In this national prospective cohort study of patients initiating dialysis for end-stage renal disease, cerebrovascular events including fatal and non-fatal clinical stroke and carotid endarterectomy occurred ten times more frequently than in the general population,8, 17
with an incidence rate of 4.9 per 100 person years. The majority of events were related to ischemic stroke, with cardioembolic stroke being the most common form of ischemic stroke among dialysis patients. To our knowledge, this is one of the first studies to classify ischemic stroke in dialysis patients into etiologic subtypes based on the TOAST criteria.12
This allows us to potentially alter our stroke prevention strategies from those used in the general population[ND2]. We found that dialysis patients with stroke present rather late after symptom onset, leaving little room for early interventions. Dialysis patients also have high fatality and low recovery rates. Dialysis patients and their families may need better education about stroke warning signs and symptoms and encouragement to bring these symptoms to their providers’ attention quickly.
We found that ischemic stroke was more common than hemorrhagic stroke in our national US dialysis cohort. This is consistent with a prior study relying on national administrative data.2
Few other studies have characterized stroke types except for a Japanese cohort of 151 patients, in whom hemorrhagic stroke was the most common type of stroke.18
Causes of hemorrhagic stroke may differ from ischemic stroke on long-term dialysis and thus acquired risk factors could account for this later hemorrhagic stroke risk. Reasons could include excess vascular calcification and stiffness,19, 20
leading to worsening hypertension. This, combined with the use of anticoagulation on dialysis, could increase hemorrhagic stroke.
For ischemic stroke, cardioembolism was the most common subtype, though all ischemic stroke subtypes were well represented. In addition to preventing vascular calcification and arterial stiffness, treatment of underlying cardiac disease at dialysis initiation may mitigate future stroke risk in this high-risk population. The use of aspirin in dialysis patients has been associated with a reduced risk of stroke, but the overall strength of this association was modest, as noted in the international Dialysis Outcomes and Practice Patterns Study (DOPPS).21
Baseline cardioembolism risk factors in our study, such as arrhythmias, left ventricular hypertrophy, valvular disease, and congestive heart failure, were not significantly different between individuals that experienced a cerebrovascular event versus those that did not in our cohort, suggesting these aspects may not be correctly identified in dialysis patients. Measurement of cardiac function by echocardiography has been suggested for all patients initiating dialysis22
because of its more accurate assessment than physical examination and chest radiography in identifying cardiac dysfunction and valvular disease. Furthermore, arrhythmias are common among dialysis patients and early recognition and treatment of these arrhythmias may also reduce the risk of stroke. The use of other prevention measures, such as statins, had not been associated with a decreased risk of stroke in prevalent diabetic hemodialysis patients in the 4D (Die Deutsche Diabetes Dialyse) study.23
Whether similar findings hold for incident dialysis patients is unclear.
The median time to presentation was over 8 hours, which is much longer than that observed in a systematic review of the literature on all strokes,24
signifying symptoms of stroke may be missed by providers and/or patients. This is especially problematic since patients on hemodialysis have regular access to the health-care system. With this delay in presentation, any benefit from earlier interventions in this population such as thrombolytic use25
may not be practiced, thus worsening mortality and morbidity after stroke. Improved education about symptoms of transient ischemic attack or stroke itself, such as numbness, weakness, confusion, or difficulty speaking should be given to dialysis patients and their families. One might suspect that stroke is more common during or immediately after a dialysis session due to changes in cerebral blood flow.6
In a study by Toyoda, 34% of ischemic brain infarcts occurred within 30 minutes of the dialysis procedure.18
Thirty percent of abstracted strokes in this study occurred either during the dialysis session or several hours later, though this timing was not statistically different from events that occurred on an intradialytic[ND3] day. A larger study may need to be undertaken to observe any temporal trends.26
Outcomes after stroke, especially hemorrhagic stroke, were poor with a high case-fatality and low “successful recovery” rate. Based on this study, for every 100 dialysis patients who have a stroke, thirty-five of them will die within thirty days, and only fifty-six of the one hundred patients will be able to go home or to an acute rehabilitation facility. While this low “successful recovery” rate is similar to that found in an earlier single-center cohort of prevalent hemodialysis patients followed in New York,27
it is inferior to the 10% adjusted stroke case-fatality rate seen in the Atherosclerosis Risk in Communities (ARIC) cohort28
and the 20% of patients requiring institutional care in the general population.28
This likely reflects the comorbid conditions that our patients on dialysis accumulated before they experienced a stroke. The overall length of hospital stay, surprisingly, was similar to that observed in the general population using the National Hospital Discharge Survey.29
This implies that practice patterns of post-stroke care, including evaluation, management, and disposition, may be similar across populations.
As a national prospective cohort study with characteristics similar to the 1997 US dialysis population, the results of this study may be generalizable to the population of patients initiating dialysis. The follow-up of up to 9.5 years in this study also allowed for evaluation of changing stroke etiologies over time on dialysis. Our ability to have such lengthy follow-up with well-described characteristics and events is a unique aspect of this study.
This study has some limitations which deserve mention. We had a relatively small number of cerebrovascular events, which limited our ability to evaluate specific risk factors for stroke subtypes. We also did not have medical records on all stroke events to classify stroke; however, the subset of the population with medical records of the stroke event did not differ from those with no medical record. In the cases where a chart was not available, the use of administrative data might not necessarily reflect an admission for an acute cerebrovascular event. In addition, CEA could potentially involve a referral bias and thus may not represent an acute event; however, the CEA events which we were able to abstract involved symptomatic disease or significant intraluminal stenosis suggesting these events were indicative of clinically meaningful cerebrovascular disease.
We conclude that cerebrovascular events are common in patients initiating dialysis. Dialysis-related risk factors for all types of cerebrovascular events may differ by the type of event and timing of event after dialysis initiation. This classification of cerebrovascular event types may help focus our efforts to better treat and prevent recurrence of stroke, thereby improving the prognosis of dialysis patients. Further studies to understand the pathophysiology, prevention, and treatment of cerebrovascular disease in ESRD need to focus on subclinical disease, including cognitive function,30
cerebral white matter changes,31
and subclinical strokes,3
as well as imaging techniques with magnetic resonance imaging to earlier identify cerebrovascular disease.