# Metabolomics for Preclinical Detection of Diabetic Kidney Disease: A Comprehensive Review

## TL;DR

This paper reviews how metabolomics can detect early signs of diabetic kidney disease before significant kidney damage occurs.

## Contribution

The paper provides a comprehensive synthesis of metabolomic evidence for early detection of diabetic kidney disease.

## Key findings

- Early biochemical changes in energy metabolism are linked to future DKD risk.
- Metabolomic biomarkers may allow non-invasive early detection and better risk stratification.
- Perturbations in amino acid and urea cycle pathways are associated with DKD progression.

## Abstract

Diabetic kidney disease (DKD) affects up to 40% of individuals with diabetes and remains the leading cause of end-stage renal disease worldwide. Current biomarkers, such as albuminuria and estimated glomerular filtration rate, detect disease only after substantial kidney injury, limiting early intervention. Metabolomics offers unique potential to identify early biochemical changes preceding the clinical onset of DKD. This review synthesizes evidence from animal and human studies in diabetes without overt kidney disease, highlighting early perturbations in energy metabolism (TCA cycle, beta-oxidation, glycolysis) as well as alterations in amino acid, nucleotide and urea cycle pathways associated with future DKD risk. We discuss methodological considerations, translational relevance, and current research gaps and outline strategies for integrating metabolomics into predictive diagnostics. Early, non-invasive metabolic biomarkers may enable more precise risk stratification and timely intervention to improve patient outcomes.