Value of urinary adiponectin, VCAM-1 and RBP 4 in early diagnosis of kidney damage in children with type 1 diabetes mellitus

Authors

DOI:

https://doi.org/10.14739/2310-1210.2021.1.224886

Keywords:

diabetes mellitus, diabetic nephropathy, children, biomarkers, adiponectin, VCAM-1, RBP 4

Abstract

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

  1. International Diabetes Federation. (2019). IDF Diabetes Atlas 9th edition 2019. https://diabetesatlas.org/en/
  2. 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
  3. 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
  4. 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
  5. 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
  6. Fang, H., & Judd, R. L. (2018). Adiponectin Regulation and Function. Comprehensive Physiology, 8(3), 1031-1063. https://doi.org/10.1002/cphy.c170046
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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

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Published

2021-04-07

How to Cite

1.
Vikhrova IO, Loboda AM. Value of urinary adiponectin, VCAM-1 and RBP 4 in early diagnosis of kidney damage in children with type 1 diabetes mellitus . Zaporozhye Medical Journal [Internet]. 2021Apr.7 [cited 2026May16];23(1):72-6. Available from: https://zmj.zsmu.edu.ua/article/view/224886

Issue

Vol. 23 No. 1 (2021)

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Original research

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