Background and Objective: The similarities in organizational structure and microenvironment between the brain and kidneys suggest the potential utility of kidney biomarkers in the detection of cerebrovascular diseases. Cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL), well-established sensitive biomarkers of kidney injury, may also recognize as indicators of neuroinflammation. However, their diagnostic capabilities for ischemic stroke (IS) attacks under different kidney function states remain unclear. This case-control study aims to evaluate the diagnostic value of serum kidney biomarkers for ischemic stroke (IS) attack, with focus on NGAL and CysC. Methods: A total of 498 patients with first IS attack, 173 patients with risk-related diseases (designated as the disease control DC group), and 293 healthy subjects (serving as the healthy control HC group) were enrolled. A comprehensive comparative analysis was performed to examine the associations between common kidney biomarkers (Specifically, NGAL and CysC) and IS. Results: Serum NGAL levels were significantly elevated in patients with first IS compared with both the HC group (z=5.964, P 0.05); 2) among IS patients with chronic kidney disease (CKD), CysC showed the highest partial correlation (r partial =0.460, P< 0.001), followed by estimated glomerular filtration rate (r partial =− 0.373, P< 0.001), creatinine (r partial =0.279, P< 0.001), NGAL (r partial =0.233, P< 0.001), and urea (r partial =0.182, P< 0.001). Stratified multiple linear regression analysis based on kidney impairment demonstrated: 1) in patients with preserved kidney function, only NGAL was correlated with IS risk (OR=6.54, P< 0.001), with moderate diagnostic effect (AUC=0.734, P< 0.001); and 2) for CKD patients, CysC outperformed NGAL in diagnosing IS attack, demonstrating a stronger correlation with IS risk (OR=5.97, P< 0.001) and a higher discriminatory ability (AUC=0.835, P< 0.001). Conclusion: IS is intricately linked to both kidney injury and neuroinflammation. NGAL and CysC serve as appropriate biomarkers for diagnosing IS attack in patients with normal kidney function and those with CKD, respectively. Respective monitoring of CysC and NGAL in individuals with and without CKD could facilitate early diagnosis, prevention and targeted management of stroke in high-risk populations. Keywords: ischemic stroke, neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury, neuroinflammation
Jin et al. (2026) studied this question.