Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha-ketoisovaleric acid, valine, isobutyrate, D-Palmitylcarnitine, histidine, and N-methylnicotinamide. Pathway analysis revealed impairment of the branched-chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.
Objective: Non-alcoholic fatty liver disease (NAFLD) is as silent comorbidity in many different settings including; diabetes mellitus (DM), obesity, and hyperlipidemia. In this study, we aimed to determine the incidence of NAFLD in referral outpatients to the internal medicine clinic to evaluate correlations between NAFLD in the other clinical backgrounds. Materials and Methods: We performed a cross-sectional study on 88 consecutive referral patients to the internal medicine clinic. Patients with a history of liver disease and alcohol consumption were excluded. Liver ultrasound was performed for diagnosing of NAFLD to be mild to moderate (Grade 1), or moderate to a severe degree of involvement (Grade 2). Clinical backgrounds of the patients, including history and laboratory exam tests such as age, exercise, and DM as well as lipid profile, and liver enzyme test results investigated in our study. Results: The incidence of NAFLD was 62% (40% Grade 2; 60% Grade 1). Patients with NAFLD had a higher body mass index, (30 ± 5 vs. 27 ± 4; P = 0.04). They were younger than patients who had not NAFLD (46 ± 15 vs. 58 ± 10 years; P = 0.0001). Total cholesterol level was higher in patients with NAFLD (198 ± 46 vs. 175 ± 46 mg/Dl; P = 0.03). Patients with NAFLD had higher serum alanine aminotransferase (ALT) level (50 ± 14 vs. 46 ± 15 IU/l; P = 0.0001). The aspartate aminotransferase/ALT ratio was lower in patients with NAFLD (0.8 ± 0.3 vs. 1 ± 0.2; P = 0.0001). Patients with NAFLD had sedentary lifestyle compared to those with normal liver (P = 0.001). Conclusion: More than half of the referral outpatients to the internal medicine clinic have NAFLD. It occurs in the young age population of patients and has a strong correlation with high-cholesterol level and sedentary lifestyle.
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