Mechanisms of Cerebral Microvascular Disease in Chronic Kidney Disease

Numerous studies report linkage between chronic kidney disease (CKD) and cerebrovascular disease. This association has been particularly strong for cerebral small vessel disease. Significant findings have emerged from studies ranging from case reports, small case series, and larger cohort investigations. The latter show a relationship between declining renal function, microvascular disease, and cognitive impairment. One troubling aspect has been the relative paucity of mechanistic investigations addressing the CKD-cerebrovascular disease linkage. Nevertheless, mechanistic observations have begun to emerge, showing cerebral microhemorrhage development in animal models of CKD independent of hypertension, an important co-morbidity in clinical studies. Initial cell culture studies show endothelial monolayer disruption by CKD serum, consistent with blood-brain barrier injury. It is noteworthy that CKD serum is known to contain multiple plausible mediators of microvascular injury. Further studies are on the horizon to address the critical question of potential linkage of renal dysfunction with vascular cognitive impairment.