Associations of metabolites with subsequent renal function decline. A: Global matrix of correlation coefficients of all commonly detected amino acids and nucleotides (n = 114) with baseline eGFR (x-axis) and with a subsequent eGFR slope (y-axis). Each mark represents a correlation coefficient of an individual metabolite. Modified metabolites are represented as open shapes (blue □, C-glycosylated; red △, sulfated; orange ○, acylated; green ◇, carbamylated; purple bars, methylated). All the remaining metabolites are presented as ●. B: Score plot of PC1 and PC2 based on nine significant candidate metabolites identified in the global matrix analysis. Marks represent individual study participants with renal function decline in the bottom tertile of the eGFR slope distribution (decliners) and those in the top tertile of the eGFR slope distribution (nondecliners). The labels of the x- and y-axes include the explained variance. CGST, C-glycosyltryptophan; CRE, creatinine; N6CA, N6-carbamoylthreonyladenosine; NATHR, N-acetylthreonine; OST, O-sulfotyrosine; PSD, pseudouridine.
Nine modified metabolites significant in the global multivariate analysis as candidate biomarkers for progression to ESRD. Reproducibility over time is expressed as ICCs. HRs are presented per 1 SD of the metabolite. Partially adjusted HRs are controlled for baseline HbA1c, ACR, and eGFR. Fully adjusted HRs are controlled for blood pressure, BMI, smoking status, HbA1c, ACR, eGFR, uric acid levels, treatment with renin-angiotensin system inhibitors, other antihypertensive treatment, and statins.
Matrix of correlation coefficients among and between modified metabolites and baseline indices of diabetic kidney injury: glycemic control (HbA1c), glomerular markers (ACR, IgG2), and tubular markers (KIM-1, NGAL). Cell color indicates strengths and directions of the correlations from red (positive correlation) to white (no correlation) to blue (negative correlation).