Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity.Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

Among existing genetic and non-genetic models of obesity, the most widely used are the models of diet-induced obesity in rodents due to their relatively easy reproducibility and similarities to human pathogenesis of obesity. Within this review, we provide the analysis of diet-induced obesity models in rats, highlight attractive strengths as well as disadvantages of high-fat diets, fat or sugar choice diets, “cafeteria diets”, and “western diet”. Potential obesogenic mechanisms of the discussed models are analyzed. The directions of further studies required for an increase in reproducibility of experimental diet-induced obesity are proposed.

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.

Introduction: Insulin-like growth factor-1 (IGF-1) is a potent mitogen for glomerular mesangial cells which can stimulate cell migration and the production of fibronectin, proteoglycan, and type IV collagen, thereby promoting the development of the chronic kidney disease (CKD) in patients with diabetes. Objectives: The aim of the study was to assess the associations between serum levels of IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) and CKD in diabetic patients. Patients and Methods: We investigated 102 Belarusian men and women with diabetes type 2 aged 56.67±0.81 years. Control group included 68 healthy people the same age. We estimated GFR with the use of the CKD-EPI creatinine-cystatin C equation to determine eGFRcr_cys. Serum total IGF-1 and IGFBP-3 levels were measured using immunoradiometric assay (IRMA) (Beckman Coulter, Czech Republic s.r.o.). Results: Patients with diabetes had significantly lower level of IGF-1 than controls. However, IGFBP-3 levels were similar in the two groups. Diabetic patients with CKD had significantly higher levels of IGF-1 and IGFBP-3 than diabetic patients without CKD (P=0.0031). However, according to multivariate analysis, only IGF-1 and cystatin C were associated with renal impairment. In detail, the odds of having eGFR<60 mL/min/1.73 m² increased with rising IGF-1 levels (OR: 1.025, [CI 1.002-1.048]). Conclusion: Our study revealed that higher serum IGF-1 levels were positively associated with CKD in patients with diabetes. We suggest that IGF-1 might be a predictor of CKD in patients with diabetes. Further research is necessary to confirm the observed this association and to detect the causal relations.

Spina bifida is a developmental defect of the spinal cord and/or spinal cord that results from abnormal closure of the embryonic neural tube. Many factors have been described to determine the risks of developing this pathology, but the incidence of the defect is still high. 61% of patients with spina bifida have neurogenic bladder dysfunction based on intravesical hypertension, which contributes to reverse urethral flow and vesico-uretero-renal reflux, associated with chronic inflammatory and obstructive diseases of the urinary tract. Between 25-50% of patients with spina bifida develop chronic kidney disease, significantly reducing their quality of life. In some types of Spina bifida, urological symptoms may be prominent and indicate the presence of this malformation. Therefore, early diagnosis of Spina bifida and timely prophylactic and therapeutic measures are particular importance. This article describes a clinical case of Spina bifida posterior L1-L2 with a closed L1-L2 meningocele in which urological symptoms were the dominant manifestation. The development of secondary complications of neurogenic bladder in the presented patient cannot be excluded, which requires closer monitoring.