Autosomal Dominant Polycystic Kidney Disease in Aneurysmal Subarachnoid Hemorrhage
Published on: June 26, 2024
Case Details
A 49-year-old man was in his usual state of health when he experienced sudden onset worst headache of life followed by right arm and leg weakness. His wife called 911, and he was brought to the Emergency Room. Vital signs were notable for a blood pressure of 196/105. He was complaining of 10/10 headache and neck pain. He reported a history of headaches, but never this severe. On neurologic examination, he was awake, alert, and oriented to self, place, and date. His speech was slightly hypophonic but fluent. He followed commands briskly. Cranial nerves were intact. His motor exam was notable for 4/5 strength in his right upper extremity, but strength was otherwise full throughout. Sensation and coordination were intact. Past medical history was significant for autosomal dominant polycystic kidney disease (ADPKD) which was diagnosed in October of 2021 as well as hypertension. His mother also had ADPKD. His only home medication was losartan. Labs were notable for a creatinine of 1.4, which was at his baseline renal function. Non-contrast CT of the head showed diffuse subarachnoid hemorrhage without intraventricular hemorrhage. CT angiogram of the head and neck revealed a 2x2 millimeter superiorly oriented basilar tip aneurysm. He underwent right frontal external ventricular drain (EVD) placement and successful coil embolization of the basilar tip aneurysm.
Bedside renal point of care ultrasound (POCUS) was performed. This was done using the phased array probe on the abdominal setting but can also be performed with the curvilinear probe. The probe indicator was oriented toward the patient’s head. The probe was then placed in the right midaxillary line around the tenth intercostal space. The kidney was visualized through an acoustic window provided by the liver. On the left side, the probe was placed at a slightly higher intercostal space. The left kidney was identified through an acoustic window from the spleen. From these views, we were able to evaluate the renal parenchyma. Our patient’s renal POCUS (Figures 1-3) showed enlarged kidneys without hydronephrosis. His renal parenchyma was almost entirely replaced by numerous cysts of varying size and echogenicity. It was nearly impossible to discern normal renal structures. There were small hyperechoic areas within both kidneys likely reflecting calcification of the cyst walls.
He had an uncomplicated hospital course. His headache and right arm weakness resolved. The EVD was removed. He was ultimately discharged home with outpatient physical therapy services.
Discussion
Subarachnoid hemorrhage carries high rates of morbidity and mortality. Mortality rates within the first 30 days are variable but approach up to 30%.1 Several risk factors have been identified to cause physiologic alterations in flow that can ultimately lead to aneurysm formation. These include smoking, hypertension, age over 50 years, and excessive alcohol intake.2 Less common risk factors include congenital conditions such as Marfan’s syndrome, Ehlers-Danlos Syndrome, and ADPKD.3
ADPKD occurs in approximately 1 in 1000 live births and is the most common genetic cause of renal failure worldwide.4 It is characterized by renal cysts that lead to gradual enlargement and impairment of the kidneys.5 Due to this slowly progressive nature, the majority of patients do not become symptomatic until the ages of 30-50 years.6 Mutations in three genes have been identified that contribute to the onset of ADPKD: PKD1 mutations account for 85% of cases, 15% are due to PKD2, and 1% have GANAB mutations. PKD1 associated ADPKD is considered more severe and is associated with an earlier age of onset and formation of larger and more numerous cysts than in PKD2.7 While ADPKD is considered a genetic condition, 15% of cases are related to non-inherited mutations.5
The most common symptom of ADPKD is hypertension. While classically thought of as causing renal disease, extrarenal manifestations of ADPKD include hepatic and pancreatic cysts, abdominal hernias, colonic diverticula, cardiac valvular disease, and vascular malformations such as coronary and cerebral artery aneurysms.5 Intracranial aneurysms occur in ADPKD patients at a rate of 8-12%, which is four times higher than the general population (2-3%).7 The increased frequency of aneurysm formation in ADPKD is thought to be due to underlying endothelial dysfunction. These patients have increased inflammatory markers and reduced availability of nitric oxide, resulting in increased susceptibility to the formation of aneurysms in the setting of uncontrolled hypertension or smoking.8 Aneurysmal rupture leading to subarachnoid hemorrhage is one of the most serious complications of ADPKD. Aneurysmal rupture rate for patients with ADPKD is five times higher than the general population.9 It was also found to occur in younger patients with smaller aneurysms.5
Given the significant morbidity and mortality associated with aneurysmal subarachnoid hemorrhage, proper identification of patients at risk for intracranial aneurysm formation in ADPKD is critical. Screening for intracranial aneurysms is indicated for patients with ADPKD who have a family or personal history of intracranial aneurysm or subarachnoid hemorrhage, a high-risk occupation where rupture would place the individual or others at high risk, those who require surgery that may lead to hemodynamic instability or hypertension, or those with significant additional risk factors for aneurysm formation.
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References
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- Alg VS, Sofat R, Houlden H, et al. Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals. Neurology. 2013;80(23):2154-2165. https://doi.org/10.1212/WNL.0b013e318295d751
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- Alam A, Cornec-Legall E, Perrone RD. What is autosomal dominant polycystic kidney disease? JAMA. 2023;329(13):1128. https://doi.org/10.1001/jama.2023.2126
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- Harris PC, Torres VE. Polycystic kidney disease, autosomal dominant. 2002 Jan 10. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. Gene Reviews [Internet]. Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1246
- You I, Chapman A. Intracranial aneurysms in ADPKD. Clin J Am Soc Nephrol. 2019;14(8):1119-1121. https://doi.org/10.2215/CJN.07570719
- Perrone RD, Malek AM, Watnick T. Vascular complications in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2015;11(10):589-598. https://doi.org/10.1038/nrneph.2015.128