Can a single cystatin C–based eGFR be influenced by non-GFR factors?

A cystatin C–based eGFR is often useful, particularly when creatinine may be misleading, but it remains an estimate rather than a direct filtration measurement. In a 70-year-old man, an isolated low eGFRcys should therefore be interpreted alongside clinical status, prior kidney results, urine albumin findings, and potential transient influences.

Interpretation of a single eGFRcys

• Thyroid dysfunction and glucocorticoid exposure can alter cystatin C independently of true GFR. In an outpatient study of 5,595 adults, systemic glucocorticoid use was associated with higher cystatin C even after adjustment for iohexol-measured GFR, with an apparent dose-related effect.
• Inflammation and acute illness are plausible contributors, but the evidence is less consistent: a systematic review found limited contemporaneous measured-GFR data and variable results.
• Normal within-person variability also matters. Cystatin C biological variation is approximately 3–5%; reported reference-change values are about 13–14%, and KDIGO reports eGFRcys reference-change values of 14–20% in people with CKD.
• Higher adiposity and smoking are additional potential non-GFR influences on cystatin C.

Mechanistic and practical implications

• Because eGFRcys is calculated from serum cystatin C, factors that change cystatin C production, metabolism, or its relation to filtration can shift the reported eGFR without an equivalent change in measured GFR.
• During steroid treatment, thyroid disease, acute illness, or possible inflammatory activity, an isolated eGFRcys should not automatically be interpreted as a stable decline in kidney filtration. When the result would affect a consequential decision, combined creatinine–cystatin C estimation or exogenous-marker measured GFR can be appropriate.

Chronicity

• CKD requires kidney structural or functional abnormalities persisting for at least 3 months. A single reduced eGFR cannot establish CKD, since it may reflect acute kidney injury, transient illness, or expected biological/analytical variation.
• NICE advises repeating a newly detected eGFR below 60 mL/min/1.73 m² within 2 weeks to assess for acute deterioration, with later confirmation or prior records needed to establish persistence.

Bottom line

• The claim is well founded: single eGFRcys values can be affected by non-GFR factors and ordinary variation, while CKD classification requires persistent abnormality over time—not one abnormal result.