Correlations Between Trimethylamine-N-Oxide, Megalin, Lysine and Markers of Tubular Damage in Chronic Kidney Disease
Abstract
Trimethylamine-N-oxide (TMAO), a gut microbiota-derived dietary metabolite, is linked to progression of chronic kidney disease (CKD). Megalin, a renal proximal tubule receptor crucial for albumin reabsorption, also plays a role in CKD. However, the relationship between them is not well explored. The aim of this study was to investigate if there are any correlations between the levels of TMAO, megalin, lysine and markers of tubular damage in CKD. Urinary metabolites (TMAO, choline, L-carnitine, betaine, lysine) and tubular markers (megalin, albumin, EGF, MCP-1) were quantified by LC-MS/MS and ELISA. Associations were evaluated using analysis of covariance (ANCOVA) adjusted for age and diabetes, with false discovery rate correction. Compared with controls, CKD patients showed higher urinary choline (FDR < 0.001), betaine (FDR = 0.007), lysine (FDR = 0.005), and soluble megalin (FDR < 0.001) but lower EGF and EGF/MCP-1 ratio (both FDR < 0.001). Correlation analyses revealed that serum TMAO was positively associated with soluble megalin and negatively with EGF/MCP-1 ratio. Choline, L-carnitine, and betaine were positively correlated with megalin. This cross-sectional study identifies associations between urinary metabolites, megalin, and tubular injury markers in advanced CKD. Although causality cannot be inferred, the results point to a potential metabolic–tubular link that should be explored in future longitudinal and mechanistic studies.
How strong is the evidence?
Evidence Hub reads this as a cross-sectional. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.
Read the paper
Related studies
- Diagnosis and management of glutaric aciduria type I – revised recommendations
- EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas
- Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency
- Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin
- Discovery of Novel Recurrent Mutations in Childhood Early T-Cell Precursor Acute Lymphoblastic Leukemia by Whole Genome Sequencing - a Report From the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.