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Chronic kidney disease measures and the risk of abdominal aortic aneurysm.

ABSTRACT: BACKGROUND AND AIMS:Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated. METHODS:In 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53-75 years during 1996-1998), we evaluated the associations of two key CKD measures - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4258 participants during 2011-2013. RESULTS:During a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58-12.49) for eGFR <30, 3.29 (1.89-5.72) for 30-44, 2.03 (1.29-3.19) for 45-59, and 1.62 (1.11-2.35) for 60-74 compared to eGFR ?90?mL/min/1.73?m2 and was 2.49 (1.28-4.87) for ACR ?300, 1.99 (1.40-2.83) for 30-299, and 1.46 (1.08-1.97) for 10-29 compared to ACR <10?mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed. CONCLUSIONS:Reduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA.

SUBMITTER: Matsushita K

PROVIDER: S-EPMC6295219 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Chronic kidney disease measures and the risk of abdominal aortic aneurysm.

Matsushita Kunihiro K Kwak Lucia L Ballew Shoshana H SH Grams Morgan E ME Selvin Elizabeth E Folsom Aaron R AR Coresh Josef J Tang Weihong W

Atherosclerosis 20180901

<h4>Background and aims</h4>Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated.<h4>Methods</h4>In 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53-75 years during 1996-1998), we evaluated the associations of two key CKD measures - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with in ...[more]

PMID: 30290962

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Project description:The purpose of this study was to establish a reliable, chronic model of abdominal aortic aneurysm (AAA).Wild-type 8-week-old C56BL/6 male mice (n = 120) were equally divided into three groups: (1) BAPN group: 0.2% 3-aminopropionitrile fumarate salt (BAPN) drinking water was provided to mice 2 days before surgery until the end of study. Sham aneurysm induction surgery was performed using 5 ?L of heat deactivated elastase. (2) Elastase group: mice were given regular drinking water without BAPN. During aneurysm induction surgery, 5 ?L of the active form of elastase (10.3 mg protein/mL, 5.9 U/mg protein) was applied on top of the infrarenal abdominal aorta adventitia for 5 minutes. (3) BAPN+elastase group: mice were given BAPN drinking water and the active form of elastase application, as above. On postoperative days 7, 14, 21, 28, and 100, aortic samples were collected for histology, cytokine array, and gelatin zymography after aortic diameter measurement.Compared with the elastase group, the BAPN+elastase group had a higher AAA formation rate (93% vs 65%; P < .01) with more advanced AAAs (25 of 42 vs 1 of 40 for stage II and III; P < .001). Aneurysms from the BAPN+elastase group demonstrated persistent long-term growth (221.5% ± 36.6%, 285.8% ± 78.6%, and 801% ± 160% on days 21, 28, and 100, respectively; P < .001), with considerable thrombus formation (54%) and rupture (31%) at the advanced stages of AAA development. Cytokine levels (pro-matrix metalloproteinase 9, interleukin-1?, interleukin-6, chemokine [C-C motif] ligand 5, triggering receptor expressed on myeloid cells 1, monocyte chemotactic protein 1, and tissue inhibitor of metalloproteinase 1) in the BAPN+elastase group were higher than in the elastase group on day 7. After day 7, cytokine levels returned to baseline, with the exception of elevated matrix metalloproteinase 2 activity. By histology, CD3-positive T cells in the BAPN+elastase group were elevated on days 28 and 100.A combination of oral BAPN administration and periaortic elastase application induced a chronic, advanced-stage AAA with characteristics of persistent aneurysm growth, thrombus formation, and spontaneous rupture. Future studies should use this model, especially for examining tissue remodeling during the late stages of aneurysm development.

Dataset Information

Chronic kidney disease measures and the risk of abdominal aortic aneurysm.

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Chronic kidney disease measures and the risk of abdominal aortic aneurysm.

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