Potential Diagnostic and Therapeutic Role of Amino Acids in Diabetic Kidney Disease: An Updated Review.

INTRODUCTION/OBJECTIVE: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Amino acids play a crucial role in both the diagnosis and treatment of DKD. This review examines the mechanism by which amino acids exert their biological effects and their relevance to the diagnosis and management of DKD. METHODS: A literature search was conducted using PubMed, Scopus, and Web of Science. Search terms included "DKD", "Type 2 Diabetes Mellitus (T2DM)", "Blood Pressure (B.P)", "Proteinuria", "microalbuminuria", "Inflammatory cytokines", "homocysteine", "nephrotoxicity", and "amino acids" used to identify relevant studies. Several studies demonstrated that amino acid supplementation attenuates serum transforming growth factor-β (TGF- β) levels and the urinary albumin- to-creatinine ratio, and improves metabolic parameters in patients with T2DM. Improvements in kidney function and B.P were also observed, suggesting that amino acid supplementation may prevent the progression of microalbuminuria. Patients with DKD exhibit altered levels of inflammatory cytokines and homocysteine. In some studies, combination therapy was more effective in reducing nephrotoxicity. RESULTS: Metabolomics profiling of urinary and serum metabolic pathways has emerged as a promising approach for identifying potential diagnostic biomarkers in patients with DKD. Candidate biomarkers include tryptophan, threonine, citrulline, methionine and homovanillic acid sulphate. Abnormal amino acid metabolism in DKD is associated with oxidative stress, inflammatory and immune dysregulation, mitochondrial dysfunction, iron death and dysregulated autophagy. DISCUSSION: Drugs that interrupt the renin-angiotensin- aldosterone system can help control these changes. Abnormal amino acid metabolism in DKD is closely linked to oxidative stress, inflammatory responses and immune responses, as well as mitochondrial dysfunction, iron death and impaired autophagy. CONCLUSION: Altered amino acid profiles in DKD may serve as early diagnostic markers. Metabolomic approaches enable detection of changes in non-essential amino acids and early kidney damage before the onset of proteinuria, reflecting changes in the local renal microenvironment that precede clinically detectable proteinuria.