Kidney Health: Stroke Risk And Prevention

Stroke is a leading cause of death and disability worldwide. Renal failure is a potent risk factor for stroke, with the risk of stroke being 5–30 times higher in patients with chronic kidney disease (CKD), especially those on dialysis. CKD is often diagnosed by measuring creatinine clearance, proteinuria, cystatin C, albuminuria, estimated glomerular filtration rate (eGFR), urinalysis to evaluate for leukocytes and red blood cells, serum electrolytes, serum calcium, and parathyroid hormone levels. CKD may be a frequently encountered problem in post-ischemic stroke patients. CKD increases vascular dysfunction, vascular calcification, and arterial stiffness, which increases the risk of stroke as well as exacerbates the pathogenesis of stroke. CKD is associated with a greater neurological deficit following ischemic stroke, a poor functional outcome, and greater mortality.

The risk of stroke is 5–30 times higher in patients with chronic kidney disease, especially on dialysis

Chronic kidney disease (CKD) is an independent risk factor for stroke, including both hemorrhagic and ischemic subtypes. Patients with end-stage kidney disease (ESKD) receiving renal replacement therapy are at four-fold to ten-fold higher risk of stroke relative to the general population, and stroke risk increases by a factor of seven-fold during the initial year on dialysis. Patients with CKD and ESKD also have significantly poorer functional outcomes and greater mortality after suffering a stroke.

The risk for stroke was found to be five times higher in CKD patients on dialysis in comparison to the general population. In comparison to the general population, not only the stroke incidence, but also the death rate due to stroke were higher in the CKD and dialysis population.

CKD increases the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds, defined as small chronic brain hemorrhages that can act as a nidus for future hemorrhagic events. Among patients with ICH, an eGFR <45 mL/min/1.73 m2 is associated with a three-fold increase in the volume of the hematoma and a four-fold higher risk of death, compared to patients without renal impairment.

Compared to the general population, atrial fibrillation (AF) is more than twice as prevalent in patients with CKD and confers a greater risk for thromboembolism. The Chronic Renal Insufficiency Cohort reported a prevalence of AF in patients with CKD 2–3 times higher than in the general population. A report from 132,372 patients with nonvalvular AF in the Danish national registry found that patients with predialysis CKD or ESKD had increased risk of stroke and increased risk of intracranial bleeding relative to those with normal kidney function.

CKD increases the risk of large vessel stroke via its effects on carotid artery stenosis, plaque size, and carotid intima-media thickness. In a series of prospective carotid ultrasound and CT imaging studies of patients after a stroke, those with CKD had significantly higher internal carotid artery stenosis and plaque size, including after adjustment for conventional CVD risk factors. CKD was independently associated with carotid atherosclerosis in patients with hypertension.

The effects of reduced eGFR and increased albuminuria on small vessel ischemic stroke have been intensively studied. Small vessel disease causes 25% of ischemic strokes. Reduced eGFR and albuminuria are associated with higher prevalence of small vessel disease. The Northern Manhattan Stroke Study showed an eGFR of 15–60 mL/min/1.73 m2 was associated with a higher volume of white matter hyperintensities after adjusting for conventional CVD risk factors. The Rotterdam Scan Study, which focused on patients 60 years and older, found a similar higher prevalence of white matter lesions after multivariate adjustment (OR 1.11, 95% CI 0.81–1.51), as well as less deep white matter volume. More recently, a subgroup analysis from the Systolic Blood Pressure Intervention Trial identified increased white matter lesion burden in patients with reduced eGFR (<60 mL/min/1.73 m2) and high urine albumin-to-creatinine ratio.

CKD is often diagnosed by measuring creatinine clearance, proteinuria, cystatin C, albuminuria, estimated glomerular filtration rate, urinalysis, serum electrolytes, serum calcium, and parathyroid hormone levels

Chronic kidney disease (CKD) is a major public health concern, affecting around 15% of the US adult population. CKD is often diagnosed by measuring:

• Creatinine clearance
• Proteinuria
• Cystatin C
• Albuminuria
• Estimated glomerular filtration rate (eGFR)
• Urinalysis
• Serum electrolytes
• Serum calcium
• Parathyroid hormone levels

CKD is associated with a higher risk of stroke, with the risk increasing as kidney function declines. CKD can be detected for the first time during stroke evaluation, and the risk of stroke is higher in patients on dialysis. CKD is often accompanied by other risk factors for stroke, such as hypertension, diabetes, atherosclerosis, anemia, hyperlipidemia, and hyperhomocystinemia.

The estimated glomerular filtration rate (eGFR) is an important measure of kidney function, calculated using serum creatinine levels, age, and sex. A "normal" eGFR varies according to age and is used to determine the stage of CKD. CKD is defined as abnormal kidney structure or function lasting more than three months, with an eGFR of less than 60 ml/min/1.73 m2 indicating reduced kidney function.

Cystatin C is a protein produced by cells in the body and removed through the kidneys. It can be measured instead of, or in addition to, serum creatinine to assess kidney function, particularly in patients with elevated serum creatinine levels but no known CKD, risk factors, or albuminuria.

Urine albumin-creatinine ratio (uACR) and urine protein-creatinine ratio (uPCR) are also used to assess kidney function, with higher levels indicating worse kidney function.

In addition to these measures, other tests may be used to assess CKD complications, such as anemia, mineral and bone disorders, cardiovascular disease, and diabetes.

CKD may be a frequently encountered problem in post-ischemic stroke patients

CKD is a frequently encountered problem in post-ischemic stroke patients. In a large-scale multicenter hospital-based study, approximately 35% of first-ever stroke patients exhibited symptoms of CKD. In a nationwide study of Medicare-aged acute ischemic stroke patients, low eGFR and dialysis status on admission were independent and strong predictors of poor outcomes. CKD is often diagnosed by measuring creatinine clearance, proteinuria, cystatin C, albuminuria, estimated glomerular filtration rate (eGFR), urinalysis to evaluate for leukocytes and red blood cells, serum electrolytes, serum calcium, and parathyroid hormone levels. Among these parameters, eGFR is the most commonly used by clinicians to identify the stage of CKD.

CKD is an independent risk factor for both ischemic and hemorrhagic stroke

The heightened risk of stroke in CKD represents the interplay of the vascular co-morbidities that occur with renal impairment and factors specific to renal failure such as malnutrition-inflammation-atherosclerosis complex, the effect of uremic toxins, dialysis techniques, vascular access, and the use of anticoagulants to maintain flow in the extracorporeal circuit. Old age, hypertension, diabetes, and previous cerebrovascular disease are all risk factors for stroke with the period of dialysis initiation constituting the highest risk period for developing new stroke. Patients with CKD-stage 3–5 have worse survival and diminished functional outcomes following stroke.

The risk factors for stroke are: hypertension in 88.88% (uncontrolled hypertension 48.14%), anemia in 81.48%, diabetes in 48.14%, smoking in 33.33%, and hyperlipidemia in 14.81% of the patients.

CKD patients are at heightened risk for all subtypes of stroke

CKD patients are at a heightened risk for all subtypes of stroke. The risk of stroke is 5–30 times higher in patients with CKD, especially on dialysis. The heightened risk of stroke in CKD represents the interplay of the vascular co-morbidities that occur with renal impairment and factors specific to renal failure such as malnutrition-inflammation-atherosclerosis complex, the effect of uremic toxins, dialysis techniques, vascular access, and the use of anticoagulants to maintain flow in the extracorporeal circuit.

The risk factors for stroke in CKD patients include non-modifiable risk factors such as older age, diabetes, male gender, non-Caucasian/Asian ethnicity, and a positive family history. Hypertension continues to be the major modifiable risk factor for both ischemic and hemorrhagic stroke with risk increasing with worsening systolic and diastolic blood pressure control. Atherosclerotic risk factors such as smoking, hyperlipidemia, and atrial fibrillation (AF) increase the risk of ischemic stroke. The prevalence of AF in CKD patients is more than twice that in the general population.

CKD patients with ESRD on dialysis have an 8–10 times greater incidence of stroke compared to the general population. The risk of hemorrhagic stroke has been reported to be higher than ischemic stroke in hemodialysis (HD) patients when compared to peritoneal dialysis (PD) patients, though this has not been consistently the case, especially in recent studies.

The outcome of stroke in CKD patients is also poor. CKD is an independent risk factor for both ischemic and hemorrhagic stroke. Renal impairment is associated with a greater neurological deficit following ischemic stroke, a poor functional outcome, and greater mortality.

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