Hao Fang, Zhang Shujun, Gao Yi
Department of Laboratory, Shanxi University of Traditional Chinese Medicine Affiliated Hospital Taiyuan 030024, Shanxi, China.
Am J Transl Res. 2024 Sep 15;16(9):5122-5129. doi: 10.62347/TOUH6376. eCollection 2024.
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).
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.
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).
SIRT6 and VNN1 are closely associated with AKI in children with PNS and may serve as valuable biomarkers for the diagnosis of AKI.
探讨沉默调节蛋白6（SIRT6）和血管生成素1（VNN1）在原发性肾病综合征（PNS）患儿外周血单核细胞中的诊断和预后价值及其与急性肾损伤（AKI）的相关性。
回顾性分析2021年12月至2023年12月在山西中医药大学附属医院诊断为PNS并接受治疗的101例患儿（观察组）。根据是否存在AKI，将这些患儿分为两组：AKI组（n = 35）和非AKI组（n = 66）。另外，选取同期进行体检的101例健康儿童作为对照组。采用蛋白质免疫印迹法和逆转录聚合酶链反应（RT-PCR）检测三组单核细胞中SIRT6和VNN1的蛋白质和mRNA水平。分析SIRT6和VNN1 mRNA水平与临床资料以及肾功能指标之间的相关性。采用受试者工作特征（ROC）曲线评估SIRT6和VNN1 mRNA水平对PNS患儿AKI的诊断价值。多因素logistic回归分析确定影响PNS患儿AKI的独立因素。还比较了PNS患儿治疗前后SIRT6和VNN1的mRNA水平。
与其他组相比，AKI组单核细胞中SIRT6的蛋白质和mRNA水平较低，而VNN1的蛋白质和mRNA水平较高（均P < 0.05）。相关性分析显示，SIRT6 mRNA水平与血清肌酐（Scr）、尿酸（UA）、血尿素氮（BUN）、24小时尿蛋白（24h UP）、胱抑素C（Cys-C）和β2-微球蛋白（β2-MG）呈正相关，但与白蛋白（ALB）和估计肾小球滤过率（eGFR）呈负相关（均P < 0.05）。相反，VNN1水平呈现相反的相关性（P < 0.05）。ROC曲线分析显示，单独使用SIRT6或VNN1 mRNA诊断AKI的曲线下面积（AUC）均高于0.8，联合诊断AUC超过0.9。logistic回归分析表明，eGFR、β2-MG、Cys-C以及SIRT6和VNN1的mRNA水平是PNS患儿发生AKI的独立危险因素（均P < 0.05）。治疗后，PNS患儿的SIRT6 mRNA水平显著降低，而VNN1 mRNA水平升高（均P < 0.05）。
SIRT6和VNN1与PNS患儿的AKI密切相关，可能作为诊断AKI的有价值生物标志物。
