Early identification of diabetic kidney disease (DKD) remains important in patients with type 2 diabetes mellitus (T2DM), particularly as renal dysfunction progresses before advanced clinical manifestations develop. A study published in Diabetes, Metabolic Syndrome and Obesity evaluated the potential utility of 2 gut microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln), for identifying DKD in patients with T2DM.

The analysis included 165 patients with T2DM, including 63 without nephropathy and 102 with DKD. Plasma TMAO and PAGln concentrations were measured using liquid chromatography-tandem mass spectrometry. Correlation, multivariable logistic regression, and receiver operating characteristic (ROC) analyses were performed to assess associations with renal function and DKD identification.

Findings

• Patients with DKD showed significantly higher plasma TMAO and PAGln levels compared with patients with T2DM without nephropathy.
• Both metabolites showed positive correlations with blood urea nitrogen, serum creatinine, uric acid, microalbuminuria, and urine albumin-to-creatinine ratio, and negative correlations with estimated glomerular filtration rate.
• TMAO and PAGln each emerged as independent correlates of DKD in multivariable analysis.
• ROC analysis showed area under the curve (AUC) values of 0.795 for TMAO and 0.832 for PAGln.
• Combined analysis of TMAO and PAGln increased the AUC to 0.846 and improved sensitivity to 75.6%, compared with 65.7% for TMAO alone and 68.3% for PAGln alone, while maintaining specificity of 85.2%.

TMAO and PAGln were independently associated with DKD in patients with T2DM and demonstrated potential utility as noninvasive biomarkers of renal involvement. Combined metabolite assessment improved sensitivity for DKD identification while maintaining high specificity.