Does elevated cystatin C with normal UACR indicate reduced kidney filtration?

Reduced cystatin C–based eGFR and normal albumin excretion are not contradictory. Together, they can describe reduced filtration with an A1/non-albuminuric phenotype, provided the abnormality is persistent and interpreted in clinical context.

Filtration and CKD classification

• Elevated cystatin C with reduced eGFRcys is a well-supported indicator of lower GFR. The CKD-EPI 2012 cystatin C equation had 84.6% of estimates within 30% of measured GFR in validation; in a Swedish iohexol-GFR cohort, 82.5% were within 30% and 58.3% within 10%.
• A UACR <30 mg/g is KDIGO A1 (“normal to mildly increased”) albuminuria. It describes albumin excretion, not whether CKD is present.
• Persistent eGFR <60 mL/min/1.73 m² for >3 months establishes CKD regardless of UACR. With UACR <30 mg/g, this is appropriately termed non-albuminuric CKD.

Mechanistic and interpretive considerations

• Cystatin C is not exclusively determined by filtration. Systemic glucocorticoids and hyperthyroidism can increase cystatin C, making eGFRcys falsely low; hypothyroidism can have the opposite effect. Severe inflammation and catabolic states can also complicate interpretation.
• Therefore, discordance between eGFRcys, creatinine-based eGFR, and the clinical picture warrants review of medications, thyroid status, and systemic illness. Combined creatinine–cystatin C eGFR improves diagnostic/staging accuracy; measured GFR is appropriate when precision would alter a high-stakes decision.

Clinical implications

• A normal UACR does not imply negligible risk: risk rises as eGFR declines even without albuminuria, while albuminuria adds further risk at a given eGFR. Cardiovascular risk may rise at UACR values above approximately 10 mg/g, even below the 30-mg/g threshold.

Bottom line

• The claim is supported: reduced eGFRcys generally indicates reduced filtration, and normal UACR identifies an A1/non-albuminuric phenotype rather than excluding CKD. Confirmation with repeat testing over >3 months is essential.