Additional file 1: of Patient and treatment characteristics associated with patient activation in patients undergoing hemodialysis: a cross-sectional study

Questionnaire used in the study. The survey questioned demographic, social and illness-related information. Moreover, the questionnaire on patient activation was also included. The participants have completed the Dutch translation of this questionnaire. (DOC 331 kb

Heritability and Clinical Determinants of Serum Indoxyl Sulfate and <i>p</i>-Cresyl Sulfate, Candidate Biomarkers of the Human Microbiome Enterotype

<div><p>Background</p><p>Indoxyl sulfate and <i>p</i>-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and <i>p</i>-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden.</p><p>Objective and Design</p><p>Information on clinical determinants and heritability of indoxyl sulfate and <i>p</i>-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and <i>p</i>-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study).</p><p>Results</p><p>Serum levels of indoxyl sulfate and <i>p</i>-cresyl sulfate amounted to 3.1 (2.4–4.3) and 13.0 (7.4–21.5) μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h² = 0.17) and <i>p</i>-cresyl sulfate (h² = 0.18) concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites.</p><p>Limitations</p><p>Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded.</p><p>Conclusions</p><p>The heritability of indoxyl sulfate and <i>p</i>-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.</p></div

Distribution of indoxyl sulfate and <i>p</i>-cresyl sulfate.

<p>The vertical line is the limit of quantification.</p

Baseline characteristics by quartiles of <i>p</i>-cresyl sulfate.

<p>The P-value for trend across the quartiles is given. Values are mean±SD or number of participants (%) as appropriate.</p

Heritability of indoxyl sulfate and <i>p</i>-cresyl sulfate.

<p>Values are proportions ± standard error. Indoxyl sulfate and <i>p</i>-cresyl sulfate were log-transformed.</p><p>h², heritability.</p><p>Adjusted for sex, age (linear and squared term), triglycerides, current smoking status, measured creatinine clearance and history of cardiovascular complications.</p

Determinants of indoxyl sulfate and <i>p</i>-cresyl sulfate.

<p>^*P<0.05; ^**P<0.01; ^***P<0.001; P<0.0001.</p><p>First a stepwise regression model not taking into account family relationships was used to select the covariables. Then, a mixed model with family included as a random effect and the covariables selected in the previous step entered as fixed effects was used to calculate parameter estimates. The following variables were offered to the stepwise regression model: sex, age (linear and squared term), systolic and diastolic blood pressure, history of cardiovascular disease, antihypertensive drug intake, current smoking and alcohol intake, body mass index, diabetes mellitus, serum total cholesterol, triglycerides, serum creatinine and calculated creatinine clearance.</p

Baseline characteristics by quartiles of indoxyl sulfate.

<p>P-value for trend across the quartiles is given. Values are mean (SD) or number of participants (%) as appropriate.</p

Indoxyl sulfate and <i>p</i>-cresyl sulfate according to age.

<p>The dots indicate the geometric means of indoxyl sulfate (IndS) and p-cresyl sulfate (PCS) in decades of age (<30 years, 30–39 years, 40–49 years, 50–59 years, 60–69 years and ≥70 years). The numbers above the horizontal axis are the number of subjects in the various 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 of the linear and squared terms were 0.035 and 0.0024 respectively. The corresponding P-values for PCS were 0.070 and 0.004.</p

Tissue hydration related to percentiles of the normal reference population stratified for the use of polyglucose or not.

<p>Tissue hydration related to percentiles of the normal reference population stratified for the use of polyglucose or not.</p

Demographic, clinical and fluid status data of the EuroBCM study cohort (N = 639).

§<p>after exclusion of patients from countries where polyglucose and APD are not liberally available due to logistical reasons.</p