Cystatin C

A protein filtered by the kidneys that estimates kidney function without depending on muscle mass, which makes it more reliable than creatinine in lean or very muscular people.

What it measures

Cystatin C is a small protein produced by essentially all nucleated cells at a fairly steady rate, filtered freely at the glomerulus and then broken down in the kidney tubules. Blood levels rise as filtration falls, which makes it an estimate of glomerular filtration rate.

The advantage over creatinine is what it does not depend on. Creatinine comes from muscle, so a heavily muscled person can look like they have worse kidney function than they do, and a frail person with little muscle can look deceptively healthy.

Where guidelines place it

KDIGO recommends cystatin C as a confirmatory test when a creatinine based estimate suggests reduced function but there is no other evidence of kidney disease. In practice that is the single most useful moment to order it.

The 2021 CKD-EPI equations include a version using both creatinine and cystatin C, which performs better than either marker alone and is the preferred estimate when both are available.

What raises it besides kidney function

Cystatin C is not perfectly clean either. Thyroid dysfunction, corticosteroid use, high inflammatory states and possibly adiposity can shift it independently of filtration. It is also more expensive and less widely ordered.

The practical read: if you lift heavily, eat a lot of protein, or take creatine, and your creatinine based eGFR looks mildly low, cystatin C is the test that settles the question.

Cystatin C is not a routine recommendation, but it is the follow-up test worth raising with a clinician when a creatinine based estimate does not fit the person. Our eGFR calculator uses the 2021 race-free creatinine equation.

References

  1. Inker LA, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021.
  2. Inker LA, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012.
  3. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013.