ArticleAmerican journal of nephrology2022
High-Throughput Metabolomics and Diabetic Kidney Disease Progression: Evidence from the Chronic Renal Insufficiency (CRIC) Study.
Article in American journal of nephrology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Digitally enhanced ketogenic diet versus low-fat diet for cardio-renal-metabolic health in a predominantly Hispanic adult population with overweight or obesity: Pilot randomised clinical trial.Diabetes, obesity & metabolism · 2025Trial
- Predictive value of kynurenine pathway metabolites in patients with diabetic kidney disease.Acta diabetologica · 2026Article
- Lifestyles, metabolome and diabetic kidney disease: a cohort study.QJM : monthly journal of the Association of Physicians · 2026Article
- Spatial metabolomics: A new tool for unravelling the metabolic disorders and heterogeneity in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Spatial metabolomics and multiomics integration for breakthroughs in precision medicine for kidney disease.Nature reviews. Nephrology · 2026Review
- Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps.Clinical kidney journal · 2026Review
- Urine as a source of biomarkers and biological knowledge in chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Comprehensive and quantitative urinary metabolomic profiling for improved characterization of diabetic nephropathy.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Quinolinic acid potentially links kidney injury to brain toxicity.JCI insight · 2025Article
- Multi-Omics Integration in Nephrology: Advances, Challenges, and Future Directions.Seminars in nephrology · 2024Review
- A global perspective on the status of clinical metabolomics in laboratory medicine - a survey by the IFCC metabolomics working group.Clinical chemistry and laboratory medicine · 2024Article
- An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples.Metabolites · 2024Review
- Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification.Molecules (Basel, Switzerland) · 2024Review
- Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children.Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation · 2024Article
- Adenine crosses the biomarker bridge: from 'omics to treatment in diabetic kidney disease.The Journal of clinical investigation · 2023Article
- Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients.The Journal of clinical investigation · 2023Article
- CKD Urine Metabolomics: Modern Concepts and Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Review
- Serum and urine metabolomic biomarkers for predicting prognosis in patients with immunoglobulin A nephropathy.Kidney research and clinical practice · 2023Article
- Point-of-care applicable metabotyping using biofluid-specific electrospun MetaSAMPs directly amenable to ambient LA-REIMS.Science advances · 2023Article
- Clinical prediction model for prognosis in kidney transplant recipients (KIDMO): study protocol.Diagnostic and prognostic research · 2023Article
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 2 countries.
Funding
Abstract
introductionMetabolomics could offer novel prognostic biomarkers and elucidate mechanisms of diabetic kidney disease (DKD) progression. Via metabolomic analysis of urine samples from 995 CRIC participants with diabetes and state-of-the-art statistical modeling, we aimed to identify metabolites prognostic to DKD progression.
methodsUrine samples (N = 995) were assayed for relative metabolite abundance by untargeted flow-injection mass spectrometry, and stringent statistical criteria were used to eliminate noisy compounds, resulting in 698 annotated metabolite ions. Utilizing the 698 metabolites' ion abundance along with clinical data (demographics, blood pressure, HbA1c, eGFR, and albuminuria), we developed univariate and multivariate models for the eGFR slope using penalized (lasso) and random forest models. Final models were tested on time-to-ESKD (end-stage kidney disease) via cross-validated C-statistics. We also conducted pathway enrichment analysis and a targeted analysis of a subset of metabolites.
resultsSix eGFR slope models selected 9-30 variables. In the adjusted ESKD model with highest C-statistic, valine (or betaine) and 3-(4-methyl-3-pentenyl)thiophene were associated (p < 0.05) with 44% and 65% higher hazard of ESKD per doubling of metabolite abundance, respectively. Also, 13 (of 15) prognostic amino acids, including valine and betaine, were confirmed in the targeted analysis. Enrichment analysis revealed pathways implicated in kidney and cardiometabolic disease.
conclusionsUsing the diverse CRIC sample, a high-throughput untargeted assay, followed by targeted analysis, and rigorous statistical analysis to reduce false discovery, we identified several novel metabolites implicated in DKD progression. If replicated in independent cohorts, our findings could inform risk stratification and treatment strategies for patients with DKD.
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