Profile of urinary exosomal microRNAs and their contribution to diabetic kidney disease through a predictive classification model.

AIM: Evaluate the expression of exomiRs-126, -146, and -155 in urinary exosomes of patients with T2DM and diabetic kidney disease to establish a predictive classification model with exomiRs and clinical variables in order to determine their contribution to DKD. METHODS: The study group included 92 subjects: 64 patients diagnosed with T2DM subclassified into two groups with albuminuria (T2DM with albuminuria, n = 30) and without albuminuria (TD2M, n = 34) as well as 28 healthy, non-diabetic participants. Exosomes were isolated from urine and identified by TEM and flow cytometry. Profile expression of exomiRs-126, -146 and -155 was evaluated by RT-qPCR. Data were analysed by permutational multivariate analysis of variance (PERMANOVA), similarity percentage (SIMPER), principal coordinate analysis (PCO), and canonical analysis of principal coordinates (CAP). RESULTS: T2DM patients with and without albuminuria showed higher levels of miR-155 and miR-146 compared with controls. In addition, T2DM patients with albuminuria presented a significant increase in miR-126 contrasted to controls and patients without albuminuria. PCO analysis explained 34.6% of the total variability of the data (PERMANOVA; p < .0001). Subsequently, SIMPER analysis showed that miR-146, miR-155, and miR-126 together, with some clinical parameters, contributed to 50% of the between-group significance. Finally, the CAP analysis developed showed a correct classification of 89.01% with the analysed parameters. CONCLUSION: A platform using a combination of clinical variables and exomiRs could be used to classify individuals with T2D as risk for developing DKD.

Identification of metabolic markers in patients with type 2 Diabetes by Ultrafast gas chromatography coupled to electronic nose. A pilot study.

Metabolomics is a potential tool for the discovery of new biomarkers in the early diagnosis of diseases. An ultra-fast gas chromatography system equipped to an electronic nose detector (FGC eNose) was used to identify the metabolomic profile of Volatile Organic Compounds (VOCs) in type 2 diabetes (T2D) urine from Mexican population. A cross-sectional, comparative, and clinical study with translational approach was performed. We recruited twenty T2D patients and twenty-one healthy subjects. Urine samples were taken and analyzed by FGC eNose. Eighty-eight compounds were identified through Kovats's indexes. A natural variation of 30% between the metabolites, expressed by study groups, was observed in Principal Component 1 and 2 with a significant difference (p < 0.001). The model, performed through a Canonical Analysis of Principal coordinated (CAP), allowed a correct classification of 84.6% between healthy and T2D patients, with a 15.4% error. The metabolites 2-propenal, 2-propanol, butane- 2,3-dione and 2-methylpropanal, were increased in patients with T2D, and they were strongly correlated with discrimination between clinically healthy people and T2D patients. This study identified metabolites in urine through FGC eNose that can be used as biomarkers in the identification of T2D patients. However, more studies are needed for its implementation in clinical practice.

Prevalence of diabetic nephropathy in Type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment.

OBJECTIVE: To determine the prevalence of Diabetic Nephropathy (DN) in patients with type 2 Diabetes Mellitus (T2DM) with over 5 years of evolution in rural communities of Guanajuato, Mexico, and evaluate the effects of an ARB treatment over 6 months in patients with DN. MATERIALS AND METHODS: Patients of both sexes, 38-86 years, T2DM over 5 years of evolution and diagnosed with arterial hypertension (HT) after T2DM incidence. Monthly determination of microalbuminuria (MA), lipids, glucose, serum creatinine, and glycated hemoglobin (HbA1c). Estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. A dose of 80 mg of Telmisartan was administered daily over 6 months. RESULTS: The total adult population of two rural communities (3609 subjects) was studied, 335 subjects had T2DM, among them 80 (with a prevalence of 24%) had DN and HT. Sixty-seven patients received Telmisartan, and showed significant improvement in all parameters studied. CONCLUSIONS: A higher prevalence of DN than that reported in the Mexican National Health Survey (ENSANUT) was found. Further research is required in a larger population sample in order to confirm the results of Telmisartan treatment.

Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients.

AIMS: Antioxidant selenium (Se) properties and, its protective role against oxidative damage play an important role in diabetic complications. Our objective was to gain further insight on a link between selenium status and diabetic nephropathy. METHODS: We assessed glutathione peroxidase (GPx) and Se in type 2 diabetes mellitus patients with microalbuminuria (MA) (group 1), without microalbuminuria (group 2), and in control subjects (group 3). Glucose, urea, creatinine and glycated hemoglobin tests were tested in sera. A complete clinical record was elaborated. RESULTS: For diabetic patients both, the time from diagnosis and plasma glucose concentration were higher in group 1 as compared to group 2. Control group showed higher serum Se concentrations as compared to the diabetic groups. The two groups of diabetic patients showed similar serum Se levels. Serum concentration of GPx was significantly lower in group 1 as compared to groups 2 and 3. Microalbuminuria (MA) test showed a positive correlation with glucose, and a negative relationship with serum Se and GPx. Multiple regression revealed an inverse relationship between selenium or GPx in serum and the results of the MA test. CONCLUSIONS: Our results suggest that lower Se and GPx levels in diabetic patients may be implicated in the diabetic nephropathy.

Occupational exposure to toluene and its possible causative role in renal damage development in shoe workers.

OBJECTIVES: An important, although, unprecise number of shoe workers in Leon, Mexico, are in continuous contact with toluene-based glues. The induction of renal glomerular and/or tubular lesions as a result of toluene exposure is still being discussed controversially. Our objective was to evaluate the extent of occupational exposure, assessing urinary o-Cresol excretion as a measure for toluene exposure in a population at risk as compared to a control population. Urinary albumin excretion (UAE) and N-acetyl-beta-D-glucosaminidase (NAG) enzymatic activity were tested to assess renal dysfunction. METHODS: A cross-sectional study was performed comparing 50 toluene-exposed shoe workers and 25 control subjects. Urinary o-cresol was assessed on first and last day of labor week from exposed subjects. A single urine sample was obtained from control subjects. Urinary Albumin excretion (UAE) and (NAG) activity were examined in 12 h urine samples in all subjects. Urine and serum creatinine were measured to asses renal function. RESULTS: At the end of the labor week, urinary o-cresol levels were higher in samples obtained from exposed subjects. Albumin excretion was similar in the exposed and control groups. NAG activity was greater in the exposed group compared to control group (median 3.5 U/g creatinine vs 1.9 U/g creatinine, z=2.6, P=0.009). An inverse relationship was found between schooling years and the NAG enzymatic activity for the two studied groups (r= -0.27, P=0.02), CONCLUSIONS: Our findings support the hypothesis that toluene may be a factor associated with the presence of renal damage in exposed shoe workers. As NAG activity is increased, we believe the lesion initiates in the renal tubular cells.

Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure.

Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFalpha) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFalpha in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFalpha were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFalpha concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF.

Dosis semanal única de eritropoyetina recombinante en niños con insuficiencia renal crónica / Recombinant human erhytropoietin once a week in the treatment of anemia in children whit end stage renal failure

Objetivo: Estudiar el resultado de la aplicación de una dosis semanal de eritropoyetina humana recombinante (EPO) por vía subcutánea en el tratamiento de la anemia de niños con insuficiencia renal terminal (IRT). Diseño. Se estudiaron 19 pacientes de 6 a 17 años de edad con IRT del programa de dialisis peritoneal crónica ambulatoria (DPCA) del Centro Médico Nacional de la ciudad de León. Los enfermos habían requerido previamente un promedio 2.8 transfusiones sanguíneas en 18.2 meses. Los requisitos de inclusión fueron: anemia normocrómica severa (Hto > 20 por ciento), ausencia de procesos infecciosos y otras enfermedades sistémicas, cifras tensionales por debajo de la percential 97 para su edad, función hepática normal, y ausencia de crisis convulsivas. La EPO se administró por vía subcutánea una vez por semana a razón de 130 ñ (DE) 15 U/kg de peso. Todos los pacientes recibieron diariamente los requerimientos mínimos de sulfato ferroso y ácido fólico. Resultados. Los valores iniciales promedio fueron de 6.6 ñ 0.9 g/dL y 20.6 ñ 3.3 por ciento para la hemoglobina y el hematocrito respectivamente, elevándose a 9.4 ñ 0.9 g/dL y 28.8 ñ 2.5 por ciento a las doce semanas (p< 0.05). Los pacientes no recibieron hemotransfusiones durante el periodo de estudio. La presión arterial no mostró cambios significativos. Conclusiones. La administración subcutánea de EPO en nuestro estudio fue suficiente para obtener un aumento en los valores de Hb y Hto en los pacientes estudiados. Adicionalmente se obtuvo una disminución en la aparición de efectos secundarios y en el costo del tratamiento