Associations Between Sarcopenia, PhenoAgeAccel, and New-Onset AKI: A UK Biobank Study

Background: Sarcopenia, an age-related loss of muscle mass, strength, and function, may impact kidney health. PhenoAgeAccel, a biomarker-based measure of biological aging, reflects aging beyond chronological age. This study investigated the individual and combined effects of sarcopenia and PhenoAgeAccel on acute kidney injury (AKI) risk in the UK Biobank cohort. Methods: This cohort study of 300,791 UK Biobank participants examined the associations of sarcopenia (per EWGSOP2019) and PhenoAgeAccel (biomarker-based) with incident AKI. AKI was identified via ICD-10 codes. Cox models assessed their independent, joint, interactive, and mediating effects, adjusting for demographic, lifestyle, and clinical factors. Results: We excluded 200,832 participants with missing data and 547 with prior AKI, leaving 300,791 for analysis. During follow-up, 15,912 developed AKI. Compared to non-sarcopenia, probable and confirmed sarcopenia were associated with 25% (HR 1.25, 95% CI: 1.20–1.30) and 65% (HR 1.65, 95% CI: 1.37–1.99, P < 0.001) higher AKI risk, respectively. PhenoAgeAccel showed a dose-response with AKI; Q4 had a 2.08-fold higher risk than Q1 (HR 2.08, 95% CI: 1.97–2.19, P < 0.001). Combined sarcopenia and Q4 PhenoAgeAccel had the highest risk (HR 3.26, 95% CI: 2.49–4.26). Additive and multiplicative interactions were significant (RERI 1.97, AP 0.53, synergy index 3.59; all P < 0.001). Mediation analysis showed PhenoAgeAccel mediated 10–16% of the sarcopenia–AKI association. Conclusion: In conclusion, sarcopenia and PhenoAgeAccel were each significantly associated with increased AKI risk, with a dose-response for PhenoAgeAccel. Their combination showed a synergistic effect, highlighting the need to consider both in AKI risk assessment and management.Cumulative Incidence of Acute Kidney Injury Stratified by Sarcopenia Status and Phenotypic Age Acceleration