Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes’ distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p < 0.001, p < 0.001, p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances.

Purpose: Diabetic kidney disease (DKD) significantly affects health and healthcare costs due to chronic kidney disease complications. Given asprosin’s potential as a biomarker for disease progression, we conducted the first systematic review and meta-analysis on its relationship with DKD in adults with type 2 diabetes mellitus (T2DM). Methods: PubMed, Embase, Cochrane, and Web of Science were systematically searched. Standard mean differences (SMD) with 95% confidence intervals (CI) and Fisher’s Z transformation were used to examine the relationship between asprosin and DKD. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) and its version for cross-sectional studies. Heterogeneity (I² > 50%) was analyzed with a random-effects model. Results: Six studies (n = 1340) were included. Meta-analysis results indicated that T2DM patients with DKD (micro/macroalbuminuria) had significantly higher circulating asprosin levels than normoalbuminuric T2DM patients (SMD: 1.5, 95% CI: 0.69– 2.32, p = 0.0003). Meta-analysis of correlation revealed a positive association of asprosin with urinary albumin excretion ratio (UACR) (Fisher’s Z = 0.4; 95% CI: 0.240– 0.554, p < 0.001) and body mass index (BMI) (Fisher’s Z = 0.17; 95% CI: 0.036– 0.301, p = 0.013), and a negative association with estimated glomerular filtration rate (eGFR) (Fisher’s Z = − 0.35; 95% CI: − 0.471 to − 0.239, p < 0.001). Conclusion: Asprosin is elevated in T2DM patients with pre-DKD (early stage DKD) and DKD and correlates with key markers of disease severity. Additional research is required to better understand the pathophysiological mechanisms of asprosin and its role in DKD.

Introduction/Objective. The aim of the study was to examine the progression of diabetic nephropathy (DN) in a prospective three-year period as well as to establish the risk factors for DN progression. Methods. The study involved 45 patients with type 2 diabetes and DN (26 males, aged 18-62 years) followed for three years. All patients underwent physical examination and laboratory analysis at each visit. Laboratory analyses included complete blood count, serum glucose, urea, creatinine, protein, lipid concentration, glycosylated hemoglobin (HbA1c) and urine protein, albumin and creatinine concentration. Glomerular filtration rate (GFR) was calculated using Modification of Diet in Renal Disease formula. Kidney length and parenchymal thickness were measured by ultrasound. Results. Fasting serum glucose concentration (12.0 ± 2.79 vs. 9.50 ± 2.22, p < 0.001) and HbA1c (7.99 ± 1.43 vs. 7.49 ± 1.29, p < 0.031) were decreased over the three years. Albuminuria increased (43.75 ± 10.83 vs. 144.44 ± 52.70 mg/l, p < 0.001) and GFR (63 vs. 58.3 ml/min/1,73m2) decreased significantly during the study, but serum lipid concentration remained unchanged. Mean kidney length and parenchymal thickness decreased during the three years. Linear regression analysis found systolic blood pressure, fasting glycemia, HbA1c as positive and kidney length and parenchymal thickness as negative predictors of proteinuria increase, but proteinuria as negative and serum iron and albumin concentrations as positive predictors of annual change in GFR. Conclusion. High blood pressure and high HbA1c are selected as significant risk factors for increasing of proteinuria which is a significant predictor of GFR decreasing in patients with DN.

Aims: The aim of this study was to compare the risk factors and prevalence of vascular calcification (VC) in pre-dialysis and hemodialysis (HD) patients with Balkan endemic nephropathy (BEN) or other kidney diseases (non-BEN). Materials and Methods: The study involved 115 patients, 32 pre-dialysis and 83 HD patients, separated into groups of BEN and non-BEN patients. In addition to interviews, objective examinations and laboratory analyses, VC was assessed using Adragao score. Results: Patients with BEN were significantly older in both groups, while pre-dialysis BEN patients had significantly lower systolic blood pressure, serum cholesterol and phosphorus levels, but higher urinary excretion of phosphorus than non-BEN patients. These differences were lost in HD groups. In pre-dialysis patients, prevalence of VC was lower in BEN than in non-BEN group and mean VC score differed significantly between them (2.8 (1.7) vs. 4.6 (1.8); p = 0.009). No significant difference in VC score was found between BEN and non-BEN patients on HD. Multivariate analysis showed that in pre-dialysis patients VC score >4 was associated with lower iPTH and higher serum cholesterol level, but in the HD group with higher serum triglyceride level and longer HD vintage. Conclusions: Lower prevalence of risk factors for VC in the BEN than non-BEN patients was found in pre-dialysis but not in HD group and this was reflected in the prevalence and severity of VC in the groups. Prevalence of VC and mean VC score were significantly lower in pre-dialysis BEN than in non-BEN patients but not for those on HD.