Where is the protocol located so all stroke hospitals will find and implement it? Oh, you INCOMPENTLY DIDN'T DO THAT? You're fired!
Role of human urinary kallikrein in reducing progressive ischemic stroke among acute ischemic stroke patients with concurrent hypertension and diabetes: a hospital-based retrospective cohort study
Zeyang Zheng†
Shanshan Yang
Zhongling Zhang- Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
Background: Progressive ischemic stroke (PIS) poses significant challenges in the management of acute ischemic stroke (AIS), with higher morbidity and mortality rates, especially among patients with vascular risk factors such as hypertension and diabetes. This study evaluates the efficacy of human urinary kallidinogenase (HUK) in reducing the incidence of PIS in patients with AIS, with a particular focus on subgroups based on vascular pathology and thrombolytic treatment.
Methods: This retrospective cohort study included 916 patients with AIS treated at a single tertiary care center between January 2022 and September 2023. The patients were divided into two groups based on whether they received HUK treatment in addition to standard care or standard care alone. The primary outcome was the incidence of PIS. Independent sample t-tests or chi-squared tests were used for univariate analysis between groups to identify potential predictors associated with the occurrence of PIS, with factors achieving a p-value < 0.1 considered for multivariate binary logistic regression analysis. Multivariate analysis adjusted for potential confounders to determine independent predictors significantly associated with PIS. The significance threshold was set at p < 0.05. In addition, subgroup analyses were conducted based on stroke subtype (TOAST classification), thrombolysis treatment, and infarction location.
Results: HUK treatment significantly reduced the incidence of PIS (p < 0.001), with the most notable effects observed in patients with large-artery atherosclerosis and small-artery occlusion, those not undergoing intravenous thrombolysis, and those with anterior circulation infarctions. Conversely, no significant reduction was noted in patients with cardioembolic stroke, other etiologies of infarction, intravenous thrombolysis, posterior circulation infarctions, or both anterior and posterior circulation infarctions. Factors such as low body mass index (BMI) and high activated partial thromboplastin time are associated with an increased risk of PIS.
Conclusion: HUK treatment appears to be an effective strategy for reducing the risk of PIS in patients with AIS, particularly in those at higher risk owing to specific vascular pathologies. These findings support the use of HUK in clinical practice to improve the outcomes of patients with stroke. Future prospective, multicenter, randomized controlled trials are warranted to validate these findings and further elucidate the underlying mechanisms.
1 Introduction
Stroke remains the second leading cause of death worldwide and the third most common cause of disability and mortality. Ischemic strokes, representing 62.4% of all new stroke cases, disproportionately affect populations in low to upper-middle-income countries, accounting for over 80% of stroke-related disability-adjusted life years (DALYs) (1). Notably, approximately 25 to 33% of stroke survivors develop PIS within days following the initial event, presenting with worsening neurological deficits and generally poorer prognostic outcomes (2).
HUK, a serine protease derived from urine, has garnered attention for its therapeutic potential in AIS, primarily through enhancing collateral circulation, stimulating angiogenesis, and improving cerebral perfusion (3–5). A longitudinal study involving 300 patients demonstrated that those receiving HUK exhibited notably lower scores on the modified Rankin Scale (mRS) at a 12-month follow-up compared to their counterparts in the control group (6). Moreover, a meta-analysis incorporating data from 24 studies quantified the neurologic improvement attributable to HUK, indicating a 0.56-fold increase in recovery rates (7). Focusing on patients with large artery atherosclerosis, another retrospective analysis revealed that HUK treatment was associated with significantly reduced National Institutes of Health Stroke Scale (NIHSS) scores (8).
Hypertension and diabetes are prevalent risk factors in the AIS patient demographic, with the National Inpatient Sample highlighting that 79% of these patients suffer from hypertension, and 34% are diabetic (9–11). Endothelial dysfunction, insulin resistance, and impaired vascular reactivity caused by hypertension and diabetes may increase the adverse risks in AIS patients. Previous studies have demonstrated that blood pressure levels in AIS patients are significantly associated with their neurological outcomes. Maintaining appropriate blood pressure levels can significantly improve the prognosis of AIS patients (12, 13). Given the high prevalence of these comorbidities and their significant impact on stroke outcomes, investigating the therapeutic potential in this high-risk subgroup is of great clinical significance. Despite these statistics, research into HUK’s effectiveness specifically for patients with AIS concurrently diagnosed with these conditions remains sparse. One study reported that patients with AIS with stage 3 hypertension undergoing HUK treatment showed substantial improvements in mRS scores and recovery rates 3 months post-treatment (14). Another study contrasting patients with AIS with abnormal glucose metabolism observed a significant reduction in NIHSS scores following HUK treatment, although mRS scores did not differ significantly between the treated and control groups (15).
Thus, the present study aimed to investigate the effects of HUK on the incidence of PIS post-admission in patients with AIS with both hypertension and with diabetes, with a subgroup analysis by site of lesions, TOAST subtypes, and the use of intravenous thrombolysis.
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