A pooled analysis of patient data from the MICON international collaboration revealed that among patients with ischemic stroke (IS) or transient ischemic attack, impaired kidney function was associated with a higher risk of current stroke and higher microbleeds burden, relative to those with normal kidney function. Study authors concluded that impaired kidney function may identified high-risk patients for recurrent stroke, as well as optimizing treatment decisions to prevent recurrent vascular events.1
The analysis included 11,175 patients (mean age, 70.7 [±12.6]) with IS, of which 2815 (25.2%) had impaired kidney function, defined as estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. Through reocmmendations from the European Renal Association and the European Federation of Clinical Chemistry and Laboratory Medicine, the study authors chose to use the original 2009 CKD-EPI equation for estimate GFR, omitting the ethnicity coefficient.
Led by Jeremy Molad, MD, deputy director of the Neurology Division at Tel Aviv Medical Center, those with eGFR of less than 60 were older (mean age 77.3 [±9.8] vs 68.4 [±12.8]), had higher proportion of females (51.6% vs 39.1%) and had higher rates of all comorbidities. Over a median follow-up of 1 year, there were 802 primary outcome events, with higher rates of the composite outcome in the eGFR <60 group. Investigators recorded event rates of 58 per 1000 patient follow-up for this group vs 40 for those with normal eGFR (log rank test P <.001).
Between the two groups, the adjusted hazard ratio (aHR) for such events was 1.33 (95% CI, 1.14-1.54; P <.001) in favor of the eGFR <60 group. This association remained significant in the competing risks regression analysis, which accounted for the high rate of death in the eGFR <60 group (135 per 1000 person years; aHR, 1.32; 95% CI, 1.14-1.51).
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In the study, reduced renal function (eGFR <60) was independently associated with a higher risk of recurrent ischemic stroke (aHR, 1.33; 95% CI, 1.12–1.58) but not with symptomatic intracranial hemorrhage (aHR, 1.07; 95% CI, 0.70–1.60). Importantly, the presence of cerebral microbleeds, use of anticoagulation, or their combination did not modify the relationship between renal impairment and either recurrent ischemic stroke or symptomatic hemorrhage (all p interaction ≥0.71).
“Our study confirms that decreased eGFR provides predictive value for overt IS recurrence in patients with renal impairment receiving antithrombotic agents for secondary stroke prevention and that microbleeds do not alter the net harm of antithrombotic therapy,” Molad et al commented.
The lack of link between aticoagulant use, microbleed presence and the risk of recurrent IS or intracerebral hemorrhage has implications for clinical practice, “as many clinicians have expressed safety concerns regarding anticoagulant treatment in this high-risk population, supported by the superior safety and efficacy profile of Direct oral anti-coagulants (DOACs) compared with vitamin-K antagonists among CKD patients,” the study authors noted. “Nevertheless, we must interpret these findings with caution, given the observational nature of the current study, potential indication bias and the potential for incomplete adjustment for confounding variables.”
Beyond stroke recurrence, eGFR <60 was also linked to microbleed presence (aOR 1.14; 95% CI, 1.03–1.26) and severity (aOR 1.17 per category; 95% CI, 1.06–1.29). A negative binomial regression confirmed an association with microbleed count (IRR 1.20; 95% CI, 1.05–1.37). When stratified by distribution, lower eGFR was most strongly associated with lobar (–2.10; 95% CI, –3.39 to –0.81) and mixed microbleeds (–2.42; 95% CI, –3.70 to –1.15), with smaller effects observed for deep microbleeds.