The study aimed to assess serum Klotho protein level in type 2 diabetic patients depending on kidney function. Methods. This observational study included 72 patients with diabetes mellitus (DM) and 26 patients with acute coronary syndrome. The control group consisted of 20 healthy subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR), the diabetics were divided into the following groups: group I included the patients with normal GFR and without albuminuria (n = 25); group ІІ consisted the patients with normal GFR and albuminuria (n = 23); group III – the patients with reduced GFR and albuminuria (n = 24) and group ІV included the patients with acute coronary syndrome (n = 26). The GFR was calculated using the CKD EPI formula (KDIGO 2012). The concentration of Klotho protein was determined by enzyme-linked immunosorbent assay. Results. The development of diabetic nephropathy in type 2 diabetic patients accompanied by a significant decrease of soluble Klotho compared with the controls and the patients of the1-st group. The level of Klotho protein in the group of patients with albuminuria decreased to (490.66 ± 58.76) pg/ml (p <0.05). The lowest concentration of Klotho (443.58 ± 46.92) pg/ml was found in the advanced stages of diabetic nephropathy, namely in patients with albuminuria and impaired renal function. Moreover, a significantly decreased serum Klotho was observed in acute coronary syndrome group in comparison with the control group (p <0.05). There were inverse correlations of Klotho concentration with urinary albumin and blood creatinine levels and a direct correlation between Klotho and GFR. Conclusions. The obtained data indicated the key role of Klotho protein in the formation of renal pathology in type 2 diabetes and the feasibility of practical use of Klotho determination as an early diagnostic marker of renal disorders and cardiovascular risk assessment. The strategies improving Klotho production may be useful in the reduction of both renal and vascular lesions progression in type 2 diabetic patients.

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The goal of many studies around the world is to find preventive agents that may slow the progression of diabetic nephropathy in patients with type 2 diabetes mellitus at different stages of the disease, accordingly to preventing the progression of chronic kidney disease. The purpose of the work was to study the effect of complex nephroprotective therapy with the use of an inhibitor of the sodium glucose co-transporter 2 and spathogenetic therapy on metabolic parameters and the level of vasculoendothelial growth factor in blood serum of diabetic nephropathy patients at different stages of the disease. Materials and methods. 78 patients with type 2 diabetes mellitus were examined. Depending on the presence of albuminuria and glomerular filtration rate level, patients with diabetes mellitus were divided into the following groups: group I – patients with type 2 diabetes mellitus with normal glomerular filtration rate and albuminuria (n=62), group II – patients with type 2 diabetes mellitus with decreased glomerular filtration rate and albuminuria (n=16). The concentration of the vasculoendothelial growth factor was determined by enzyme-linked immunosorbent assay before and after 12 months of pathogenetic therapy. The glomerular filtration rate was calculated using the CKD EPI formula (KDIGO 2012). Patients of the first cohort received basic therapy, which included: blockers of the renin-angiotensin-aldosterone system, a coenzyme A reductase inhibitor and metformin, patients of the second cohort additionally received a sodium glucose co-transporter 2 inhibitor. Results and discussion. A decrease in vasculoendothelial growth factor levels in blood serum was found in all groups of examined patients, both under the influence of standard nephroprotective therapy, and with the use of complex treatment with an additional prescription of the sodium glucose co-transporter 2 inhibitor dapagliflozin. The highest level of response to treatment was observed in the group with the early stages of nephropathy. The therapy led to a significant improvement in the lipid spectrum of blood serum (increase of high-density lipoprotein cholesterol, decrease of total cholesterol, triglycerides and low-density lipoproteins) in all study groups. Conclusion. A decrease in serum vasculoendothelial growth factor levels against the background of an improvement in the basic clinical and laboratory parameters indicates not only an improvement kidneys function, but also a decrease in cardiovascular risk in this category of patients. The results of investigation indicate the feasibility of practical use of study vasculoendothelial growth factor serum level of diabetic nephropathy patients as an early diagnostic marker of cardiac disorders, prognosis assessment and improvement of the cardionephroprotective strategy

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Abstract. The aim of the study was to assess a serum level of vascular endothelial growth factor (VEGF) in type 2 diabetic patients depending on kidney function. Methods: we examined 66 type 2 diabetic patients and 20 healthy control subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR) level, patients with diabetes mellitus (DM) were divided into the following groups: group I - patients with type 2 DM without signs of nephropathy – normal GFR without albuminuria (n = 26); group ІІ - patients with type 2 DM with normal GFR and albuminuria (n = 22); group III - patients with type 2 DM with reduced GFR and albuminuria (n = 18). ІV group - patients with acute coronary syndrome (n = 26). The concentration of the VEGF was determined by enzyme-linked immunosorbent assay. The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012). Results: serum VEGF level in patients with diabetic nephropathy (DN) was significantly increased depending on kidney function. VEGF positively correlated with urine albumin and serum creatinine levels and the negative correlation with GFR was found. These findings prove the undeniable role of kidneys in the development of renocardial syndrome in patients with DN. VEGF levels positively correlated with glycosylated hemoglobin and total cholesterol, indicating an unconditional dependence of endothelial dysfunction on lipid and glucose metabolism disorders. Conclusions: Increased levels of VEGF in type 2 diabetic patients without clinical signs of kidney damage may indicate the development of subclinical renal dysfunction. Blood VEGF in patients with DN may be an integral marker of endothelial dysfunction and pathological angiogenesis. Our findings suggest that determination of serum VEGF level in patients with DN may have practical use as an early predictor of cardiac disruption, estimation of the prognosis, as well as improvement of cardionephroprotective strategy.