Abstract
BACKGROUND: Physical dysfunction is a preclinical stage of disability in older adults, linked to severe adverse outcomes such as death and hospitalization. Maximal tubular reabsorption of phosphate (TmP/GFR), as a key biomarker of phosphate metabolism, may be related to physical dysfunction, but this relationship has not yet been explored. METHODS: Using data from the Rugao Longitudinal Ageing Study (RLAS), longitudinal logistic regression was employed to explore the relationship between abnormal TmP/GFR and physical dysfunction. For validation, the UK Biobank dataset was combined, and mendelian randomization (MR) was conducted to investigate causality. The maximal phosphate reabsorption was assessed using TmP/GFR, while physical dysfunction were evaluated through grip strength and the Timed Up and Go (TUG) test. RESULTS: During the four-year follow-up, 89 (13.55%) and 279 (40.85%) participants were identified as having a new onset of decreased grip and TUG. The abnormal TmP/GFR population had a significantly higher risk of decreased grip (OR 2.03, 95% CI 1.20-3.49) and decreased TUG (OR 1.49, 95% CI 1.05-2.12). MR analysis demonstrated the causal effect of TmP/GFR dysfunction population had significantly lower grip and lower walking speed. CONCLUSION: This study first identifies abnormal TmP/GFR as a novel biomarker of physical dysfunction in older adults. Additionally, its causal relationship further substantiates the reliability of this finding. Abnormal TmP/GFR enables early detection of physical dysfunction, facilitating the prevention of severe adverse outcomes.