Urine Metabolites Could Forecast Renal Outcomes in T2D

Medscape

22-05-2025

Increased levels of urine metabolites choline and dimethylglycine were independently associated with an increased risk for renal events and all-cause mortality in patients with type 2 diabetes (T2D), with evidence suggesting that tubular stress partly mediated the link between disrupted choline metabolism and the gradual decline in kidney function in this population. METHODOLOGY: Although elevated plasma choline levels are linked to a greater risk for kidney disease progression in patients with T2D, the relationship between choline metabolism in the kidneys and the progression of kidney disease is not well understood.
Researchers analyzed data of 1894 patients with T2D (mean age, 57.4 years; 51.1% men) from a regional hospital and a primary care facility in Singapore to study the role of urine metabolites of the choline oxidation pathway in the progression of chronic kidney disease (CKD).
Urine metabolites (choline, betaine, dimethylglycine, and sarcosine) were quantified or semiquantified using liquid chromatography-mass spectrometry.
Variables such as heart conditions, blood pressure, tubulopathy biomarkers, and estimated glomerular filtration rate (eGFR) were either self-reported or measured, with patients being followed-up using electronic medical records and in-person research visits.
The primary outcome was a composite of incident end-stage kidney disease ­­(defined as having a sustained eGFR < 15 mL/min/1.73 m2, undergoing maintenance dialysis, or death from renal causes) or the doubling of serum creatinine levels. TAKEAWAY: Overall, 263 participants experienced renal events over a median follow-up of 9.2 years. Those who experienced renal events had higher baseline levels of urine choline (median, 32.1 vs 16.9 µM) and dimethylglycine (median, 1.25 vs 0.74 units) than those who did not.
Each SD increase in levels of urine choline (adjusted hazard ratio [aHR], 1.33) and dimethylglycine (aHR, 1.30) was associated with an increased risk for the composite renal outcome ( P < .001 for both).
< .001 for both). Researchers postulated that tubular stress may partly mediate the link between urine choline, dimethylglycine, and the risk for adverse renal outcome.
After adjusting for clinical risk factors, each SD increase in levels of urine choline and dimethylglycine was associated with a 1.2-fold and 1.17-fold increase in the risk for all-cause death, respectively ( P < .05 for both). IN PRACTICE:
'High levels of urine choline and dimethylglycine in the choline oxidation pathway were strongly associated with a high risk for CKD progression independent of traditional risk factors in individuals with type 2 diabetes. Dysregulation of choline metabolism in the kidney may be involved in pathogenesis of tubulopathy and plays a role in progressive loss of kidney disease,' the authors wrote. SOURCE:
This study was led by Jian-Jun Liu, Clinical Research Unit, Khoo Teck Puat Hospital (KTPH) in Singapore. It was published online on May 13, 2025, in Journal of Clinical Endocrinology & Metabolism . LIMITATIONS:
It could not be inferred whether urine metabolites caused kidney disease progression. Residual confounding could not be ruled out due to observational nature of this study. Some of the urine metabolites were semiquantified with relatively high technical differences. DISCLOSURES:
This study received grants from KTPH STAR and Singapore National Medical Research Council. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
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Cite this: Urine Metabolites Could Forecast Renal Outcomes in T2D - Medscape - May 22, 2025.