Renal function at entry and follow-up stratified by gender.

<p>Renal function at entry and follow-up stratified by gender.</p

Patient demographics.

<p>Results indicate mean values unless otherwise indicated.</p><p>Parentheses indicate 95% confidence intervals.</p>*<p>indicates a statistically significant association with gender (p value<0.05).</p

Estimated glomerular filtration rate in patients at follow-up.

<p>Abbreviation: GFR, glomerular filtration rate.</p><p>Results indicate percentage.</p><p>Percentages indicate 95% confidence interval.</p>*<p>indicates a statistically significant association with gender (p value<0.05).</p

Creatinine in patients at entry.

<p>Results indicate percentages.</p><p>Parentheses indicate 95% confidence intervals.</p>*<p>indicates a statistically significant association with gender (p value<0.05).</p

Demographics of study subjects according to FMO3 p.158E>K genetic variant.

<p>Demographics of study subjects according to FMO3 p.158E>K genetic variant.</p

Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients

<div><p>Elevated levels of circulating pro-atherogenic uremic solutes, particularly trimethylamine N-oxide (TMAO), have been implicated in cardiovascular disease development in patients with chronic kidney disease (CKD). TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). We determined the functional effects of three common FMO3 variants at amino acids 158, 308, and 257 on TMAO concentrations in a prospective cohort study and evaluated associations of polymorphisms with CKD progression and mortality. Each additional minor allele at amino acid 158 was associated with a 0.38 μg/mL higher circulating TMAO (p = 0.01) and with faster rates of annualized relative eGFR decline. Participants with 0, 1 and 2 variant alleles averaged an eGFR loss of 8%, 12%, and 14% per year, respectively (p-for trend = 0.05). Compared to participants with the homozygous reference allele, heterozygous and homozygous variant participants had a 2.0-fold (95% CI: 0.85, 4.6) and 2.2-fold (95% CI: 0.89, 5.48) higher risk of mortality, respectively (p-for-trend = 0.04). No associations with clinical outcomes were observed for allelic variants at amino acids 257 or 308. Understanding the contribution of genetic variation of FMO3 to disease progression and all-cause mortality can guide recommendations for diet modification or pharmacotherapy in CKD patients at increased risk of adverse outcomes.</p></div

Scatterplot of plasma TMAO concentration versus estimated GFR for subjects with FMO3 E/E (open square) and FMO3 E/K or K/K (closed circle) allelic variants.

<p>TMAO concentration increases as eGFR decreases, with greater rate of increase observed with eGFR < 40 mL/min/1.73m². Dashed line indicates the Lowess curve for reference allele homozygous subjects (158 E/E). Dotted line indicates the Lowess curve for heterozygous or variant homozygous subjects (158 E/K or K/K).</p

FMO3 allelic variants vs plasma TMAO concentration.

<p>FMO3 allelic variants vs plasma TMAO concentration.</p

Association of Genotype and Kidney Disease Progression and all-cause mortality.

<p>Association of Genotype and Kidney Disease Progression and all-cause mortality.</p

Additional file 1: of Association of markers of endothelial dysregulation Ang1 and Ang2 with acute kidney injury in critically ill patients

Pairwise correlation matrix of endothelial and inflammatory biomarkers. Pearson’s correlation coefficient (ρ) was used to estimate the magnitude of the linear correlation between log-transformed biomarker concentrations. (DOCX 15 kb