Steinbrenner, Inga and Schultheiss, Ulla T. and Baechle, Helena and Cheng, Yurong and Behning, Charlotte and Schmid, Matthias and Yeo, Wan-Jin and Yu, Bing and Grams, Morgan E. and Schlosser, Pascal and Stockmann, Helena and Gronwald, Wolfram and Oefner, Peter J. and Schaeffner, Elke and Eckardt, Kai-Uwe and Koettgen, Anna and Sekula, Peggy (2024) Associations of Urine and Plasma Metabolites With Kidney Failure and Death in a Chronic Kidney Disease Cohort. AMERICAN JOURNAL OF KIDNEY DISEASES, 84 (4). pp. 469-481. ISSN 0272-6386, 1523-6838
Full text not available from this repository. (Request a copy)Abstract
Rationale & Objective: Biomarkers that enable better identification fi cation of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease. Study Design: Prospective metabolome-wide association study. Setting & Participants: Persons with CKD enrolled in the GCKD (German CKD) study with metabolite measurements, with external validation within the ARIC (Atherosclerosis Risk in Communities) Study. Exposures: 1,513 urine and 1,416 plasma metabolites (Metabolon Inc) measured at study entry using untargeted mass spectrometry. Outcomes: Main end points were kidney failure (KF) and a composite kidney end point (CKE) of KF, estimated glomerular fi ltration rate < 15 mL/min/ 1.73 m(2), or a 40% decrease in estimated glomerular fi ltration rate. Death from any cause was a secondary end point. After a median of 6.5 years of follow-up, 500 persons had experienced KF, 1,083 had experienced the CKE, and 680 had died. Analytical Approach: Time-to-event analyses using multivariable proportional hazard regression models in a discovery-replication - replication design with external validation. Results: 5,088 GCKD study participants were included in analyses of urine metabolites, and 5,144 were included in analyses of plasma metabolites. Among 182 unique metabolites, 30 were significantly fi cantly associated with KF, 49 with the CKE, and 163 with death. The strongest association with KF was observed for plasma hydroxyasparagine (HR, 1.95; 95% CI, 1.682.25). An unnamed metabolite measured in plasma and urine was significantly fi cantly associated with KF, the CKE, and death. External validation of the identified fi ed associations of metabolites with KF or the CKE revealed directional consistency for 88% of observed associations. Selected associations of 18 metabolites with study outcomes have not been previously reported. Limitations: Use of observational data and semiquantitative metabolite measurements at a single time point. Conclusions: The observed associations between metabolites and KF, the CKE, or death in persons with CKD confirmed fi rmed previously reported fi ndings and also revealed several associations not previously described. These fi ndings warrant confirmatory fi rmatory research in other study cohorts.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PREDICTIVE MODEL; PROGRESSION; RISK; CKD; METABOLOMICS; BIOMARKERS; HAZARDS; GCKD; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Jan 2026 08:14 |
| Last Modified: | 16 Jan 2026 08:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65040 |
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