The sex difference in plasma cystatin C is age-dependent: a systematic review and meta-analysis.
Filip Landgren, Bertil Kågedal, Eva Landberg
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In 30 seconds
This systematic review and meta-analysis examined sex differences in plasma cystatin C among healthy adults and how they vary with age, with pediatric data reviewed qualitatively. Across 21 studies and more than 46,000 healthy adults, men had higher cystatin C concentrations than women in younger and middle-aged adults: the pooled male-to-female ratio was 1.0860 (95% CI 1.0587-1.1133; p < .0001). The difference was smaller in adults aged 60 years or older (M/F ratio 1.0338, 95% CI 1.0132-1.0544), and meta-regression showed attenuation with increasing age.
Key findings
- In adults aged 60 years or younger, men had 8.6% higher cystatin C concentrations than women (pooled M/F ratio 1.0860, 95% CI 1.0587-1.1133; p < .0001).
- Among adults aged 60 years or older, the sex difference was attenuated (M/F ratio 1.0338, 95% CI 1.0132-1.0544).
- Across adult subgroups, meta-regression found age-related attenuation of the sex difference (β = -0.0011 per year).
- The qualitative pediatric review found a 12-15% sex difference (men > women) emerging during adolescence.
Why it matters
Cystatin C-based GFR estimates may be affected by sex differences that change with age. The findings highlight a potential source of inconsistency between equations that include a uniform sex adjustment and those that do not. Recognising this age-related pattern is relevant when interpreting cystatin C-based estimates and when developing equations intended to reflect differences across the life course.
What to keep in mind
Between-study heterogeneity was substantial (I² = 98% in younger adults, 76% in older adults), potentially reflecting differences in populations and analytical methods.