Serum adropin as a potential renoprotective factor in diabetic kidney disease: evidence from a Chinese elderly cohort and an experimental mouse model.

Introduction: Adropin is an energy homeostasis-related peptide implicated in metabolic and vascular regulation, but its relationship with diabetic kidney disease (DKD) remains unclear. We examined cross-sectional and longitudinal associations between serum adropin and DKD and complemented the human findings with experimental validation in mice. Research design and methods: Participants were drawn from a community-based cohort in Guankou Town, Xiamen, China (2013-2021). The index visit was defined as each participant's first health examination during 2013-2015. Cross-sectional associations with prevalent DKD were evaluated using multivariable logistic regression and restricted cubic spline (RCS) models. Longitudinal associations with incident DKD were assessed using Cox proportional hazards models and RCS. An STZ-induced DKD mouse model was used to assess adropin dynamics during disease progression and the effects of adropin administration. Results: Among 6,896 participants, higher serum adropin was inversely associated with prevalent DKD (adjusted OR per 1-unit increase 0.83 [95% CI 0.71-0.96]). Among participants free of DKD at baseline, 749 incident DKD cases occurred over a median follow-up of 6.09 years; higher baseline adropin was associated with lower incident DKD risk [adjusted HR per 1-unit increase 0.88 (0.85-0.91)]. RCS analyses suggested a largely linear cross-sectional association and a non-linear prospective association. In mice, serum adropin declined during DKD progression, and adropin treatment improved renal injury-related indicators compared with untreated DKD controls. Conclusion: Serum adropin was inversely associated with both prevalent and incident DKD in a community-based cohort, and experimental findings support a potential renoprotective role of adropin.