not use MDRD or CKD-EPI equations for medication dosing—these provide GFR indexed to body surface area (mL/min/1.73 m²), whereas drug dosing requires absolute clearance (mL/min) from Cockcroft-Gault. 3
Do not use Cockcroft-Gault for CKD diagnosis or staging—it systematically underestimates GFR in elderly patients and is intended only for medication dosing. 3
Recognize that all creatinine-based equations overestimate true GFR by 10-40% because creatinine is both filtered and secreted by renal tubules, with greater overestimation as kidney function declines. 3
eGFR equations are valid only at steady state—in acute kidney injury or rapidly changing renal function, use serial serum creatinine measurements and consider measured GFR. 1
For values >60 mL/min/1.73 m², laboratories should report ">60 mL/min/1.73 m²" rather than a precise figure, as accuracy is suboptimal at higher GFR levels. 5
Practical Implementation Algorithm
Order serum creatinine with automatic eGFR reporting using the 2021 CKD-EPI equation without race. 2
If eGFR ≥60 mL/min/1.73 m²: kidney function is adequate for most purposes; no further testing unless clinical suspicion for kidney disease (check for albuminuria). 2, 3
If eGFR 45-59 mL/min/1.73 m² without albuminuria: add cystatin C to calculate combined eGFRcr-cys for confirmation before diagnosing CKD. 1, 2
If eGFR <45 mL/min/1.73 m² or any eGFR <60 with albuminuria: CKD is confirmed; stage appropriately, adjust medications, and consider nephrology referral. 1, 3
For medication dosing: calculate Cockcroft-Gault creatinine clearance (use mean of actual and ideal body weight if obese), and adjust doses per package insert. 3
For narrow-therapeutic-index drugs or extreme body composition: consider cystatin C-based equations or measured GFR. 2, 3