Value of urinary adiponectin, VCAM-1 and RBP 4 in early diagnosis of kidney damage in children with type 1 diabetes mellitus
DOI:
https://doi.org/10.14739/2310-1210.2021.1.224886Keywords:
diabetes mellitus, diabetic nephropathy, children, biomarkers, adiponectin, VCAM-1, RBP 4Abstract
Aim. The aim of the current study was to investigate urinary adiponectin, VCAM-1, and RBP 4 levels in children depending on the diabetes duration.
Materials and methods. The study involved 55 subjects, including 47 children with type 1 diabetes mellitus and eight children without diabetes and kidney disease history. Participants with diabetes were stratified into three groups, depending on the diabetes duration: <1 year (11 people), 1–5 years (24 people) and >5 years (12 people). According to the Order of the Ministry of Health of Ukraine, dated April 27, 2006, No. 254 on providing medical care to children in the specialty “Pediatric Endocrinology”, we examined the children and diagnosed type 1 diabetes mellitus. Chemiluminescence signals of adiponectin, VCAM-1, and RBP4 in urine were analyzed with Bio-Rad ChemiDoc Touch using a Proteome Profiler Human Kidney Biomarker Antibody Array (R&D Systems, Minneapolis, USA). We used descriptive statistics and nonparametric methods (contingency tables and Spearman’s rank correlation coefficient (r)) for the statistical analysis of study materials. Statistically significant differences were indicated by P values <0.05.
Results. Urinary adiponectin, VCAM-1, and RBP 4 levels statistically increased within the first year after diagnosing type 1 diabetes in children. Adiponectin was strongly correlated with VCAM-1 (r = 0.636, P = 0.026), and RBP 4 (r = 0.650, P = 0.022). Urinary adiponectin levels showed a statistically significant correlation with GFR (r = 0.007).
Conclusions. Serum creatinine and GFR are ineffective as diagnostic indicators of kidney damage in children with diabetes mellitus at the incipient stages. Adiponectin in children’s urine can be used as a non-invasive kidney damage marker in the early years of type 1 diabetes. Adiponectin, VCAM-1, and RBP 4 measurements would allow an early prediction and evaluation of both tubular and glomerular kidney damage in children with diabetes.
References
International Diabetes Federation. (2019). IDF Diabetes Atlas 9th edition 2019. https://diabetesatlas.org/en/
Dabelea, D., Stafford, J. M., Mayer-Davis, E. J., D'Agostino, R., Jr, Dolan, L., Imperatore, G., Linder, B., Lawrence, J. M., Marcovina, S. M., Mottl, A. K., Black, M. H., Pop-Busui, R., Saydah, S., Hamman, R. F., Pihoker, C., & SEARCH for Diabetes in Youth Research Group. (2017). Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood. JAMA, 317(8), 825-835. https://doi.org/10.1001/jama.2017.0686
Campion, C. G., Sanchez-Ferras, O., & Batchu, S. N. (2017). Potential Role of Serum and Urinary Biomarkers in Diagnosis and Prognosis of Diabetic Nephropathy. Canadian Journal of Kidney Health and Disease, 4, Article 2054358117705371. https://doi.org/10.1177/2054358117705371
Al-Rubeaan, K., Siddiqui, K., Al-Ghonaim, M. A., Youssef, A. M., Al-Sharqawi, A. H., & AlNaqeb, D. (2017). Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients. Scientific Reports, 7(1), Article 2684. https://doi.org/10.1038/s41598-017-02421-9
Bjornstad, P., Pyle, L., Kinney, G. L., Rewers, M., Johnson, R. J., Maahs, D. M., & Snell-Bergeon, J. K. (2017). Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. Journal of Diabetes and its Complications, 31(2), 369-374. https://doi.org/10.1016/j.jdiacomp.2016.06.012
Fang, H., & Judd, R. L. (2018). Adiponectin Regulation and Function. Comprehensive Physiology, 8(3), 1031-1063. https://doi.org/10.1002/cphy.c170046
Mok, C. C., Soliman, S., Ho, L. Y., Mohamed, F. A., Mohamed, F. I., & Mohan, C. (2018). Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis. Arthritis Research & Therapy, 20(1), Article 6. https://doi.org/10.1186/s13075-017-1498-3
Kong, D. H., Kim, Y. K., Kim, M. R., Jang, J. H., & Lee, S. (2018). Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. International Journal of Molecular Sciences, 19(4), Article 1057. https://doi.org/10.3390/ijms19041057
Guillén-Gómez, E., Bardají-de-Quixano, B., Ferrer, S., Brotons, C., Knepper, M. A., Carrascal, M., Abian, J., Mas, J. M., Calero, F., Ballarín, J. A., & Fernández-Llama, P. (2018). Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy. Journal of Diabetes Research, 2018, Article 6165303. https://doi.org/10.1155/2018/6165303
Fiseha, T., & Tamir, Z. (2016). Urinary Markers of Tubular Injury in Early Diabetic Nephropathy. International Journal of Nephrology, 2016, Article 4647685. https://doi.org/10.1155/2016/4647685
Mahfouz, M. H., Assiri, A. M., & Mukhtar, M. H. (2016). Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Retinol-Binding Protein 4 (RBP4) in Type 2 Diabetic Patients with Nephropathy. Biomarker Insights, 11, 31-40. https://doi.org/10.4137/BMI.S33191
Ministry of Health of Ukraine. (2006, April 27). Pro zatverdzhennia protokoliv nadannia medychnoi dopomohy ditiam za spetsialnistiu "Dytiacha endokrynolohiia" [About the statement of protocols of providing medical care to children on a specialty "Children's endocrinology" (No. 254)]. https://zakon.rada.gov.ua/rada/show/v0254282-06#Text
Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics of North America, 39(3), 481-497. https://doi.org/10.1016/j.ecl.2010.05.011
Lovshin, J. A., Škrtić, M., Bjornstad, P., Moineddin, R., Daneman, D., Dunger, D., Reich, H. N., Mahmud, F., Scholey, J., Cherney, D., & Sochett, E. (2018). Hyperfiltration, urinary albumin excretion, and ambulatory blood pressure in adolescents with Type 1 diabetes mellitus. American Journal of Physiology. Renal Physiology, 314(4), F667-F674. https://doi.org/10.1152/ajprenal.00400.2017
Uwaezuoke, S. N. (2017). The role of novel biomarkers in predicting diabetic nephropathy: a review. International Journal of Nephrology and Renovascular Disease, 10, 221-231. https://doi.org/10.2147/IJNRD.S143186
Sharaf El Din, U., Salem, M. M., & Abdulazim, D. O. (2017). Diabetic nephropathy: Time to withhold development and progression - A review. Journal of Advanced Research, 8(4), 363-373. https://doi.org/10.1016/j.jare.2017.04.004
Nauta, F. L., Boertien, W. E., Bakker, S. J., van Goor, H., van Oeveren, W., de Jong, P. E., Bilo, H., & Gansevoort, R. T. (2011). Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care, 34(4), 975-981. https://doi.org/10.2337/dc10-1545
Rutkowski, J. M., Wang, Z. V., Park, A. S., Zhang, J., Zhang, D., Hu, M. C., Moe, O. W., Susztak, K., & Scherer, P. E. (2013). Adiponectin promotes functional recovery after podocyte ablation. Journal of the American Society of Nephrology, 24(2), 268-282. https://doi.org/10.1681/ASN.2012040414
Cammisotto, P. G., & Bendayan, M. (2008). Adiponectin stimulates phosphorylation of AMP-activated protein kinase alpha in renal glomeruli. Journal of Molecular Histology, 39(6), 579-584. https://doi.org/10.1007/s10735-008-9198-6
Ayed, M. H., Amar, B. E., Omar, E. F., Walid, G. B., Njood, M. A., & Hassan, E. E. (2018). Study of Circulating Adiponectin Level in Children with Type 1 Diabetes Mellitus in Najran-KSA. Current Research in Diabetes & Obesity Journal, 9(1), Article 555755. https://doi.org/10.19080/CRDOJ.2018.09.555755
Yamakado, S., Cho, H., Inada, M., Morikawa, M., Jiang, Y. H., Saito, K., Nakaishi, K., Watabe, S., Takagi, H., Kaneda, M., Nakatsuma, A., Ninomiya, M., Imachi, H., Arai, T., Yoshimoto, T., Murao, K., Chang, J. H., Chen, S. M., Shih, Y. C., Zeng, M. J., … Ito, E. (2019). Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy. BMJ Open Diabetes Research & Care, 7(1), Article e000661. https://doi.org/10.1136/bmjdrc-2019-000661
Lin, J., Glynn, R. J., Rifai, N., Manson, J. E., Ridker, P. M., Nathan, D. M., & Schaumberg, D. A. (2008). Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial. Diabetes Care, 31(12), 2338-2343. https://doi.org/10.2337/dc08-0277
Liu, J. J., Yeoh, L. Y., Sum, C. F., Tavintharan, S., Ng, X. W., Liu, S., Lee, S. B., Tang, W. E., Lim, S. C., & SMART2D study. (2015). Vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1, is associated with diabetic kidney disease in Asians with type 2 diabetes. Journal of Diabetes and its Complications, 29(5), 707-712. https://doi.org/10.1016/j.jdiacomp.2015.02.011
Polat, S. B., Ugurlu, N., Aslan, N., Cuhaci, N., Ersoy, R., & Cakir, B. (2016). Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus. Archives of Endocrinology and Metabolism, 60(2), 117-124. https://doi.org/10.1590/2359-3997000000116
Yang, Q., Graham, T. E., Mody, N., Preitner, F., Peroni, O. D., Zabolotny, J. M., Kotani, K., Quadro, L., & Kahn, B. B. (2005). Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436(7049), 356-362. https://doi.org/10.1038/nature03711
Park, S. E., Lee, N. S., Park, J. W., Rhee, E. J., Lee, W. Y., Oh, K. W., Park, S. W., Park, C. Y., & Youn, B. S. (2014). Association of urinary RBP4 with insulin resistance, inflammation, and microalbuminuria. European Journal of Endocrinology, 171(4), 443-449. https://doi.org/10.1530/EJE-14-0247
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
