Plosone.orgHeritability of Uremic Retention MoleculesFigure 2. Indoxyl sulfate and p-cresyl sulfate according to age. The dots indicate the geometric means of indoxyl sulfate (IndS) and p-cresyl sulfate (PCS) in decades of age (,30 years, 30?9 years, 40?9 years, 50?9 years, 60?9 years and 70 years). The numbers above the horizontal axis will be the number of subjects in the several age classes. The curves are calculated from a regression model with log IndS and log PCS as dependent variables and age and age-squared as independent variables. For IndS the P-values in the linear and squared terms had been 0.035 and 0.0024 respectively. The corresponding P-values for PCS have been 0.070 and 0.004. doi:ten.1371/journal.pone.0079682.gRegression evaluation identified renal function, age and sex as independent determinants of serum levels of both co-metabolites. The dependence from the serum concentrations of indoxyl sulfate and p-cresyl sulfate on renal function is ETA Antagonist review anticipated as each co-metabolites are well-known uremic retention molecules [31]. Additionally, recent proof indicates that uremia per se could profoundly alter the composition with the gut microbiome [32]. In line using the latter, we observed improved generation of p-cresyl sulfate along the progression of chronic kidney illness [33]. The association between the serum concentrations of indoxyl sulfate and p-cresyl sulfate and age is exceptional and intriguingand confirms prior observations in chronic kidney disease individuals [23]. These observations support the hypothesis that aging goes in addition to a trend towards the Bacteroides enterotype and thus extra prominent proteolytic fermentation and essentially concur with information from previous “classical” microbiology research [34,35]. Whether or not these modifications are related to a reduced immune function or no matter if they are as a consequence of concomitant adjustments in nutrition, gastrointestinal tract physiology, comorbidity and use of medication with advancing age remains to be established.Table 1. Baseline characteristics by quartiles of indoxyl sulfate.Indoxyl Sulfate, mmol/L Traits Characteristic n ( ) Males Hypertension Antihypertensive drug intake Diabetes mellitus Current smokers Present drinkers History of CV illness Age-adjusted traits Body mass index, kg/m2 Systolic blood pressure, mmHg Diastolic blood stress, mmHg Serum cholesterol, mmol/L Triglycerides, mmol/L Serum creatinine, mmol/L Measured creatinine clearance, ml/sec/1.73m,2.39 (n = 197)two.39?.149 (n = 192)3.150?.275 (n = 192).4.275 (n = 192)P100 (50.8) 67 (33.8) 33 (16.8) 4 (two.0) 55 (27.9) 156 (79.2) 14 (7.1)86 (44.8) 77 (40.1) 43 (22.4) six (three.1) 44 (22.9) 127 (66.1) 18 (9.four)88 (45.8) 77 (40.1) 51 (26.six) 5 (two.6) 32 (16.7) 118 (61.5) 16 (8.three)110 (57.three) 97 (50.1) 68 (35.4) 12 (6.3) 26 (13.five) 132 (68.8) 24 (12.5)0.206 0.01 ,0.0001 0.044 0.0002 0.014 0.26.two(0.30) 129.7(1.04) 80.1(0.64) 5.2(0.066) 1.7(0.076) 82.four(1.11) 1.7(0.041) 93.6(1.63)26.five(0.31) 127.7(1.04) 78.9(0.65) five.two(0.066) 1.eight(076) 81.6(1.11) 1.7(0.041) 94.9(1.64)26.6(0.30) 128.4(1.04) 79.6(0.65) 5.2(0.066) 1.eight(076) 82.eight(1.11) 1.eight(0.041) 94.five(1.64)26.8(0.31) 132.0(1.05) 81.1(0.65) 5.4(0.067) two.two(077) 90.three(1.12) 1.7(0.041) 90.9(1.65)0.507 0.023 0.104 0.170 ,0.0001 ,0.0001 0.852 0.Calculated creatinine clearance, ml/min/1.73mP-value for trend across the quartiles is provided. Values are imply (SD) or Bcl-xL Inhibitor MedChemExpress quantity of participants ( ) as acceptable. doi:10.1371/journal.pone.0079682.tPLOS 1 | plosone.orgHeritability of Uremic Retention MoleculesTable two. B.
