Abstract:Objective To investigate the longitudinal dynamic trajectories of urinary soluble CD 35-positive urinary extracellular vesicles（sCD35-uEV）, serum tumor necrosis factor-α（TNF-α）, and serum cystatin C（Cys C）inpatients with sepsis - associated acute kidney injury（SA-AKI）, and to evaluate their predictive value for 28-dayprognosis. Methods A total of 233 SA-AKI patients who met the diagnostic criteria and were admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from January 2023 to October 2025 were enrolled as study subjects. Using 28-day mortality as the prognostic endpoint, patients were divided into a survival group and a death group. Urine and blood samples were dynamically collected on day 1（T1）, day 3（T3）, day 5（T5）, and day 7（T7）after admission. Urinary sCD35-uEV and serum TNF-α were measured using enzyme-linked immunosorbent assay, and serum Cys C was measured using immunoturbidimetry. General data and longitudinal indicators were compared between the two groups. Multivariate logistic regression analysis was used to identify risk factors for 28-day mortality in SA-AKI patients, and a nomogram prediction model was established and validated. Results The 28-day all-cause mortality rate among the 233SA-AKI patients was 32.19%（75/233）. Compared with the survival group, the death group had a significantly higher age［（66.37±11.37）years vs（62.15±13.27）years, t=2.372, P=0.019］, Acute Physiology and Chronic Health Evaluation Ⅱ（APACHE Ⅱ）score（25.17±6.33 vs 22.47±5.74, t=3.241, P=0.001）, and Sequential Organ Fail are Assessment（SOFA）score（10.03±2.13 vs 8.95±1.89, t=3.893, P＜0.001）at admission. Over time, urinary sCD35-uEVlevels were consistently lower in the death group than in the survival group, repeated-measures ANOVA showed that serum TNF-α and Cys C levels were consistently higher in the death group, with a significant group-by-time interaction（P＜0.05）.From T3, the death group exhibited a longitudinal trajectory of persistently low expression of urinary sCD35-uEV and persistently high expression of serum TNF-α and Cys C. After adjusting for factors including age, multivariate logistic regression analysis showed that high APACHE Ⅱ score, high SOFA score, high TNF-α（T3）, and high Cys C（T3）were independent risk factors for 28-day mortality in SA-AKI patients, while high sCD35-uEV（T3）was a protective factor（P＜0.05）. Raceiver operating characteristic curve analysis showed that the area under the curve（AUC）values of APACHE Ⅱ score, SOFA score, sCD35-uEV（T3）, TNF-α（T3）, Cys C（T3）, and the nomogram model were 0.669, 0.769, 0.771, 0.763, 0.680, and 0.914, respectively. The DeLong test indicated that the AUC of the nomogram model was significantly higher than that of each individual factor（P＜0.05）.Bootstrap validation showed a concordance index of 0.828；the Hosmer-Lemeshow test yielded χ²=2.940, P=0.938, indicating good calibration of the nomogram model. When the threshold probability ranged from 0.14 to 0.86, the nomogram provided a positive net benefit. Conclusion The longitudinal trajectories of urinary sCD35-uEV as well as serum TNF-α and Cys C in SA-AKI patients are closely associated with prognosis. The nomogram model constructed based on day 3 indicators has significant clinical value for predicting 28-day mortality risk in SA-AKI patients.