Stroke in the Presence of Kidney Disease
Stroke is a life-threatening medical condition that occurs when blood supply to the part of the brain is cut off. It is one of the leading causes of death and disability around the world. Most strokes are caused by blockage of arteries to the brain while others are caused by bleeding brain tissue when a blood vessel bursts. The prevalence of stroke has numerous risk factors including hypertension, cardioembolism, leukoaraiosis, and atherosclerosis. Stroke can be divided into three subtypes:
- Ischemic – this is the most common type of stroke accounting for almost 80 percent of all strokes. It’s caused by a blockage within an artery leading to the brain.
- Hemorrhagic – this type of stroke is caused by a sudden rupture of an artery within the brain. Blood flows to the brain and compresses the brain structures.
- Transient Ischemic – this stroke only lasts for a few minutes and happens when the blood supply to the brain is briefly blocked. Symptoms do not last long and may include weakness or numbness on one side of the body.
Stroke and Kidney Disease Connections
Kidneys are vital organs to our body. They remove waste and extra fluid inside us. They are also in charge of removing acids that are produced by our cells so that we can maintain a healthy balance of water, salts, and minerals. Any changes from this may result in a direct or indirect impact on the brain.
Both acute kidney injury and chronic kidney disease (CKD) are linked with an increased risk of cerebrovascular events and stroke. However, the mechanism between impaired renal function and stroke remains unexplored which has allowed for many researchers to study for therapeutic interventions.
One of the primary causes for cerbrorenal interactions is the vasoregulatory, anatomic, and hemodynamic similarities of the vascular beds. Cerebral perforating and glomerular afferent arterioles of the juxtamedullary nephron in the brain and kidney are both short and small that arise from very high pressure, large arteries, responsible for maintaining the perfusion pressure and blood flow. So when they are exposed to high pressure and injury, they pose a substantial risk for cerebrovascular diseases. In fact, increased proteinuria and declining glomerular filtration rate actually affect the brain arteries.
This observational study summarizes the intricate mechanisms found in cerberorenal interactions. The researchers emphasized the mechanistic effects of different factors involved in kidney diseases such as atherosclerosis, cerebral small vessel disease (SVD), platelet dysfunction, hyperphosphatemia, hyperglycemia, and hyperlipidemia.
Mechanisms of Cerebrorenal Interactions
Kidney disease leads to a decrease in GFR affecting interstitial tissues, glomerular tubules, and blood vessels. The prolonged injury also leads to inflammation and production of profibrotic cytokines which results in the development of various risk factors that exacerbate cerebrovascular diseases.
Anemia caused by iron deficiency is an uncommon cause of ischemic stroke. However, many studies report that among patients who are anemic, 18,4% experienced a minor stroke, 26.3% experienced a moderate stroke, while 55.3% experienced a severe ischemic stroke, showing an association between anemia and stroke severity.
Arteriosclerosis and Endothelial Dysfunction
Arteriosclerosis occurs when blood vessels that bring oxygen and nutrients to the heart become stiff and thick which restricts blood flow to organs and tissues. In most renal dysfunction cases, arteriosclerosis is found to be the leading cause of stroke.
Atrial Fibrillation (AF)
Atrial fibrillation is associated with thromboembolic stroke incidence. Studies reported prevalence in the CKD population. Declining eGFR, proteinuria, and AF are the dominant factors that contribute to thromboembolic stroke. Men are more likely to have AF compared to women.
Platelet dysfunction in renal diseases is often an outcome of inherent platelet anomalies including abnormal interaction with the vascular wall. Platelet aggregation during normal hemostasis is initiated upon vascular injury and is maintained by the balance between anticoagulants and fibrinolytic agents.
These toxins are internally produced molecules devoid of interference by foreign toxins, intestinal absorption, and metabolically modified products. Gut flora is also responsible for the toxic constitution and functioning of healthy gut microflora.
Protein carbamylation is a result of renal impairment like CKD. It is also a threat to cerebrovascular diseases such as stroke. Studies have found the prevalence of carbamylated protein homocitrulline in disorders such as stroke, myocardial infarction, and peripheral artery disease.
The by-product of methionine metabolism is found in the body due to deficiency of its recycling mediators or abnormal metabolism. It can also be caused by renal disease which can strongly correlate with cerebrovascular events.
Another cerebrovascular risk factor that is caused by renal failure. Phosphate excretion also plays a crucial role in the kidney in maintaining phosphate balance. In most kidney injury or renal dysfunction, the loss of phosphorous homeostasis often leads to a decrease in excretion of phosphorous and thus causes hyperphosphatemia.
Our kidneys are important in maintaining the balance of acids and electrolytes. Without them, our cells wouldn’t function well. Metabolic acidosis in renal failure has a severe effect on the cerebroneural metabolism which threatens normal cerebral function.
Cerebral SVD is the process of distributing venules, arterioles, and capillaries of the brain. SVD with renal dysfunction is documented in various studies. However, the mechanism for its development is not yet clear.
Cerebral Microbleeds (CMB)
CMB is a manifestation of cerebral SVD which can represent its association with cerebrovascular events such as stroke. CMB is often a distinct hypointense lesion in the brain which appears on T2*-weighted gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI) ranging from < 5mm-10mm in size.
White matter hyperintensities (WMH)
WMH is also known as leukoaraiosis and is often associated with risk factors such as cardiac disease, hypertension, and renal disease resulting in vascular damage. WMH in ischemic stroke results in poor functional outcomes and cognitive impairment. A prospective cohort study proved the relationship between chronic kidney disease and WMH through various mechanisms.
Cerebro-renal vasoregulation exceeds common vascular risk factors. It also includes diseases such as hypertension, anemia, arteriosclerosis which leads to medial and endothelial wall dysfunction and increased risk for microhemorrhages and lacunar infarcts.