Autosomal dominant polycystic kidney disease (ADPKD) is a renal hereditary disorder associated with increased cardiovascular mortality, due to mutations in polycystin-1 (PC1) and polycystin-2 (PC2) genes. Experimental evidence suggests that polycystins regulate pressure sensing in vascular smooth muscle cells but this remains to be confirmed in humans.

The objective of this study is to evaluate vascular parameters in patients with autosomal dominant polycystic kidney disease.

Carotid artery blood pressures, geometry and function were assessed in 33 non-hypertensive ADPKD patients with preserved renal function and 46 control subjects frequently matched for age, sex and brachial blood pressures, using applanation tonometry coupled with high-resolution echotracking.

Compared to controls, ADPKD patients displayed an increase in aortic and carotid systolic and pulse pressures due to altered cardiovascular coupling (Figure 1A et 1B). Carotid intima-media thickness (Figure 1C) as well as end-diastolic diameter remained unchanged. In addition, aortic and carotid artery stiffness was similar between groups. A genotype/phenotype analysis revealed that, patients with a truncating PKD1 mutation had a lesser intima-media thickness (Figure 2A) than patient with a non-truncating PKD1 mutation, despite similar carotid pulse pressure, leading to a marked increase in circumferential wall stress (Figure 2B).

ADPKD patients exhibit maladaptive arterial remodeling in response to elevated pulse pressure demonstrating the role of polycystins in blood pressure sensing. The paradoxical decrease in arterial wall thickness and associated increase in arterial wall stress in patients with a truncating PKD1 mutation may exacerbate the vascular complications of ADPKD, primarily aneurysms.