Abstract Background End-stage kidney disease (ESKD) significantly increases cardiovascular disease (CVD) risk and worsens prognosis, demanding refined risk stratification and subsequent timely intervention. While blood amino acid (AA) profiling has shown promise in CVD risk prediction, its clinical utility in ESKD patients with CVD remains unexplored. Aim To examine whether distinctive blood AA profiles can be identified in ESKD patients with CVD and whether their profiles can stratify the high-risk group for future adverse cardiovascular events in ESKD patients with CVD. Methods We enrolled 573 patients (mean age: 71 years; 38% male) hospitalized for CVD in our University Hospital between January 2022 and December 2023. Fasting plasma levels of 39 AA metabolites were measured using liquid chromatography-mass spectrometry, and hierarchical clustering analysis (HCA) was applied to analyze metabolite data comprehensively. Through the investigation of the association between chronic kidney disease (CKD) stage (G1-G2, n=258; G3-G4, n=259; G5 (ESKD), n=56 dialysis, n=51; non-dialysis, n=5) based on estimated glomerular filtration ratio and the HCA results, the ESKD-specific AA profiles were explored. Using Kaplan-Meier (KM) analysis, the 1-year incidence of major adverse cardiovascular events (MACE; all-cause mortality, nonfatal myocardial infarction, ischemic stroke, and rehospitalization for worsening heart failure) was compared across the CKD stages, and the prognostic value of AA profiles was assessed for each CKD stage. Results HCA enabled the identification of four AA clusters, and ESKD patients exhibited a distinct cluster, which was characterized by lower values of essential AA/non-essential AA ratio, branched chain AA/total AA ratio, and Fischer ratio than those of patients with other CKD stages (p0.0001, p 0.0001, and p=0.0002, respectively). During the observational period, 58 patients developed MACE, and the prognosis of ESKD patients was significantly worse than that of the patients with other CKD stages (log-lank test, p0.0001). Among the ESKD patients, a discriminatory ability for the incidence of MACE was found in the Fischer ratio (a cut-off value, 2.84; AUC, 0.69; p=0.01) but not in other AA parameters. Moreover, the group with a Fischer ratio 2.84 showed a significantly worse prognosis than the group with a Fischer ratio ≥ 2.84 only in ESKD patients (log-lank test, p=0.0007) but not in patients with other CKD stages. Conclusion ESKD-specific AA profile and the prognostic utility of the Fischer ratio suggest that blood AA profiling might provide better risk stratification in ESKD patients with CVD.
Moribayashi et al. (2025) studied this question.