Abstract TP292: Chronic Kidney Disease Exacerbates Post-Stroke Cell Death and Inflammatory Mechanisms

Abstract

Chronic kidney disease (CKD) is an important independent risk factor for stroke. To understand the mechanisms of CKD that exacerbates stroke pathogenesis, we developed a rodent CKD model by feeding adult C57BL/6 mice with adenine. There was a gradual progression of CKD from mild to severe stages between days 7 and 28 identified by a combination of hematological (creatinine, blood urea nitrogen, and total protein) and imaging (MRI, μCT, dual-energy X-ray absorptiometry, and ultrasound) markers. The CKD cohort showed significant vascular fibrosis, collagen deposition, microvascular rarefaction, and tubulointerstitial abnormalities in the kidneys compared to the control. Induction of transient focal ischemia (by MCA occlusion) on day 28 of adenine treatment led to bigger infarcts (estimated by MRI on day 1 of reperfusion) and worsened motor function (assessed by rotarod test and beam walk test on days 1, 3, 7 and 14 of reperfusion) compared with non-CKD control cohort. The CKD group also showed twice higher mortality by day 14 of reperfusion after transient MCAO compared to control. Proteomic profiling showed that pro cell death and inflammatory mechanisms were directly induced in the brain by CKD pathogenesis. Overall, these studies conclude that CKD-induced cell death and inflammatory mechanisms in the brain contribute to severe and disabling stroke.