Age- and sex-specific normative values for reticulocyte indices and their relation to early-stage CKM syndrome

BACKGROUND: Reticulocyte-related indices reflect erythropoietic activity and red blood cell maturation and may provide insight into systemic metabolic and inflammatory states. Cardiovascular-kidney-metabolic (CKM) syndrome is a progressive systemic disorder driven by interacting metabolic, renal, and cardiovascular abnormalities. This study aimed to establish age- and sex-specific normative values for reticulocyte-related indices and to explore their cross-sectional associations with early-stage CKM syndrome. METHODS: A total of 5,692 adults aged 20-80 years from the China National Health Survey were included in this cross-sectional study for the final analysis. The Lambda-Mu-Sigma method was used to generate age- and sex-specific smoothed percentiles for reticulocyte indices, including RET# (reticulocyte count), RET% (reticulocyte percentage), LFR (low fluorescence reticulocytes), MFR (medium fluorescence reticulocytes), HFR (high fluorescence reticulocytes), IRF (immature reticulocyte fraction), RET-HE (reticulocyte hemoglobin equivalent), and RPI (reticulocyte production index), with percentile estimates at P1, P5, P25, P50, P75, P95, and P99. Differences across early CKM stages were assessed using one-way analysis of variance, chi-square tests, and analysis of covariance. Receiver operating characteristic analysis was used to evaluate discriminative performance. RESULTS: Reticulocyte-related indices showed significant sex-specific and age-specific variation, generally increasing in younger and middle-aged adults and then plateauing or declining in older adults. Several indices were associated with CKM stage progression. In particular, RET#, RET%, and RPI increased across CKM stages, whereas LFR decreased. ROC analysis showed that RET# provided good discrimination between CKM stage 0 and stages 1-2, with improved performance after adjustment for age and sex. CONCLUSION: Reticulocyte-related indices exhibit distinct age- and sex-specific distributions and are associated with early CKM stage status in this cross-sectional population. These findings provide normative reference data and suggest that reticulocyte indices may serve as exploratory indicators of systemic metabolic status, although prospective studies are needed to establish clinical utility.