How to prepare for the «Cystatin C» test: rules for taking it
Cystatin C is a protein whose level is used to assess the glomerular filtration rate (GFR) of the kidneys. It is increasingly ordered when creatinine «lies»: in people with a large or, conversely, very small muscle mass, in vegetarians, in athletes who take creatine. However, cystatin C has its own influencing factors — hormones, inflammation, smoking — which are worth knowing about before the test. Our editorial team explains how to prepare and how to read the result.
What cystatin C is and why it is better than creatinine
Cystatin C is a small protein, a protease inhibitor, produced by almost all nucleated cells of the body. Its rate of formation is relatively stable. Thanks to its small size it is freely filtered in the glomeruli of the kidneys and then completely absorbed and broken down in the tubules, without returning to the blood.
Therefore the concentration of cystatin C in the blood depends primarily on how well the kidneys filter. When GFR decreases, cystatin C rises. This principle is similar to the creatinine one, but with an important difference: cystatin C is far less dependent on muscle mass and diet.
A study by Shlipak and colleagues (2013) in the New England Journal of Medicine showed that GFR calculated from cystatin C, or from a combination of cystatin C and creatinine, better predicts the risks of death, cardiovascular events and end-stage renal failure than an assessment from creatinine alone.
The most accurate is considered to be the combined formula using both markers. Its effectiveness was demonstrated by Inker and colleagues (2012), and in 2021 an updated version without a race adjustment was proposed. The KDIGO guidelines recommend determining cystatin C when an assessment by creatinine may be unreliable.
Who should have cystatin C tested
The most obvious group is people with atypical muscle mass. In bodybuilders and strength athletes, creatinine is high because of muscle, and the calculated GFR comes out underestimated. In elderly people with sarcopenia, after amputations, with prolonged immobilization — on the contrary, creatinine is low and can mask a real decline in kidney function.
The second group is those whose diet or supplements change creatinine: vegetarians and vegans, people on a high-protein diet, and also athletes who take creatine monohydrate. For them cystatin C gives an independent assessment.
- athletes with a large muscle mass and those who take creatine;
- elderly people, especially with pronounced muscle loss;
- vegetarians and people with an unusual diet;
- patients whose GFR by creatinine is «on the edge» and on which the diagnosis depends;
- patients who need an accurate GFR assessment for drug dosing.
Cystatin C is also useful when the creatinine GFR is close to the threshold of 60 mL/min/1.73 m², on which the establishment of chronic kidney disease depends. KDIGO suggests confirmation with cystatin C in such a situation, so as not to make the diagnosis falsely.
At the same time, cystatin C is not a «universal replacement». It is an additional test, and the doctor chooses it taking into account the specific clinical situation and its availability in the laboratory.
What affects the result
Independence from muscles does not mean independence from everything. The most important known factor is glucocorticoids: prednisolone and similar drugs increase the formation of cystatin C, and GFR by it may turn out underestimated.
The second group is thyroid function. A study by Fricker and colleagues (2003) showed that in hyperthyroidism the level of cystatin C rises, and in hypothyroidism it falls, independently of actual filtration. That is why in thyroid disease or the intake of thyroid hormones the result should be assessed with caution.
| Factor | Effect on cystatin C | Comment |
|---|---|---|
| Glucocorticoids | Increase | GFR may be underestimated |
| Hyperthyroidism, intake of thyroid hormones | Increase | First assess TSH |
| Hypothyroidism | Decrease | GFR may be overestimated |
| Systemic inflammation | Possible increase | Postpone a scheduled test during acute illness |
| Obesity, smoking | Increase in population studies | Take into account during interpretation |
| Meat, creatine, muscle mass | Minimal | The main advantage of the test |
Population studies also link a higher cystatin C with obesity, smoking and elevated inflammation markers. These associations are smaller than the effect of muscle on creatinine, but with an acute infection a scheduled test is better postponed.
Laboratory standardization deserves separate mention. Previously, the results of different methods differed substantially; today there is an international reference material to which modern analyzers are calibrated. Nevertheless, it is better to compare results from different laboratories with caution.
Rules for the test
No special diet is needed for cystatin C, and this is its convenience. However, the test is usually taken together with creatinine, so it is better to follow the stricter rules: in the morning, on an empty stomach, after a normal dinner without a large portion of meat.
The day before, it is worth avoiding exhausting workouts and dehydration. These factors affect cystatin C itself less than creatinine, but if the doctor is going to calculate a combined GFR, both indicators should be obtained under standard conditions.
Be sure to tell the doctor about the intake of glucocorticoids (tablets, injections, prolonged use of inhaled forms in high doses), about thyroid disease and the intake of thyroid hormones. If you have recently had an acute infection, a scheduled test is better postponed until recovery.
Creatine monohydrate need not be discontinued if the goal is precisely to assess GFR by cystatin C — this is one of the test's advantages for athletes. However, if the same test also determines creatinine, the doctor will take the supplement into account or advise a pause.
How GFR by cystatin C is interpreted
The laboratory reports the concentration of cystatin C in milligrams per liter, and GFR is calculated using the CKD-EPI formulas — either from cystatin C alone or in combination with creatinine. It is precisely the calculated GFR, not the absolute concentration, that is used to classify kidney function under KDIGO.
If GFR by creatinine is reduced but by cystatin C is normal, in a muscular person this is most often explained by the effect of muscle mass. The opposite situation — a normal creatinine GFR and a reduced cystatin C one — requires a more careful examination, especially in elderly people.
As with creatinine, a single deviation is not a diagnosis. Chronic kidney disease is established when changes are present for more than three months, taking into account a urine albumin test.
In doubtful cases, when an accurate GFR is critically important, the doctor may order a direct measurement of clearance, for example using iohexol. But for most people the combination of creatinine and cystatin C gives a sufficiently accurate assessment.
Editorial conclusions
Cystatin C is a valuable marker of kidney function for those in whom creatinine is unreliable: athletes with a large muscle mass, people who take creatine, vegetarians and elderly people.
Preparation for the test is simple, but it is important to tell the doctor about glucocorticoids, thyroid state and recent infections, because it is precisely these that distort the result most strongly.
The most accurate assessment is given by a combination of cystatin C and creatinine obtained in one test under standard conditions.
We also recommend reading our materials on preparing for the creatinine test, on preparing for the TSH test and on the safety of creatine for the kidneys.
References
- Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10):932–943.
- Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20–29.
- Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737–1749.
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117–S314.
- Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C. Impact of thyroid dysfunction on serum cystatin C. Kidney Int. 2003;63(5):1944–1947.
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1–150.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
