The role of inflammatory markers and growth factors in progression of chronic kidney disease in patients with diabetes mellitus

Abstract

Introduction: A Diabetes mellitus (DM) and chronic kidney disease (CKD) are two chronic non-communicable diseases that have exceeded epidemic thresholds in all countries of the world. The problem of early diagnosis, prevention and treatment of CKD continues to be relevant for modern medicine, and assessment of the severity of CKD and associated cardiovascular complications is of great practical importance for primary and secondary prevention. Objectives: The aim of the study was to assess the role of proinflammatory cytokines, chemokines and growth factors in progression of CKD in patients with DM. Patients and Methods: We screened 155 type 2 DM patients aged 65.00 (55.00-71.00) years. Control group included 21 healthy people with the same age. Renal function was assessed based on the levels of serum creatinine, cystatin C, estimated glomerular filtration rate (eGFR), which was calculated according to the CKD-EPI (chronic kidney disease epidemiology collaboration) equation, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). The analysis of serum and urine biomarkers was carried out by enzyme immunoassay using commercial test systems. Results: Patients with DM had significantly higher levels of proinflammatory cytokines in comparison with the control group. The levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor-23 (FGF-23), regulated upon activation, normal T cell expressed and presumably secreted (RANTES), MIG, CRP, kidney injury molecule-1 (KIM-1) and homocysteine gradually increased with decreasing GFR. According to the results of univariate linear regression analysis, there were significant relationships between the levels of VEGF-A, FGF-23, RANTES, tumor necrosis factor alpha (TNF-alpha), MIG, CRP, hs-CRP, IL-6 and renal function. By multiple linear regression analysis adjusted for confounding factors, serum creatinine was significantly correlated with FGF-23 (β=0.40, P<0.001) and Il-6 (β=0.29, P<0.001). Conclusion: Our study demonstrated the important role of growth factors and proinflammatory cytokines in the development and progression of CKD in DM. However, despite these data, the pathogenesis of diabetic changes in the kidneys remains not fully understood and, in order to clarify the possibility of pathogenetic influences on the progression of diabetic nephropathy, it is necessary to study various aspects of its development, including genetic factors.