Vascular complications in autosomal dominant polycystic kidney disease

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Relentless cyst growth substantially enlarges both kidneys and culminates in renal failure. Patients with ADPKD also have vascular abnormalities; intracranial aneurysms (IAs) are found in ∼10% of asymptomatic patients during screening and in up to 25% of those with a family history of IA or subarachnoid haemorrhage. As the genes responsible for ADPKD—PKD1 and PKD2—have complex integrative roles in mechanotransduction and intracellular calcium signalling, the molecular basis of IA formation might involve focal haemodynamic conditions exacerbated by hypertension and altered flow sensing. IA rupture results in substantial mortality, morbidity and poor long-term outcomes. In this Review, we focus mainly on strategies for screening, diagnosis and treatment of IAs in patients with ADPKD. Other vascular aneurysms and anomalies—including aneurysms of the aorta and coronary arteries, cervicocephalic and thoracic aortic dissections, aortic root dilatation and cerebral dolichoectasia—are less common in this population, and the available data are insufficient to recommend screening strategies. Treatment decisions should be made with expert consultation and be based on a risk-benefit analysis that takes into account aneurysm location and morphology as well as patient age and comorbidities.

Figure 1

An aortic aneurysm in a 19-year-old patient with ADPKD. 3D magnetic resonance angiogram showing the ascending aortic aneurysm (arrow). Abbreviation: ADPKD, autosomal dominant polycystic kidney disease. Permission obtained from the American Society of Nephrology © Liu, D. et al. J. Am. Soc. Nephrol. 25, 81–91 (2014).

Figure 2

Right vertebral artery dissection in a 47-year-old patient with ADPKD. a | Angiogram b | 3D rotational angiogram and c | 3T magnetic resonance angiogram showing a spontaneous asymptomatic nontraumatic right vertebral artery dissection (dual arrows) and associated pseudoaneurysm (single arrow) with non-haemodynamically significant stenosis. The patient also had an unruptured intracranial aneurysm (shown in Figure 3). Abbreviation: ADPKD, autosomal dominant polycystic kidney disease.

Figure 3

An unruptured intracranial aneurysm in a 47-year-old patient with ADPKD and distant smoking history. The patient underwent screening for assessment of suitability for transplant. a | 3T magnetic resonance angiograms showing an unruptured 5 mm aneurysm in the anterior communicating artery. b–c | 3D rotational angiograms confirming the presence of the aneurysm. d | 3D rotational angiogram showing the aneurysm after treatment using endovascular coiling. e | Magnetic resonance angiogram showing the stable aneurysm at 3-year follow up. Arrows indicate the position of the aneurysm. Abbreviation: ADPKD, autosomal dominant polycystic kidney disease.

Figure 4

Pkd1 deletion in VSMCs results in abnormal proximal ascending aortic architecture. Ascending aortic sections from 6-month-old mice with (Pkd1^VSMC−) and without (Pkd1^VSMC+) selective deletion of Pkd1 in VSMCs were stained with Verhoeff–Van Gieson. a | Intact elastic fibre architecture in the aorta of a Pkd1^VSMC+ mouse. b–d | Aortic sections from Pkd1^VSMC− mice demonstrate diffuse fragmentation of elastic fibres and increased extracellular matrix deposition. e | Blinded quantitative histologic evaluation of aorta architecture scored by three observers (n = 8). *P = 0.001. Abbreviation: VSMC, vascular smooth muscle cell. Permission obtained from the American Society of Nephrology © Liu, D. et al. J. Am. Soc. Nephrol. 25, 81–91 (2014).

Figure 5

A ruptured intracranial aneurysm in a 46-year-old patient with ADPKD. a | CT scan showing diffuse subarachnoid haemorrhage and hydrocephalus. b | 3 T magnetic resonance angiogram showing the ruptured basilar bifurcation. c | 3D rotational angiography confirmed the presence of a wide-necked aneurysm. d | The aneurysm following treatment using endovascular coiling, which had an excellent result. Abbreviation: ADPKD, autosomal dominant polycystic kidney disease.

Figure 6

Surgical and angiographic techniques for the treatment of intracranial aneurysms. a | Microsurgical clipping. b | Endovascular coiling. c | Stent-supported coiling. d | Flow-diverter therapy.