Expression of SIRT6 and VNN1 in children with primary nephrotic syndrome and their correlation with acute kidney injury

摘要

Objective: To explore the diagnostic and prognostic values of Sirtuin 6 (SIRT6) and Vanin-1 (VNN1) in peripheral blood monocytes of children with primary nephrotic syndrome (PNS) and their correlation with acute kidney injury (AKI). Methods: A retrospective analysis was conducted on 101 children (observation group) diagnosed with PNS and treated at the Shanxi University of Traditional Chinese Medicine Affiliated Hospital from December 2021 to December 2023. These children were categorized into two groups: the AKI group (n=35) and the non-AKI group (n=66), based on the presence of AKI. Additionally, 101 healthy children who underwent physical examinations during the same period served as the control group. Western blotting and RT-PCR were employed to measure the protein and mRNA levels of SIRT6 and VNN1 in monocytes across the three groups. The correlation between SIRT6 and VNN1 mRNA levels and clinical data, as well as kidney function indicators, was analyzed. The diagnostic value of SIRT6 and VNN1 mRNA levels for AKI in PNS was assessed using ROC curves. Multivariate logistic regression identified independent factors influencing AKI in PNS. The mRNA levels of SIRT6 and VNN1 were also compared before and after treatment in children with PNS. Results: The AKI group exhibited lower SIRT6 protein and mRNA levels, and higher VNN1 protein and mRNA levels in monocytes compared to the other groups (all P<0.05). Correlation analysis revealed that SIRT6 mRNA levels were positively correlated with serum creatinine (Scr), uric acid (UA), blood urea nitrogen (BUN), 24-hour urine protein (24h UP), cystatin C (Cys-C), and β2-microglobulin (β2-MG), but negatively correlated with albumin (ALB) and estimated glomerular filtration rate (eGFR) (all P<0.05). In contrast, VNN1 levels showed the opposite correlations (P<0.05). ROC curve analysis showed that the AUC for SIRT6 or VNN1 mRNA alone in diagnosing AKI was above 0.8, with a combined diagnostic AUC exceeding 0.9. Logistic regression indicated that eGFR, β2-MG, Cys-C, and the mRNA levels of SIRT6 and VNN1 were independent risk factors for AKI in PNS (all P<0.05). After treatment, SIRT6 mRNA levels significantly decreased, while VNN1 mRNA levels increased in children with PNS (both P<0.05). Conclusion: SIRT6 and VNN1 are closely associated with AKI in children with PNS and may serve as valuable biomarkers for the diagnosis of AKI.