Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans.

Background: MicroRNAs (miRNAs) are noncodingRNAmolecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have distinct circulating and urinary miRNAexpression profiles that could lead to potential development of noninvasive biomarkers of the disease.Materials and methods: Exosome miRNAs were extracted from plasma and urine samples of patients with primaryFSGS(n = 16) orMCD(n = 5) and healthy controls (n = 5). Differences in miRNAabundance were examined using Affymetrix GeneChip miRNA3.0 arrays.QRT‐PCRwas used to validate the findings from the array.Results: Comparison analysis ofFSGSversusMCDrevealed 126 and 155 differentially expressed miRNAs in plasma and in urine, respectively. Only 38 of these miRNAs were previously cited, whereas the remaining miRNAs have not been described. Comparison analysis showed that a significant number of miRNAs were downregulated in both plasma and urine samples of patients withFSGScompared to those withMCD. Plasma levels of miR‐30b, miR‐30c, miR‐34b, miR‐34c and miR‐342 and urine levels of mir‐1225‐5p were upregulated in patients withMCDcompared to patients withFSGSand controls (P < 0·001). Urinary levels of mir‐1915 and miR‐663 were downregulated in patients withFSGScompared toMCDand controls (P < 0·001), whereas the urinary levels of miR‐155 were upregulated in patients withFSGSwhen compared to patients withMCDand controls (P < 0·005).Conclusions: Patients withFSGSandMCDhave a unique circulating and urinary miRNAprofile. The diagnostic and prognostic potential of miRNAs inFSGSandMCDwarrants further studies.