The Role of Amino Acid Metabolism in Autosomal Dominant Polycystic Kidney Disease Progression

Introduction: Amino acid metabolism is crucial for human health and well-being, as amino acids serve as the fundamental components of proteins and fulfill various essential functions in the body [1-2]. The aim of this study was to perform quantification of serum amino acid levels in Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients and to compare them according to clinical outcomes of disease progression (slow and rapid progression), development of hypertension (present/absent) and mortality (ex and survived). Methods: Serum blood samples for metabolomic analyses were obtained from 254 patients who were diagnosed with ADPKD in Erciyes University Faculty of Medicine, Nephrology Clinic, who were still being followed up during the study period. The serum amino acid profile was determined using liquid chromatography Tandem Mass Spectrometry (LC-MS/MS). Results: Isoleucyl-Proline and L-Glutamine metabolic profiles in patients with rapid progression of ADPKD differ significantly from those in the slow progression group. Isoleucyl-Proline levels were elevated in the rapid progression group, whereas L-Glutamine levels were higher in the slow progression group. Significant differences were observed in the levels of 4-Methylaminobutyrate, Acetyl-L-arginine, Alanine, Isoleucyl-proline, L-Carnitine, and L-Tryptophan in patients who died. Additionally, significant differences were found in the levels of Acetyl-L-arginine, Asparagine, Hydroxyarginine, Isoleucine, Isoleucyl-proline, and L-Lysine in patients with hypertension compared to those without hypertension. Distinct metabolic reprogramming is evident, particularly involving alterations in alanine and asparagine metabolism. These metabolic shifts are closely linked to the molecular mechanisms driving the disease. Furthermore, statistically significant associations were identified between specific amino acids levels. Conclusion: Investigating innovative therapeutic and diagnostic approaches targeting specific amino acids could provide promising avenues for reducing disease severity. These findings enhance our comprehension of the complex interplay between amino acid metabolism and overall health, laying the groundwork for future studies focused on advancing disease detection and management strategies.