CLDN5 and chronic kidney disease: We further investigated the role of MMP2, which was found to be increased in the detergent-insoluble fraction of CKD brain (Figure 2B), in the loss of claudin-5 and CD31, given that MMP2 is the major pathophysiological regulator of BBB integrity by modulating claudin-5 expression and distribution in endothelial cells [36, 37].