TY - JOUR
T1 - Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Nondiabetic Patients on Hemodialysis Using Metabolomic Profiling
AU - Chen, Wei
AU - Fitzpatrick, Jessica
AU - Sozio, Stephen M.
AU - Jaar, Bernard G.
AU - Estrella, Michelle M.
AU - Riascos-Bernal, Dario F.
AU - Wu, Tong Tong
AU - Qiu, Yunping
AU - Kurland, Irwin J.
AU - Dubin, Ruth F.
AU - Chen, Yabing
AU - Parekh, Rulan S.
AU - Bushinsky, David A.
AU - Sibinga, Nicholas E.S.
N1 - Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Background A better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC. Methods In this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (n51), and controls were patients without diabetes with a CAC score of zero (n48). We measured 452 serum metabolites in each participant. Metabolites and pathway scores were compared using Mann-Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses. Results Compared with controls, cases were older (64±13 versus 42±12 years) and were less likely to be Black (51% versus 94%). We identified three metabolites in bile-acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one pathway (arginine/proline metabolism). After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC; comparing the third with the first tertile of each bile acid, the OR was 6.34 (95% CI, 1.12 to 36.06), 6.73 (95% CI, 1.20 to 37.82), and 8.53 (95% CI, 1.50 to 48.49), respectively. These associations were no longer significant after further adjustment for coronary artery disease and medication use. Per 1 unit higher in the first principal component score, arginine/proline metabolism was associated with CAC after adjusting for demographics (OR, 1.83; 95% CI, 1.06 to 3.15), and the association remained significant with additional adjustments for statin use (OR, 1.84; 95% CI, 1.04 to 3.27). Conclusions Among patients on HD without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism is a plausible mechanism to study for CAC. These findings need to be confirmed in future studies.
AB - Background A better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC. Methods In this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (n51), and controls were patients without diabetes with a CAC score of zero (n48). We measured 452 serum metabolites in each participant. Metabolites and pathway scores were compared using Mann-Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses. Results Compared with controls, cases were older (64±13 versus 42±12 years) and were less likely to be Black (51% versus 94%). We identified three metabolites in bile-acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one pathway (arginine/proline metabolism). After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC; comparing the third with the first tertile of each bile acid, the OR was 6.34 (95% CI, 1.12 to 36.06), 6.73 (95% CI, 1.20 to 37.82), and 8.53 (95% CI, 1.50 to 48.49), respectively. These associations were no longer significant after further adjustment for coronary artery disease and medication use. Per 1 unit higher in the first principal component score, arginine/proline metabolism was associated with CAC after adjusting for demographics (OR, 1.83; 95% CI, 1.06 to 3.15), and the association remained significant with additional adjustments for statin use (OR, 1.84; 95% CI, 1.04 to 3.27). Conclusions Among patients on HD without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism is a plausible mechanism to study for CAC. These findings need to be confirmed in future studies.
KW - arginine and proline metabolism
KW - arterial calcification
KW - bile acid
KW - coronary artery disease
KW - dialysis
KW - metabolomics
KW - mineral metabolism
UR - http://www.scopus.com/inward/record.url?scp=85148021940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85148021940&partnerID=8YFLogxK
U2 - 10.34067/KID.0004422020
DO - 10.34067/KID.0004422020
M3 - Article
AN - SCOPUS:85148021940
SN - 2641-7650
VL - 2
SP - 279
EP - 289
JO - Kidney360
JF - Kidney360
IS - 2
ER -