Disentangling the multiple links between renal dysfunction and cerebrovascular disease

Abstract

Chronic kidney disease (CKD) has a rapidly rising global prevalence, affecting as many as one-third of the population over the age of 75 years. CKD is a well-known risk factor for cardiovascular disease and, in particular, there is a strong association with stroke. Cohort studies and trials indicate that reduced glomerular filtration rate increases the risk of stroke by about 40% and that proteinuria increases the risk by about 70%. In addition, CKD is also strongly associated with subclinical cerebrovascular abnormalities, vascular cognitive impairment and dementia. The mechanisms responsible for these associations are currently unclear. CKD is associated with traditional risk factors such as hypertension, diabetes mellitus and atrial fibrillation, but non-traditional risk factors such as uraemia, oxidative stress, mineral and bone abnormalities, and dialysis-related factors, such as changes in cerebral blood flow or cardiac structure, are also postulated to play a role. Kidney disease can also impact and complicate the treatments used in acute stroke and in secondary prevention. In this review, we will outline our current understanding of the epidemiology and pathophysiology of cerebrovascular disease in CKD.

Keywords: chronic kidney disease; dementia; dialysis; hypertension; stroke.

Figure 1

Mechanisms of susceptibility and injury in the shared pathway of renal and cerebrovascular diseases. FGF-23, fibroblast growth factor-23; GFR, glomerular filtration rate; LVH, left ventricular hypertrophy.

Figure 2

The strain vessel hypothesis: juxtamedullary afferent arterioles and cerebral perforating arteries are both exposed to high pressure and have to maintain large pressure gradients, rendering them susceptible to hypertensive injury.