Age-dependent sex differences in acute kidney injury among patients with chronic kidney disease

Patients with chronic kidney disease (CKD) are susceptible to acute kidney injury (AKI), which worsens clinical prognosis. Sex differences in AKI incidence and subsequent kidney prognosis remain uncertain in CKD. This multicenter, retrospective cohort study analyzed outpatients with non-dialyzed CKD. Using Cox regression models, AKI incidence was compared between sexes. The risk of kidney replacement therapy (KRT) initiation from 60 days after AKI onset was compared among those who developed AKI. Interaction analyses assessed whether sex differences vary by age. Among 14,552 outpatients (38.5% women), mean age and eGFR were 69 years and 37 mL/min/1.73 m 2 , respectively. Over a median follow-up of 2.5 years, 2,046 developed AKI, with a higher risk in men than in women (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.03–1.26). This difference was most pronounced in individuals aged ≤ 64 years (HR, 1.35; 95% CI, 1.11–1.64) and attenuated in older groups ( P interaction =0.02). Among 1,661 patients followed after AKI, men had an increased risk of KRT initiation (HR: 1.79; 95% CI: 1.34–2.40), consistently most pronounced in younger individuals ( P interaction =0.03). These findings suggest an age-dependent disadvantage for men compared to women in both the incidence and prognosis of AKI among patients with CKD.