





Item type: | Article | ||||||
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Journal or Publication Title: | American Journal of Kidney Diseases | ||||||
Publisher: | W B SAUNDERS CO-ELSEVIER INC | ||||||
Place of Publication: | PHILADELPHIA | ||||||
Date: | 9 April 2021 | ||||||
Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) | ||||||
Identification Number: |
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Keywords: | DISEASE GCKD; ALL-CAUSE; RISK; TRYPTOPHAN; HAZARDS; DESIGN; | ||||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||
Status: | Published | ||||||
Refereed: | Yes, this version has been refereed | ||||||
Created at the University of Regensburg: | Partially | ||||||
Item ID: | 47759 |
Abstract
Rationale & Objective: Mechanisms underlying the variable course of disease progression in patients with chronic kidney disease (CKD) are incompletely understood. The aim of this study was to identify novel biomarkers of adverse kidney outcomes and overall mortality, which may offer insights into pathophysiologic mechanisms. Study Design: Metabolome-wide association study. Setting & Participants: ...

Abstract
Rationale & Objective: Mechanisms underlying the variable course of disease progression in patients with chronic kidney disease (CKD) are incompletely understood. The aim of this study was to identify novel biomarkers of adverse kidney outcomes and overall mortality, which may offer insights into pathophysiologic mechanisms. Study Design: Metabolome-wide association study. Setting & Participants: 5,087 patients with CKD enrolled in the observational German Chronic Kidney Disease Study. Exposures: Measurements of 1,487 metabolites in urine. Outcomes: End points of interest were time to kidney failure (KF), a combined end point of KF and acute kidney injury (KF+AKI), and overall mortality. Analytical Approach: Statistical analysis was based on a discovery-replication design (ratio 2:1) and multivariable-adjusted Cox regression models. Results: After a median follow-up of 4 years, 362 patients died, 241 experienced KF, and 382 experienced KF+AKI. Overall, we identified 55 urine metabolites whose levels were significantly associated with adverse kidney outcomes and/or mortality. Higher levels of C-glycosyltryptophan were consistently associated with all 3 main end points (hazard ratios of 1.43 [95% CI, 1.27-1.61] for KF, 1.40 [95% CI, 1.27-1.55] for KF+AKI, and 1.47 [95% CI, 1.33-1.63] for death). Metabolites belonging to the phosphatidylcholine pathway showed significant enrichment. Members of this pathway contributed to the improvement of the prediction performance for KF observed when multiple metabolites were added to the well-established Kidney Failure Risk Equation. Limitations: Findings among patients of European ancestry with CKD may not be generalizable to the general population. Conclusions: Our comprehensive screen of the association between urine metabolite levels and adverse kidney outcomes and mortality identifies metabolites that predict KF and represents a valuable resource for future studies of biomarkers of CKD progression.
Metadata last modified: 29 Sep 2021 07:42