Extracerebral vascular phenotype in autosomal dominant polycystic kidney disease

Thibault Wallez, Nathalie Demoulin, Yves Pirson Published in the journal : July 2018 Category : Mémoires de Recherche Clinique

Summary :


Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 or PKD2 mutations, is the most common inherited kidney disease. Intracranial aneurysms (ICA) and mitral valve prolapses are well-known vascular complications in ADPKD patients. Other reported vascular manifestations include thoracic aortic aneurysms and dissections (TAAD) and cardiomyopathies (CMP).



We assessed the extracerebral vascular phenotype associated with ADPKD in two ways: (i) exhaustive description of families with at least two members presenting such a phenotype; (ii) prevalence study of thoracic aortic aneurysms (aortic diameter cut-off of 36mm and 38mm in women and men, respectively) and CMP (left ventricular idiopathic dilated cardiomyopathy and hypertrophic obstructive cardiomyopathy).



We identified six families with at least two members presenting with extracerebral vascular phenotype. The first family (PKD1) had one member with thoracic aortic aneurysm (TAA) and popliteal aneurysm and another who died because of aortic dissection. The second family (PKD2) had four members who presented a cerebrovascular accident, two who presented transient ischemic attacks, one who presented TAA, and one who presented aortic dissection. The third family (PKD1) had one member with TAA and subclavian aneurysm and one with TAA. One family (PKD1) had three members with TAA and two others with TAA. We also studied two other families (PKD1 and absence of mutation) involving a person with aortic dissection. In total, six families had at least two members with TAAD’s. All the patients with these vascular phenotypes had ADPKD. The limited number of cases did not permit a genotype-phenotype correlation. After reviewing the echocardiography protocols of 508 patients (out of a cohort of 825), we found an increased prevalence of TAAD (14.9%, 3.2 times more than in the general population). Males, elderly patients, taller patients, and those with poorer renal function had statistically wider thoracic aorta diameters. We initially found six patients with CMP based on ultrasound criteria, but none of these cases were potentially related to ADPKD. The limitations of our study include its retrospective nature, the incomplete access to patients’ medical data, and the use of arbitrary aortic root diameter cut-offs instead of z-scores.



ADPKD is associated with an increased prevalence of TAAD’s, and there seem to be a phenotype accumulation within families. This is at least partly explained by renal failure. We did not find any association between ADPKD and CMP. These results need to be confirmed in larger prospective studies.