Plosone.orgHeritability of Uremic Retention MoleculesFigure 2. Indoxyl sulfate and p-cresyl sulfate as outlined by 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 are the quantity of subjects in the various age classes. The curves are DKK-1 Protein custom synthesis 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 from the linear and squared terms were 0.035 and 0.0024 respectively. The corresponding P-values for PCS were 0.070 and 0.004. doi:10.1371/journal.pone.0079682.gRegression evaluation identified renal function, age and sex as independent determinants of serum levels of both co-metabolites. The dependence on the serum concentrations of indoxyl sulfate and p-cresyl sulfate on renal function is anticipated as both co-metabolites are well-known uremic retention molecules [31]. Moreover, recent evidence indicates that uremia per se may profoundly alter the composition in the gut microbiome [32]. In line with all the latter, we observed increased generation of p-cresyl sulfate along the progression of chronic kidney disease [33]. The association involving the serum concentrations of indoxyl sulfate and p-cresyl sulfate and age is exceptional and intriguingand confirms prior observations in chronic kidney illness sufferers [23]. These observations assistance the hypothesis that aging goes in conjunction with a trend towards the Bacteroides enterotype and therefore extra prominent proteolytic fermentation and essentially concur with data from previous “classical” microbiology studies [34,35]. Whether these modifications are related to a lowered immune function or regardless of whether they may be resulting from concomitant adjustments in nutrition, gastrointestinal tract physiology, comorbidity and use of medication with advancing age remains to become established.Table 1. Baseline characteristics by TDGF1 Protein supplier quartiles of indoxyl sulfate.Indoxyl Sulfate, mmol/L Characteristics Characteristic n ( ) Guys Hypertension Antihypertensive drug intake Diabetes mellitus Existing smokers Existing drinkers History of CV disease Age-adjusted characteristics Physique mass index, kg/m2 Systolic blood stress, mmHg Diastolic blood pressure, mmHg Serum cholesterol, mmol/L Triglycerides, mmol/L Serum creatinine, mmol/L Measured creatinine clearance, ml/sec/1.73m,two.39 (n = 197)two.39?.149 (n = 192)3.150?.275 (n = 192).four.275 (n = 192)P100 (50.eight) 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 (3.1) 44 (22.9) 127 (66.1) 18 (9.4)88 (45.8) 77 (40.1) 51 (26.6) five (2.six) 32 (16.7) 118 (61.5) 16 (eight.three)110 (57.three) 97 (50.1) 68 (35.4) 12 (six.three) 26 (13.5) 132 (68.eight) 24 (12.five)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) five.2(0.066) 1.7(0.076) 82.4(1.11) 1.7(0.041) 93.six(1.63)26.five(0.31) 127.7(1.04) 78.9(0.65) 5.2(0.066) 1.8(076) 81.6(1.11) 1.7(0.041) 94.9(1.64)26.6(0.30) 128.4(1.04) 79.six(0.65) five.2(0.066) 1.8(076) 82.eight(1.11) 1.eight(0.041) 94.5(1.64)26.eight(0.31) 132.0(1.05) 81.1(0.65) 5.4(0.067) 2.2(077) 90.3(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 offered. Values are mean (SD) or number of participants ( ) as appropriate. doi:10.1371/journal.pone.0079682.tPLOS 1 | plosone.orgHeritability of Uremic Retention MoleculesTable two. B.
