Association between proteinuria and the development of malignant middle cerebral artery infarction: A retrospective cohort study

A disrupted blood-brain barrier (BBB) with extravasation of macromolecules plays a critical role in the development of malignant middle cerebral artery infarction (MMI). Proteinuria is considered a marker of generalized endothelial dysfunction, including BBB disruption. This study aimed to clarify whether proteinuria identified in the acute stage of stroke is associated with MMI development. Patients with infarctions involving the middle cerebral artery territory were reviewed. Urine samples collected within 8 hours after stroke were analyzed using urine dipsticks. Patients were divided into proteinuria (urine dipstick reading of 1 + to 4+) and nonproteinuria groups. MMI was present if either signs of uncal herniation or a progressive conscious disturbance were recorded along with a midline shift > 5 mm identified on follow-up computed tomography (CT). Among the 1261 patients identified between January 2010 and June 2019, 138 were eligible for final analyses. Patients in the MMI group had lower Alberta Stroke Program Early CT Scores (ASPECTS), higher National Institutes of Health Stroke Scale scores, and a greater proportion of proteinuria than those in the non-MMI group. Four multivariate logistic regression models were used to clarify the role of proteinuria in MMI development. In model 1, proteinuria was significantly associated with MMI after adjusting for age, sex, dyslipidemia and ASPECTS (OR = 2.987, 95% CI = 1.329–6.716, P = .0081). The risk of developing MMI in patients with proteinuria remained significant in model 2 (OR = 3.066, 95% CI = 1.349–6.968, P = .0075) after adjusting for estimated glomerular filtrate rate (eGFR) < 60ml/min/1.73 m(2) in addition to variables in model 1. In model 3, proteinuria was still significantly associated with MMI after adjusting for age, sex, dyslipidemia, ASPECTS, hypertension, diabetes, and atrial fibrillation (OR = 2.521, 95% CI = 1.075–5.912, P = .0335). In model 4, the risk of developing MMI in patients with proteinuria remained significant (OR = 2.579, 95% CI = 1.094–6.079, P = .0304) after adjusting for eGFR < 60ml/min/1.73 m(2) in addition to variables in model 3. Proteinuria is independently associated with MMI development. Proteinuria may be a clinically accessible predictor of MMI development.