Cystatin C is a small protein filtered by the kidneys whose blood level reflects glomerular filtration with much less dependence on muscle mass than creatinine. That makes cystatin C-based eGFR especially useful when creatinine is likely to mislead, and the combined equation is the most accurate estimate available without a measured GFR study.
How it works
Both equations are the 2021 race-free CKD-EPI forms. The cystatin C-only equation scales a base rate by how far cystatin C sits above or below a reference of 0.8 mg/L, then applies age and sex factors:
eGFR(cys) = 133 × min(Scys/0.8, 1)^-0.499
× max(Scys/0.8, 1)^-1.328
× 0.996^age
× (0.932 if female)The combined equation uses both markers, with creatinine handled through sex-specific kappa and alpha constants, and is the most accurate of the three CKD-EPI estimates.
Why cystatin C provides a different signal to creatinine
Creatinine is a breakdown product of creatine phosphate in muscle. Its serum level depends not only on kidney function but on muscle mass, diet (high meat intake transiently raises creatinine), and tubular secretion. In individuals at the extremes of muscle mass — very muscular athletes, frail elderly, amputees, individuals with liver disease reducing creatinine synthesis — the creatinine-based eGFR can be misleading in either direction.
Cystatin C is a cysteine protease inhibitor produced at a fairly constant rate by all nucleated cells. Its production is largely independent of muscle mass and diet, and it is freely filtered at the glomerulus and catabolised by tubular cells without secretion. That makes its serum level a more direct reflection of filtration. However, cystatin C can be elevated by high-dose corticosteroids, thyroid dysfunction (hyperthyroidism lowers it, hypothyroidism raises it), and inflammation — so it is not perfectly unaffected by non-GFR factors.
The combined equation, which uses both markers, is more accurate in most individuals than either alone because the two markers tend to have complementary error profiles.
The 2021 race-free revision
The CKD-EPI equations were revised in 2021 specifically to remove the race coefficient that had been present in the 2009 versions. The original race coefficient added approximately 16% to the eGFR estimate for individuals categorised as Black, based on average differences in creatinine levels observed in the original derivation cohort. The coefficient was removed after consensus that race is not a reliable biological variable and that its inclusion may have contributed to underdiagnosis of CKD in Black patients. This tool implements the 2021 equations without any race term.
KDIGO GFR categories
| Stage | eGFR (mL/min per 1.73 m²) | Description |
|---|---|---|
| G1 | ≥ 90 | Normal or high |
| G2 | 60–89 | Mildly decreased |
| G3a | 45–59 | Mildly to moderately decreased |
| G3b | 30–44 | Moderately to severely decreased |
| G4 | 15–29 | Severely decreased |
| G5 | < 15 | Kidney failure |
CKD staging requires the reduced eGFR or kidney damage markers to be present for more than three months. A single low eGFR value is not sufficient to diagnose CKD.
When to use each equation
- Creatinine-only eGFR — appropriate for routine CKD monitoring in individuals with typical muscle mass and no factors that would distort creatinine.
- Cystatin C-only eGFR — appropriate when creatinine is suspected to be unrepresentative, or when a creatinine result is unavailable.
- Combined creatinine + cystatin C — the most accurate estimate and recommended when confirming CKD before high-stakes decisions: transplant evaluation, nephrotoxic chemotherapy dosing, or changing management based on a borderline eGFR.
Use this tool as a clinical decision support input; confirm with a specialist before acting on the result in high-stakes situations.