Increased Risk of Middle Cerebral Artery Aneurysms in Postmenopausal Women with ADPKD: Insights from Attribute-Based Medicine (ABM) with Cross-Classification Based on Sex and Age

Background: The 2024 KDIGO conference emphasized shifting away from a one-size-fits-all model toward individualized CKD care. Women with autosomal dominant polycystic kidney disease (ADPKD) face a heightened risk of intracranial aneurysms (IAs), yet the role of menopause-related hormonal changes in IA susceptibility remains underexplored. Given the global burden of aneurysmal subarachnoid hemorrhage (SAH) and the known impact of estrogen decline on vascular integrity, understanding sex- and age-specific IA risk is essential to improving care for women with ADPKD. Methods: We retrospectively analyzed 519 ADPKD outpatients who underwent MRA screening at a single Japanese center. Patients were cross-classified by sex and age (<50 vs ≥50 years) to assess IA prevalence, rupture history, and aneurysm location. Multivariable logistic regression and Kaplan–Meier analyses identified IA risk factors. Special focus was placed on middle cerebral artery (MCA) aneurysms using a cross-classification approach. Results: IA prevalence was highest in women ≥50 years (31.3%), compared to 19.4% in all women and 16.6% in men. Female sex, advanced CKD (stages IV–V), hypertension, and a family history of IA/SAH emerged as independent risk factors. Notably, women ≥50 years had a tenfold higher risk of MCA aneurysms than women <50 years (40.5% vs 5.9%, OR=10.88, P=0.011). Logistic regression confirmed women ≥50 years as an independent risk group for both IAs (OR=2.11, P=0.006) and MCA aneurysms (OR=4.22, P<0.001). Time-to-event analysis revealed earlier IA development in this subgroup, especially among hypertensive patients. Conclusion: Women ≥50 years with ADPKD represent a high-risk group for intracranial and MCA aneurysms. These findings underscore the importance of menopause-aware screening and prevention strategies. Hormonal and vascular factors likely contribute to IA vulnerability in this group, supporting tailored surveillance protocols to improve cerebrovascular outcomes in women with ADPKD.Attribute-Based Cross-Classification by Sex and Age for Intracranial and MCA Aneurysms in ADPKD