Association between infrarenal abdominal aortic aneurysm and autosomal dominant polycystic kidney disease: a case report

Abstracts

A doença renal policística dominante é uma das doenças renais hereditárias mais comuns, podendo apresentar manifestações extrarrenais vasculares de importância clínica, como aneurismas intracranianos, aneurismas aórticos e dissecções arteriais. Relatamos o caso de um paciente masculino, com 66 anos de idade, renal crônico não-dialítico por doença renal policística dominante, com aneurisma de aorta abdominal infrarrenal assintomático, diagnosticado por ultrassonografia de rotina e operado eletivamente com sucesso. A doença renal policística dominante é uma síndrome genética, associada aos genes PDK1 e PDK2 no cromossomo 16. A expressão desses genes na parede dos vasos leva ao seu enfraquecimento, favorecendo a formação de aneurismas. A produção de metaloproteinases pelos túbulos renais também estaria relacionada às doenças vasculares desses pacientes. Tais doenças se apresentam como importantes fatores de mortalidade precoce e morbidade dos portadores de doença renal policística dominante e, como usualmente são assintomáticas, justifica-se o uso de propedêutica armada e tratamento precoce.

Aneurisma aórtico; rim policístico autossômico dominante; insuficiência renal crônica

CASE REPORT

Association between infrarenal abdominal aortic aneurysm and autosomal dominant polycystic kidney disease: a case report

Milton Alves das Neves Junior; Rafael Couto Melo; Adenauer Marinho de Oliveira Goes Junior; Tatiana Rocha Protta; Alexandre Petnys; Edgar Rabboni

Hospital do Servidor Público Municipal, São Paulo, SP, Brazil

Correspondence

ABSTRACT

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary renal diseases, which may present important clinical extrarenal vascular manifestations, such as intracranial and aortic aneurysms and artery dissections. We report the case of a 66-year-old male chronic renal out-of-dialysis patient, with dominant polycystic kidney disease, presenting an asymptomatic infrarenal abdominal aortic aneurysm diagnosed by routine ultrasonography, submitted to successful elective surgery. ADPKD is a genetic syndrome, associated with PDK1 and PDK2 genes on chromosome 16. The expression of these genes in the vessel walls leads to vessel wall weakening, favoring aneurysm formation. In addition, metalloproteinase production by kidney tubules could be related to vascular diseases in ADPKD patients. These are important factors of early mortality and of morbidity in patients with ADPKD, thus the use of equipped propedeutics and early treatment are indicated, as these manifestations are usually asymptomatic.

Keywords: Aortic aneurysm, autosomal dominant polycystic kidney, chronic renal insufficiency.

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary renal diseases.¹ This disease has been characterized primarily by the formation of bilateral multiple cysts in the kidneys and, frequently, in the liver and pancreas.² Although renal cysts are detectable in childhood, renal insufficiency usually begins between the third and fourth decade of life,² due to replacement of functioning renal parenchyma with multiple cysts. This is caused by gene PKD1 mutations, leading to dominant polycystic kidney disease type I (85% of cases), or gene PKD2 mutations, leading to dominant polycystic kidney disease type II (15% of cases),¹ both localized on chromosome 16 p33.3. Furthermore, the increased metalloproteinase production and secretion by kidney tubules could be involved with disease manifestation.³

Several extrarenal manifestations have been reported in the literature. From a vascular point of view, abdominal aortic,² peripheral,⁴ and visceral⁴ aneurysms, dissection of the thoracic aorta⁵ and carotid,⁶ and intracranial aneurysms^7,8 have been described. These alterations, if not diagnosed and repaired promptly, may lead to early death of these patients.

Case report

A 66-year-old male patient, married, referred to a nephrologist due to non-dialytic renal insufficiency resulting from dominant polycystic kidney disease, with controlled hypertension and use of nifedipine and furosemide. Laboratory tests were normal, except for a serum creatinine of 3.3mg/dL. The patient was referred to a vascular surgery service due to an asymptomatic abdominal aortic aneurysm diagnosed by routine ultrasonography. Clinically asymptomatic. He showed a good perfusion of the lower limb, and infrainguinal pulse was present and full. Noncontrast abdominal computed tomography revealed bilateral multiple cysts, in addition to hepatic cysts and an aneurysmal dilatation of the infrarenal abdominal aorta of 4.3 cm in greatest diameter (Figure 1), showing a growth of 0.6 cm in its greatest diameter when compared to the last tomography performed 6 months earlier. The patient underwent surgical management via transperitoneal access, with an aortobiiliac graft, infrarenal clamping and interposition of an 18 x 9 mm Dacron bifurcated graft. The presence of renal and hepatic cysts did not hinder surgery, and no postoperative complications occurred. Renal function alterations were not observed. The patient was discharged from the hospital on postoperative day 7 and is in outpatient follow-up.

Discussion

There is a significant prevalence of dominant polycystic kidney disease among hemodialysis patients, reaching, in some studies, 7.6% of the cases.¹ High morbidity and mortality of these patients is attributed to extrarenal manifestations of the disease.

Approximately 8% of patients with dominant polycystic kidney disease show asymptomatic intracranial aneurysms.⁸ The rupture rate is 1/2,000 person-years, a rate five times higher than in the general population,⁸ leading to early death in these patients.⁷

Abdominal aortic aneurysms may occur in patients with dominant polycystic kidney disease.² Evidence from the literature suggests an incidence of 0.7 to 9.7% in abdominal aortic aneurysms in patients with dominant polycystic kidney disease.² Despite their low incidence rate, abdominal aortic aneurysms, when ruptured, show a mortality rate between 30 and 55%, a value much higher than that observed in elective surgeries. Such data warrant complementary tests in these patients in order to catch asymptomatic aneurysms and repair them electively.² Great care should be given to chronic renal disease patients during the preoperative and intraoperative periods, such as use of noncontrast tomography, adequate hydration, shorter aortic clamping time, and infrarenal clamping if possible, since the presence of renal insufficiency is associated with a higher morbidity and mortality rate in patients undergoing surgical repair of aortic aneurysms. In addition to aneurysms, dissections of the thoracic aorta and the supra-aortic trunks are also described in the literature on patients with dominant polycystic kidney disease.

ADPKD types I and II are related to PKD1 and PKD2 genes, respectively, both located on chromosome 16. These genes encode proteins named polycystin-1 and polycystin-2, which are related to the structural integrity of blood vessels.⁸ Studies on aneurysms in patients with dominant polycystic kidney disease have shown protein expression on their wall. Additionally, these patients have demonstrated alterations in extracellular matrix components, such as fibronectin, collagen type IV, and proteoglycan.⁵ These alterations could weaken the vessel wall, causing aneurysms and dissections. Genetic changes on chromosome 16 were initially described in a kindred with dominant polycystic kidney disease and vascular dilatation.⁹

Vessel wall weakening, associated with arterial hypertension, has been related to an increased incidence of arterial dissections in these patients.^5,6 In particular, in abdominal aortic aneurysm cases in patients with dominant polycystic kidney disease, in addition to the defects in PKD1 and PKD2 genes, another hypothesis has been advanced in the pathogenesis of the disease: the increased metalloproteinase secretion by kidney tubules in these patients, especially metalloproteinase-2 and metalloproteinase-9. Takagi & Umemoto³ demonstrated high levels of metalloproteinase in the blood and the aortic aneurysm wall. Metalloproteinase-2 would contribute to elastin degradation in the aortic wall and its replacement with collagen, leading to conditions that weaken the aortic wall and may give rise to aneurysms.¹⁰ Metalloproteinase-9 has a chemotactic action on macrophages, neutrophils and other inflammatory cells, leading to a chronic inflammation of the vessel wall.¹⁰

Therefore, we can observe that vascular alterations in patients with dominant polycystic kidney disease are part of a complex genetic syndrome, which does not show only renal cysts. Among extrarenal manifestations, a significant rate of early mortality and morbidity in ADPKD patients is attributed to vascular manifestations, which are mostly asymptomatic, thereby warranting the use of equipped propedeutics in their investigation and early elective surgical repair.

References

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• 7. Schrier RW, Belz MM, Johnson AM, et al. Repeat imaging for intracranial aneurysms in patients with autosomal dominant polycystic kidney disease with initially negative studies: a prospective ten-year follow-up. J Am Soc Nephrol. 2004;15:1023-8.
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Publication Dates

• Publication in this collection
  02 Oct 2009
• Date of issue
  June 2009

History

• Received
  01 Sept 2008
• Accepted
  13 Jan 2009