Should abnormal cystatin C results be attributed to age alone?

Normal kidney aging involves structural and functional change, but these changes do not make an abnormal cystatin C result automatically benign—particularly in a 70-year-old in whom kidney-risk assessment may affect medication dosing and cardiovascular risk management.

Aging-related kidney changes

• Normal aging is associated with nephron loss: among healthy living donors, mean nonsclerotic glomerular number fell from about 991,000 per kidney at ages 18–29 to 520,000 at ages 70–75—approximately a 48% lower count. Glomerulosclerosis also increases with age.
• Average GFR and renal functional reserve decline with age, although variability is large. In small inulin-clearance studies, healthy older adults could increase GFR after amino-acid infusion, but had lower baseline and stimulated GFR and a smaller reserve response than younger adults.

Interpreting cystatin C and eGFRcys

• An above-range cystatin C or low eGFRcys should not be dismissed as age alone. Elevated cystatin C produces a lower eGFRcys by definition, but cystatin C reflects more than filtration.
• Independent of GFR, cystatin C may be increased by adiposity/obesity, smoking, chronic inflammation, and glucocorticoid exposure; hyperthyroidism may also raise it. Thus, discordant or abnormal results can represent reduced filtration, altered cystatin C production/handling, or both.
• A single low eGFRcys does not establish chronic kidney disease. CKD classification requires persistence for ≥3 months; a persistent GFR below 60 mL/min/1.73 m² remains clinically important in older adults.

Clinical implications

• Repeat kidney testing, assess urine albumin-to-creatinine ratio, and consider combined creatinine–cystatin C eGFR for categorization. When estimates remain discordant or decisions depend on precision, measured GFR may be appropriate.

Bottom line

• Aging plausibly contributes to nephron loss and lower filtration reserve, but it is not an adequate stand-alone explanation for abnormal cystatin C or eGFRcys. Persistent abnormalities merit assessment for kidney disease, albuminuria, acute illness, and non-GFR influences.