» Articles » PMID: 39398594

Expression of SIRT6 and VNN1 in Children with Primary Nephrotic Syndrome and Their Correlation with Acute Kidney Injury

Overview
Journal Am J Transl Res
Specialty General Medicine
Date 2024 Oct 14
PMID 39398594
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Expanding the clinical spectrum of 19p13.3 microduplication syndrome: a case report highlighting nephrotic syndrome and literature review.

Sun W, Yan H, Sun M, Wang J, Li K BMC Pediatr. 2025; 25(1):70.

PMID: 39875952 PMC: 11773902. DOI: 10.1186/s12887-025-05394-1.

References
1.
Xu Y, Huang Y, Zhang C, Sun L, Sun Z, Wang L . Efficacy and safety of rituximab for primary nephrotic syndrome with acute kidney injury: A two-center prospective cohort study. Clin Immunol. 2022; 246:109211. DOI: 10.1016/j.clim.2022.109211. View

2.
Karami M, Mehrabi F, Allameh A, Pahlevan Kakhki M, Amiri M, Emami Aleagha M . Klotho gene expression decreases in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting multiple sclerosis. J Neurol Sci. 2017; 381:305-307. DOI: 10.1016/j.jns.2017.09.012. View

3.
Yang Q, Hu J, Yang Y, Chen Z, Feng J, Zhu Z . Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics. 2020; 10(16):7465-7479. PMC: 7330847. DOI: 10.7150/thno.45003. View

4.
Aydin F, Eynel E, Oruc I, Ince H, Yuksel E, Aydin E . The Role of Monocyte to High-Density Lipoprotein Cholesterol Ratio in Predicting the Severity of Proteinuria and Renal Dysfunction in Primary Nephrotic Syndrome. Cureus. 2022; 13(12):e20345. PMC: 8752344. DOI: 10.7759/cureus.20345. View

5.
Watanabe A, Guaragna M, Santoro Belangero V, Casimiro F, Bosco Pesquero J, de Santis Feltran L . APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses. Pediatr Nephrol. 2021; 36(8):2327-2336. DOI: 10.1007/s00467-021-04960-w. View