Study on the physical activity levels and all-cause mortality risk in diabetic kidney disease patients and mediating effect of inflammation

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Objective: To analyze the association between physical activity levels and all-cause mortality risk in patients with diabetic kidney disease (DKD) and to investigate the mediating effect of inflammation. Methods: Based on National Health and Nutrition Examination Survey of America data matched with the National Death Index of America, a prospective cohort was formed, including 59 482 participants from six cycles between 2007 and 2018. After applying inclusion and exclusion criteria, 2 214 DKD patients were selected for the study. Cox proportional hazard regression models were used to analyze the impact of physical activity levels on all-cause mortality risk. The mediating effect of inflammatory markers in the association between physical activity and all-cause mortality risk was explored. Results: There were statistically significant differences in survival curves among different physical activity level groups (P<0.001). As physical activity levels increased, the risk of mortality decreased. Patients in the high physical activity group had a lower mortality risk compared to those in the inactive group (HR=0.64, 95%CI: 0.53-0.78), with a statistically significant difference (P<0.001). Patients with higher physical activity levels had lower levels of inflammation (white blood cell, neutrophil, and C-reactive protein) (P<0.001). White blood cell, neutrophil, C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and the systemic inflammation index (SII) were independent risk factors for mortality in DKD patients (HR>1.00), with higher risk effects observed for the combined indicator lgNLR (HR=2.06, 95%CI: 1.76-2.41) and lgSII (HR=1.44, 95%CI: 1.26-1.64). Mediation analysis showed that physical activity had an indirect effect on all-cause mortality risk through neutrophil, with an effect size of -0.033 (95%CI: -0.052 - -0.002), which was statistically significant (P<0.05), with a mediation effect proportion of 9.75%. Conclusion: Physical activity is a protective factor against all-cause mortality risk in DKD patients, partly through reducing neutrophil levels.