Additional file 1: of Frequency of arrhythmia symptoms and acceptability of implantable cardiac monitors in Hemodialysis patients

Study Questionnaire: Appendix. Study Questionnaire. (PDF 157 kb

Additional file 1: Figure S1. of Cross-sectional association of volume, blood pressures, and aortic stiffness with left ventricular mass in incident hemodialysis patients: the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) study

Boxplot of left ventricular mass index (LVMI) and quartiles of systolic or diastolic blood pressures measured as predialysis 3-month average BP measurement stratified by ethnicity. Figure S2: Boxplot of left ventricular mass index (LVMI) and quartiles of systolic or diastolic blood pressures measured as prior to clinic BP measurement stratified by ethnicity. Figure S3: Boxplot of left ventricular mass index (LVMI) and quartiles of systolic or diastolic blood pressures measured as non-dialysis supine BP measurement stratified by ethnicity. Table S1: Independent associations of predialysis blood pressure, arterial, and volume measures with LVMI by linear regression among incident hemodialysis participants. Table S2: Independent associations of blood pressure prior to study visit, arterial, and volume measures withLVMI by linear regression among incident hemodialysis participants. Table S3: Independent associations of mean arterial pressure, arterial, and volume measures with LVMI by linear regression among incident hemodialysis participants. Table S4: Independent associations of pulse pressures, arterial, and volume measures with LVMI by linear regression among incident hemodialysis participants. Table S5: Association of preload and afterload measures with LVMI by linear regression among incident hemodialysis participants stratified by ethnicity. Table S6: Association of preload and afterload measures with LVMI by linear regression among incidenthemodialysis participants stratified by 3 month average IDWG groups. Table S7: Association of preload and afterload measures with LVMI by linear regression among incident hemodialysis participants stratified by β-blocker medication. Table S8: Association of preload and afterload measures with LVMI by linear regression among incident hemodialysis participants stratified by renin-angiotensin-aldosterone system (RAAS) blockade use. Table S9: Association of preload and afterload measures with LVMI by linear regression among incident hemodialysis participants stratified by history of congestive heart failure. Table S10: Association of hemoglobin with LVMI by linear regression among incident hemodialysis participants. (DOCX 97 kb

Biological and technical variability of SomaScan.

Short-term biological and intra-assay CVs for 4802 proteins are shown in 4 study participants who had samples available for both types of CVs from the CERES cohort.</p

Orthogonal correlations for aptamer and traditional assays in CERES participants.

Spearman rho correlations were analyzed for aptamer and traditional assays. Aptamer measures were analyzed in three data formats: raw data, median normalized, and ANML. X-axes show the aptamer measure in relative fluorescence units (RFU), and the y-axes show the traditional assay. CRP: c-reactive protein. FGF23: fibroblast growth factor 23. NT-proBNP: N-terminal pro-B-type natriuretic peptide. PTH: parathyroid hormone.</p

Proteins meeting significance criteria for fold change in CERES participants who died, using three normalization formats.

Proteins meeting significance criteria for fold change in CERES participants who died, using three normalization formats.</p

SomaScan technical information.

BackgroundPatients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure.MethodsForty participants from the Cardiac, Endothelial Function and Arterial Stiffness in End-Stage Renal Disease (CERES study) were selected to analyze technical and short-term biological variability, orthogonal correlations and differential protein expression in plasma from patients who died during 2.5 year follow-up. Long-term (one year) variability was studied in 421 participants in the Chronic Renal Insufficiency Cohort. We evaluated 4849 aptamers (4607 unique proteins) using data formats including raw data and data formatted using Adaptive Normalization by Maximum Likelihood (ANML), an algorithm developed for SomaScan data in individuals with normal kidney function.ResultsIn ANML format, median[IQR] intra-assay coefficient of variation (CV) was 2.38%[1.76, 3.40] and inter-assay CV was 7.38%[4.61, 13.12]. Short-term within-subject CV was 5.76% [3.35, 9.72]; long-term CV was 8.71%[5.91, 13.37]. Spearman correlations between aptamer and traditional assays for PTH, NT-proBNP, FGF-23 and CRP were all > 0.7. Fold-change (FC) in protein levels among non-survivors, significant after Bonferroni correction, included SVEP1 (FC[95% CI] 2.14 [1.62, 2.82]), keratocan (1.74 [1.40, 2.15]) and LanC-like protein 1 (0.56 [0.45, 0.70]). Compared to raw aptamer data, technical and short-term biological variability in paired samples was lower in ANML-formatted data. ANML formatting had minimal impact on orthogonal correlations with traditional assays or the associations of proteins with the phenotype of mortality.ConclusionsSomaScan had excellent technical variability and low within-subject short-term variability. ANML formatting could facilitate comparison of biomarker results with other studies that utilize this format. We expect SomaScan to provide novel and reproducible information in patients with kidney failure on dialysis.</div

S2 File -

S2 Table 1 Proteins Excluded From Variability Analyses. S2 Table 2 Baseline Characteristics of CRIC Participants with Kidney Failure on Hemodialysis. S2 Table 3 Proteins with Intra-assay CV>20% Using Raw or ANML Data Format. S2 Table 4 Proteins with Inter-assay CV>40% Using Raw or ANML Data Format. S2 Table 5 Short-term Biological Variability Measured Separately in 4 CERES Participants. S2 Table 6 Long-term Variablity of Proteins in 421 CRIC Participants: Raw Data Format. S2 Table 7 Long-term Variablity of Proteins in 421 CRIC Participants: ANML Data Format. S2 Table 8 Correlations of Fold Change and P-values of Proteins in Non-survivors. S2 Table 9 Fold Change (FC) in Protein Level in Non-Survivors Compared to Survivors Using Raw Data. S2 Table 10 Fold Change (FC) in Protein Level in Non-Survivors Compared to Survivors Using Median Normalized Data. (ZIP)</p

Technical and biological variability of somascan in plasma samples of patients with kidney failure.

Coefficient of variation (CV) and spearman rho correlations between pairs of samples are shown above. Data are from CERES study with the exception of long-term within-subject variability, calculated from CRIC data.</p

Fold Change (FC) in protein levels among non-survivors compared to survivors in 40 CERES participants.

Fold Change (FC) in protein levels among non-survivors compared to survivors in 40 CERES participants.</p

Baseline characteristics of 40 participants with kidney failure.

Baseline characteristics of 40 participants with kidney failure.</p