Risk Prediction of Early and Late Acquired Glomerular and Tubular Dysfunctions in Patients with Disorders of Carbohydrate Metabolism

ORIGINAL ARTICLE
Marina A. Ustinova¹; Mikhail M. Batiushin, PhD, ScD¹; Sergey V.Vorobyev, PhD, ScD¹; Natalia A. Kuzmenko, PhD¹; Ekaterina Yu. Petrovskaya, PhD¹; Vladimir A. Chistyakov, PhD, ScD²; Vagif M. Ibragimov, PhD³; Irina V. Sarvilina, PhD, ScD^

¹Rostov-on-Don State Medical University, Rostov-on-Don; ²Laboratory of Experimental Mutagenesis, Academy of Biology and Biotechnology of Rostov-on-Don State Federal University, Rostov-on-Don; ³Dagestan State Medical University, Makhachkala; ^Medical Centre "Novomeditsina", Rostov-on-Don; the Russian Federation

*Corresponding author: Irina V. Sarvilina, PhD, ScD. General Director of Medical Centre «Novomeditsina», Rostov-on-Don, the Russian Federation. E-mail: isarvilina@mail.ru

Published: September 16, 2017.  doi: 10.21103/Article7(3)_OA9

Abstract: 

The purpose of this study was to create a new system for predicting the risk of glomerular and tubular dysfunctions (GTD) in patients with disorders of carbohydrate metabolism (DCM) based on standard parameters and new molecular markers for the development of kidney damage in patients with impaired glucose tolerance (IGT) and T2DM patients with diabetic nephropathy (DN).
Material and Methods: The study included 69 patients: 16 patients with IGT (Group 1), 28 T2DM patients with MAU (Group 2), and 25 T2DM patients with MacAU (Group 3), according to the inclusion/exclusion criteria in the research. All patients were stratified by the MDRD. The control group (Group 4) included 11 healthy individuals. The duration of DN was 10.5 years. At the stage of data collection and screening, the standard methods of identification of IGT, DM and DN were applied. Additional methods are included quantitative analysis of the level of α-GST and π-GST, MMP-9 in urine by ELISA.
Result: Analysis of the correlation interactions of the level of standard risk factors for the development of renal damage in patients with IGT and DN with the level of new molecular markers in urine and blood allows us to identify and introduce into clinical practice new screening tests reflecting the key molecular interactions that underlie the development of GTD in patients with DCM.

Keywords: 
diabetic nephropathy ● glomerular dysfunctions ● tubular dysfunctions ● molecular markers ● impaired glucose tolerance
References: 

1. Morley JE. Diabetes and aging: epidemiologic overview. Clin Geriatr Med. 2008;24(3):395-405. doi: 10.1016/j.cger.2008.03.005.
2. International Diabetes Federation. IDF Diabetes Atlas–7th Edition. Available from: http://www.diabetesatlas.org/.
3. Dell'Omo G, Penno G, Giorgi D, Di Bello V, Mariani M, Pedrinelli R. Association between high-normal albuminuria and risk factors for cardiovascular and renal disease in essential hypertensive men. Am J Kidney Dis. 2002; 40(1):1–8.
4. Garg J, Bakris G. Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. Vasc Med. 2002;7(1):35–43.
5. Wang XL, Lu JM, Pan CY, Tian H, Li CL. A comparison of urinary albumin excretion rate and microalbuminuria in various glucose tolerance subjects. Diabet Med. 2005;22(3):332–5.
6. Dedov I, Shestakova M, Mayorov A. Standards of specialized diabetes care. Edited by 8th Edition. Diabetes Mellitus 2017;20(1S):1-112. doi: 10.14341/DM20171S8.[in Russian].
7. Bahar A, Makhlough A, Yousefi A, Kashi Z, Abediankenari S. Correlation between prediabetes conditions and microalbuminuria. Nephrourol Mon. 2013 Spring; 5(2):741–4. doi:10.5812/numonthly.7646.
8. King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol. 1999;48(5):643–8.
9. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. N Engl J. Med. 2008;358(24):2560-72. doi: 10.1056/NEJMoa0802987.
10. Wood AJ, Churilov L, Perera N, Thomas D, Poon A, MacIsaac RJ, et al. Estimating glomerular filtration rate: Performance of the CKD-EPI equation over time in patients with type 2 diabetes. J Diabetes Complications. 2016;30(1):49-54. doi: 10.1016/j.jdiacomp.2015.08.025.
11. Hall JE, Brands MW, Dixon WN, Smith MJ Jr. Obesity-induced hypertension. Renal function and systemic hemodynamics. Hypertension.1993;22(3):292–9.
12. Rask-Madsen C, King G. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab. 2013;8(17):20-33. doi: 10.1016/j.cmet.2012.11.012.
13. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al.; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.
14. Kostadaras A. Risk Factors for Diabetic Nephropathy. Available from: http://www.kidneydoctor.com/dm.htm.
15. Stauffer ME, Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS One. 2014;9(1):e84943 doi: 10.1371/journal.pone.0084943.
16. American Diabetes Association. 15. Diabetes advocacy. Diabetes Care. 2017;40(Suppl 1):S128–S129.
17. Haneda M, Utsunomiya K, Koya D, Babazono T, Moriya T, Makino H, et al.; Joint Committee on Diabetic Nephropathy. A new Classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy. J Diabetes Investig. 2015; 6(2):242-6. doi: 10.1111/jdi.12319.
18. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, et al.Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters. Kidney Int. 2017; 92(1):26-36. doi: 10.1016/j.kint.2017.04.006.
19. Roshan B, Stanton RC. A story of microalbuminuria and diabetic nephropathy. J Nephropathology. 2013;2(4):234-40. doi:10.12860/JNP.2013.37.
20. Nordquist L, Wahren J. C-Peptide: the missing link in diabetic nephropathy? Rev Diabet Stud. 2009;6(3):203-10. doi 10.1900/RDS.2009.6.203
21. Dabla PK. Renal function in diabetic nephropathy. World J Diabetes. 2010; 1(2):48-56. doi:10.4239/wjd.v1.i2.48.
22. Sundberg AG, Appelkvist EL, Backman L, Dallner G. Urinary pi-class glutathione transferase as an indicator of tubular damage in the human kidney. Nephron.1994;67(3):308–16.
23. Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008;48:463–93.
24. Sharma M, Gupta S, Singh K, Mehndiratta M, Gautam A, Kalra O, et al. Association of glutathione-S-transferase with patients of type 2 diabetes mellitus with and without nephropathy. Diabetes Metab Syndr. 2016;10(4):194-197. doi: 10.1016/j.dsx.2016.06.006.

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International Journal of Biomedicine. 2017;7(3):208-212. ©2017 International Medical Research and Development Corporation. All rights reserved.