In Women with ADPKD, Aneurysm Risk Increases after Age 50

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An analysis of a large cohort of patients with autosomal-dominant polycystic kidney disease (ADPKD) adds new knowledge about risk factors for intracranial aneurysm (IA), including an increase in IA risk for women after menopause, according to a pre-proof paper in Nephrology Dialysis Transplantation.

The cross-sectional, population-based study included 2449 patients with ADPKD (median age, 55 years) from 26 nephrology centers in western France. On genetic analysis in 2386 patients, 67.6% had PKD1 pathogenic variants, and 19.0% had PKD2 pathogenic variants. The researchers analyzed the frequency of diagnosis of ruptured and unruptured IA, along with risk factors for this vascular complication.

At the time of enrollment, 4.65% of patients had previously been diagnosed with IA, ruptured or unruptured. Nearly one-half of patients had a positive family history of IAs. Aneurysms occurred at all stages of chronic kidney disease; most were small, saccular, and located in the anterior circulation. More than one-fourth of patients (26.3%) had multiple IAs.

Cumulative probability of IA diagnosis increased from 1.3% at age 40 to 3.9% at age 50, to 6.2% at age 60, and to 8.1% at age 70. Probabilities of ruptured aneurysm were 0.9%, 1.8%, 2.6%, and 3.2%, respectively.

In patients younger than 50 years old, IA risk was similar for men and women. After 50, however, IA risk was substantially higher in women: up to 10.8% compared with 5.4% in men. The frequency of IA diagnosis was more than twice as high in patients with PKD2 pathogenic variants compared with PKD1 variants. In addition to female sex and PKD1 genotype, hypertension before age 35 and smoking were independent risk factors for diagnosed IA.

Patients with ADPKD are at high risk of IA. Risk factors for IA have important implications for screening using magnetic resonance imaging. In previous reports, a personal or family history has been the main risk factor for IA.

The new finding demonstrates the “complex and multifactorial” determinants of IAs in a large population of patients with ADPKD receiving real-life clinical care. Women appear more likely to be diagnosed with ruptured or unruptured IAs, particularly after age 50. The investigators note, “This parallels observations made in the non-ADPKD population and suggests a possible protective role of estrogens” [Lefèvre S, et al. Diagnosis and risk factors for intracranial aneurysms in autosomal polycystic kidney disease: A cross-sectional study from the Genkyst cohort. Nephrol Dial Transpl, published online ahead of print February 2, 2022. doi: 10.1093/ndt/gfac027;].