Cystatin C is a small protein produced by every nucleated cell at a steady rate and filtered by the kidneys. Because it ignores muscle mass, it estimates kidney function more accurately than creatinine, especially in the very muscular, the frail and the elderly.
Standard range versus optimal range
| Framework | Cystatin C value | Source |
|---|---|---|
| Standard lab reference | about 0.5-1.1 mg/L | Common laboratory range |
| Confirmatory test for CKD | combined with creatinine in eGFR | KDIGO guideline |
When it runs high
High cystatin C indicates reduced kidney filtration, with a few non-kidney contributors worth remembering. Even mild elevations predict cardiovascular events and mortality more strongly than creatinine-based estimates in the same people.
- Chronic kidney disease or acute kidney injury
- High dose corticosteroids, which raise production
- Thyroid dysfunction, high in hyperthyroidism
- Obesity and chronic inflammation, modest effects
- Smoking
When it runs low
Low cystatin C reflects good filtration and needs no action. Values below the usual range appear in hypothyroidism and carry no known harm.
- Efficient kidney filtration, the normal state
- Hypothyroidism, modest effect
The muscle-blind kidney marker
Every nucleated cell releases cystatin C at a nearly constant rate, and the kidneys remove it almost exclusively by filtration. That tidy biology removes the great weakness of creatinine, dependence on muscle mass. In a muscular athlete creatinine overestimates kidney disease, and in a frail 80-year-old it underestimates it. Cystatin C reads both correctly, which is why KDIGO recommends it as the confirmatory test when creatinine-based eGFR leaves doubt.
A sharper crystal ball
The 2012 CKD-EPI collaboration showed that equations combining creatinine and cystatin C classify kidney risk better than either marker alone, reclassifying a meaningful share of people out of falsely low eGFR categories. Cystatin C also predicts heart failure and death more strongly than creatinine at equal filtration, probably because it captures vascular and inflammatory burden that creatinine misses.
When to ask for it
Cystatin C earns its cost when the creatinine story does not fit, in amputees, bodybuilders, the very old, those with cirrhosis or severe malnutrition, and anyone whose creatinine eGFR hovers near a treatment threshold. Steroid courses and uncontrolled thyroid disease nudge it, so interpret it after those are accounted for.
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