Risk Factors for Intracranial Aneurysms in Asymptomatic Patients with Autosomal Dominant Polycystic Kidney Disease: Who Needs Screening?A Systematic Review and Meta-Analysis

Introduction: Patients with autosomal dominant polycystic kidney disease (ADPKD) have been identified to have a significantly increased risk of developing intracranial aneurysms (IA) and of IA rupture. Given the high morbidity and mortality of ruptured IA even with appropriate intervention, there is a need to understand which ADPKD patients need to be screened for IA. The objective of this systematic review and meta-analysis is to identify risk factors associated with IA detection during screening of asymptomatic ADPKD patients.

Methods: PubMed, Embase, Google Scholar, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and clinicaltrials.gov were searched for studies reporting the prevalence of IA amongst ADPKD patients. Three reviewers assessed the eligibility of retrieved studies following the PRISMA guidelines. Data extraction was performed by three reviewers with an additional data-checking step. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using the OpenMetaAnalyst software using a random-effects model.

Results: Twenty-eight studies on ADPKD with 6,140 total patients were identified for analysis. The overall prevalence of IA in this meta-analysis was 12.9% (95% CI 10.5-15.6%). Risk factors associated with statistically significantly increased odds for IA including female sex (OR 1.622, 95% CI 1.366, 1.925), family history of IA or subarachnoid hemorrhage (SAH) (OR 2.159, 95% CI 1.673, 2.786), stage ≥ 3 chronic kidney disease (CKD) (OR 2.554, 95% CI 1.843-3.538), and hypertension (OR 1.431, 95% CI 1.063, 1.926). Multiple aneurysms were found in 74 of 308 (25.3%) patients with IA in studies that reported multiple aneurysms as an outcome.

Conclusion : The results of our meta-analysis suggest increased risk of IA in patients with ADPKD who are female, have a family history of IA or SAH, have hypertension, or have moderate or more severe CKD. These patients may benefit from screening for IA early in treatment or at time of diagnosis even if neurologically asymptomatic. Cost-benefit analysis and further studies of natural history are required to better understand the additional risk of morbidity and mortality associated with IA in ADPKD patients.