Should ADPKD Patients Be Screened for Hidden Aneurysms?

Pam Harrison

August 01, 2019

For patients with polycystic kidney disease, screening for brain aneurysms can identify hidden lesions, although knowing that a patient has an aneurysm does not change their management, nor does that fact affect screening recommendations, a single-center review suggests.

"Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of bilateral kidney cysts and extrarenal abnormalities including intracranial aneurysms.... Whether selective or widespread screening for unruptured intracranial aneurysms is indicated remains controversial," Irina M. Sanchez, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues report in an article published online in the Clinical Journal of the American Society of Nephrology.

They found that brain aneurysms were detected during presymptomatic screening in 9% of patients with ADPKD, more frequently in those with a history of hypertension and smoking.

Very few patients experienced aneurysmal ruptures, but the overall rupture rate was approximately five times higher than in the general population.

"Our approach has been to recommend screening for patients with ADPKD who have a family history of aneurysm. We also recommend screening to patients with ADPKD before major elective surgeries (including transplantation), those with high risk occupations [in whom rupture would place the lives of others at risk], and those who after being properly informed on the available data wish to be screened for reassurance," said senior author Vicente Torres, MD, PhD, also of the Mayo Clinic, in a press release issued by the American Society of Nephrology.

"We educate our patients on the importance of correcting conditions that have been associated with aneurysmal development and/or rupture, particularly smoking and inadequately controlled hypertension. The results of our study do not provide a reason for changing our current approach," Torres added.

In an accompanying editorial, Ivana Kuo, PhD, assistant professor of medicine, Loyola University School of Medicine, Chicago, Illinois, and Arlene Chapman, MD, professor of medicine, the University of Chicago, in Illinois, say: "This report provides some incremental confirmatory information regarding the increased frequency of intracranial aneurysm, the traditional characteristics of intracranial aneurysm in ADPKD similar to the general population, and a significant need for more mechanistic studies to determine how central a role [various proteins] play in intracranial aneurysm formation."

Certain Risk Factors for Aneurysms Identified

The researchers reviewed 3010 medical records of patients with polycystic kidney disease who were evaluated at the Mayo Clinic between 1989 and 2017.

A total of 812 patients underwent screening with magnetic resonance angiography (MRA) despite the fact that they had no neurologic symptoms.

An aneurysm was identified in 9% of patients who underwent screening.

During a mean follow-up of 9 years, "none of the 94 intracranial aneurysms detected by presymptomatic screening ruptured," the authors note.

For only seven patients, the aneurysm was repaired, either with surgical clipping or coil embolization, they add.

Certain risk factors for intracranial aneurysm were identified. For example, 37% of patients who were identified as having an aneurysm on MRA screening reported a family history of either intracranial aneurysm or subarachnoid hemorrhage, vs 18% of those for whom no aneurysm was detected on screening (P < .001).

Patients who were identified as having an intracranial aneurysm were also more likely to be hypertensive and to report a history of smoking than those who did not have an aneurysm.

There were no differences in sex, age, race, or genotype between patients with and those without an aneurysm, the researchers note.

"Most aneurysms were small," they add; the median diameter was 4 mm.

Of the aneurysms identified on MRA, 85% were located in the anterior circulation.

Rupture Rate in ADPKD Is Five Times That of General Population

During a mean follow-up of 8 years, the investigators identified de novo aneurysms in five patients in whom an aneurysm had been previously detected. Again, none of these aneurysms had ruptured.

Among patients for whom there was no evidence of an aneurysm on initial screening and who underwent additional MRA testing, three developed an aneurysm during the follow-up period; two patients for whom no aneurysm was detected on initial screening suffered a rupture.

The investigators point out that the overall rupture rate in their ADPKD cohort was approximately five times higher than in the general population.

"At present, our preference continues to be targeted presymptomatic MRA (or computer tomographic angiography) screening of patients with familial history of documented aneurismal rupture or unruptured intracranial aneurysm," they write.

"The results of our study do not provide a reason for changing our current approach," they conclude.

Target Prescreening to Those at Risk; Patient Encourages Participation

In their editorial, Kuo and Chapman say: "Proper identification of risk factors for intracranial aneurysm formation in ADPKD is important and can allow for targeted patient screening and risk factor reduction."

This information is vital, they add, given the significant morbidity and mortality associated with intracranial aneurysm rupture in these patients.

In a written perspective, Kevin Fowler, who is an ADPKD patient, agrees.

Fowler points to ways in which the global ADPKD patient community can be activated. For example, the formation of the PKD Outcomes Consortium has successfully identified total kidney volume as a prognostic biomarker for the community of ADPKD patients with both the US Food and Drug Administration and the European Medicines Agency.

"This biomarker has resulted in one upstream treatment with the potential of more to follow," Fowler writes.

"This powerful message of hope needs to be understood by the patient community while specifying the roles and responsibilities of ADPKD patients to accelerate kidney health," he concludes.

Torres reports receiving grants from Otsuka Pharmaceuticals, Palladio Biosciences, Acceleron Pharma, Regulus Therapeutics, Vertex Pharmaceuticals, Sanofi Genzyme, Blueprint Medicines, and Mironid. The editorialists have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online July 5, 2019. Full text, Editorial

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