ABSTRACT
Chronic kidney disease (CKD) causes cognitive impairment and contributes to the overall global burden of dementia. However, mechanisms through which the kidneys and brain communicate are not fully understood. We established a CKD mouse model through adenine-induced tubulointerstitial fibrosis. Novel object recognition tests indicated that CKD decreased recognition memory. Sarkosyl-insoluble-proteomic analyses of the CKD mouse hippocampus revealed an accumulation of insoluble MAPT (microtubule-associated protein tau) and RNA-binding proteins such as small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70). Additionally, there was an accumulation of Immunoglobulin G (IgG), indicating blood-brain barrier (BBB) breakdown. We identified that expressions of essential tight-junction protein claudin-5 and adherens-junction protein platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) were decreased in the brain endothelial cells of CKD mice. We determined urea as a major uremic solute that dose dependently decreased both claudin-5 and PECAM-1 expression in the mouse brain endothelial cell line bEnd.3 cells. Gelatin zymography indicated that the serum of CKD mice activated matrix metalloproteinase-2 (MMP2), while marimastat ameliorated the reduction of claudin-5 expression by urea in bEnd.3 cells. This study established a brain proteomic signature of CKD indicating BBB breakdown and insolubility of tau protein, which are pathologically linked to Alzheimer's disease. Urea-mediated activation of MMP2 was partly responsible for BBB breakdown in CKD.
Subject(s)
Blood-Brain Barrier , Renal Insufficiency, Chronic , Animals , Mice , Blood-Brain Barrier/metabolism , Claudin-5/metabolism , Endothelial Cells/metabolism , Matrix Metalloproteinase 2/metabolism , Platelet Endothelial Cell Adhesion Molecule-1 , Proteomics , Renal Insufficiency, Chronic/metabolism , tau Proteins/metabolismABSTRACT
The extent of rare side effects of mRNA vaccines for coronavirus disease 2019 (COVID-19) remains unclear. Several cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following COVID-19 vaccination have been reported. We herein report a 72-year-old man who presented with a fever after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. He was diagnosed with acute kidney injury due to myeloperoxidase-ANCA-associated vasculitis and was treated with intermittent hemodialysis, high-dose prednisolone, and intravenous rituximab. His general symptoms and renal impairment subsequently improved. When systemic symptoms are prolonged or renal abnormalities appear after COVID-19 vaccination, the possibility of AAV should be considered.
