Lukas Mayer, MD
The increased cardiovascular risk of patients with chronic kidney disease (CKD) has been acknowledged for quite some time. Consequently, incidence of cerebrovascular events in CKD cohorts has routinely been assessed. Interestingly however, studies focusing on the incidence of CKD in ischemic stroke cohorts or the possible relationship between CKD and ischemic stroke etiology are scarce.
Through their analysis of patients with cerebral ischemia within the population-based OXVASC study, Kelly and co-authors present a detailed look into stroke etiology in subjects with CKD. The ongoing OXVASC study currently envelopes more than 90,000 individuals, of which 3,178 suffered ischemic stroke/TIA (N=2.696) or intracerebral hemorrhage (N=209). Kelly et al. used the TOAST classification, which denotes five subtypes of cerebral ischemia (cardioembolism, large artery disease, small vessel disease, unknown, other etiology), and tried to establish a possible linkage of specific stroke subtypes and chronic kidney disease, which the study team defined as eGFR ≤60mL/min/1.73m2 being evident 3 months or longer.
Focusing on subjects with cerebral ischemia, a total of 1197 (~40%) had chronically reduced kidney function. During group comparison, TOAST subtypes differed significantly, as “cardioembolism” and “unknown” were more likely in patients with CKD and “small vessel disease” and “other” in those with normal kidney function. But, after adjusting for age, sex and hypertension in uni- and multivariate regression, the risk association between evidence of CKD and TOAST subtypes proved to be non-significant. In detailed analyses, younger subjects (i.e., <65 y.o.) with CKD had a higher risk of ischemia being caused by cardioembolic events.
Conclusively, the authors state that no clear independent positive association between CKD and specific TOAST subcategories in ischemic stroke can be defined. Therefore, Kelly et al. suggest that renal-specific risk factors are unlikely to play a role in etiologic manifestation of cerebral ischemia.
Though excellently executed, some limitations have to be mentioned. On average, patients’ age was higher than the validated threshold for accurate interpretation of eGFR measures. It would have been rewarding to add albuminuria to fully document KADIGO categories of renal dysfunction to accurately depict CKD, especially in older individuals. Further, even though TOAST is the most widely used method of etiologic ischemic stroke categorization, it would have been interesting to involve a more detailed system of classification (i.e., the Causative Classification of Stroke System). Lastly, it would have been intriguing to depict how many of the cardioembolic strokes in younger individuals were attributed to atrial fibrillation, as an association between CKD and atrial fibrillation has been postulated.
In summary, this study emphasizes an often under-recognized, highly prevalent and important risk factor in cerebrovascular disease. Further analysis of the link between CKD and ischemic stroke is justified because CKD is very common not only in patients with cerebrovascular ischemia, but also because of the limitations it imposes on secondary prevention.
