Adjunctive Human Urinary Kallidinogenase Enhances the Cognitive and Hemodynamic Outcomes of Anterior Circulation...

Chronic cerebral hypoperfusion due to anterior circulation stenosis contributes to cognitive decline. This study examined whether preoperative human urinary kallidinogenase (HUK) administration improves outcomes following percutaneous transluminal angioplasty with stenting (PTAS). In this prospective non-randomized controlled trial, 128 patients with severe anterior circulation stenosis were included in the HUK and control groups, respectively. The primary endpoint was change in Mini-Mental State Examination (MMSE) score at 90 days. Secondary outcomes included changes in Montreal Cognitive Assessment (MoCA) and National Institutes of Health Stroke Scale (NIHSS) scores, perfusion parameters, and inflammatory biomarkers. Propensity score adjustments addressed selection bias. Besides mechanical revascularization by PTAS, HUK pretreatment improved cognitive recovery (ΔMMSE, 5 vs. 2; adjusted p < 0.01) and domain-specific gains in memory, calculation/attention, language, and visuospatial function. HUK significantly promoted postoperative mean transit time (MTT) reduction (1.8 ± 1.3 vs. 0.9 ± 0.6, adjusted p < 0.01), indicating enhanced microcirculatory flow. HUK attenuated ΔIL-6 (18.6 ± 16.2 vs. 26 ± 18, adjusted p = 0.03) and amplified ΔIL-10 (2 ± 0.9 vs. 0.4 ± 0.2, adjusted p < 0.01). Baseline TNF-α predicted cognitive recovery (OR = 0.7, p = 0.03). Safety profiles were comparable (9.4% vs. 10.9% complications, p > 0.05), with no mortality. Collectively, adjunctive HUK administration before PTAS in patients with anterior circulation stenosis was associated with greater cognitive improvement and enhanced microvascular hemodynamics, potentially through anti-inflammatory and perfusion-modulating effects. Larger randomized controlled trials are warranted to validate these associations and elucidate the underlying mechanisms.Trial registration: Chinese Clinical Trial Registry. URL: https://www.chictr.org.cn/ ; unique identifier: ChiCTR2100053351.