Features of the course of the nephropathy in patients with type 2 diabetes mellitus: genetic aspects and angiogenesis

Abstract

Objective — to determine serum level of vascular endothelial growth factor (VEGF) in patients with diabetic nephropathy (DN) — carriers of different genotypes of Klotho gene polymorphism in different stages of the disease and in the treatment dynamics.Materials and methods. The examinations involved 84 patients (38 men and 46 women) with type 2 diabetes mellitus (DM 2). Depending on the functional state of kidneys, patients were divided into two groups: Group I — patients with normal glomerular filtration rate (GFR) and albuminuria (n = 46), group II — patients with the reduced GFR and albuminuria (n = 38). The control group consisted of 40 healthy individuals. DNA amplification and genotyping of the Klotho gene polymorphism were performed by real-time PCR. VEGF concentration was determined by enzyme-linked immunosorbent assay before and after 6 months of pathogenetic therapy, which included: antidiabetic drugs, ACE inhibitor or angiotensin II receptor blocker and coenzyme A reductase inhibitor.Results. In patients with DN, a significant increase of serum VEGF levels was determined, which was closely related to the functional state of the kidneys. The VEGF level was 162.63 ± 0.31 pg/ml in DN with albuminuria and normal GFR, 367.43 ± 36.15 pg/ml in DN with decreased GFR. The highest response to pathogenetic treatment was observed in the group with the initial stages of nephropathy — the level of VEGF decreased by 28 %, while in the group with low GFR — only by 16 %.Conclusions. It has been established that carriers of the heterozygous genotype of the F352V polymorphism of the Klotho gene had significantly lower serum VEGF levels when compared to the common F352F genotype. Blood VEGF levels in patients with DN can serve as an integral marker of endothelial dysfunction and pathological angiogenesis. After 6 months of pathogenetic nephroprotective therapy serum VEGF levels decreased significantly in all groups of patients with DN.