Five‐Aminolevulinic Acid as a Potential Biomarker for Renal Insufficiency After Heart Transplantation

ABSTRACT Renal complications are common following heart transplantation and lead to increased morbidity and mortality. The incidence of renal insufficiency is 10%–40% at 3–7 years after transplantation. This study aims to conduct metabolic profiling of serum samples from heart transplantation recipients to uncover differential metabolites related to renal insufficiency and potential pathogenic mechanisms. A total of 101 heart transplantation recipients were included and categorized into three groups according to their estimated glomerular filtration rate. The demographic and clinical data were collected at the time of sample collection. Plasma samples were collected and analyzed using liquid chromatography‐tandem mass spectrometry. The untargeted metabolomics revealed that during the progression of renal injury, 35 metabolites were upregulated and 1 metabolite was downregulated. Among them, the univariate analysis demonstrated that 13 differential metabolites had AUC ≥ 0.80 in both Stage 3 versus Stage 1 and Stage 3 versus Stage 2. Furthermore, enriched pathway analysis revealed that the differential metabolites among the three groups are mainly associated with ascorbate and aldarate metabolism, glycine, serine, and threonine metabolism, protein digestion and absorption, and biosynthesis of amino acids. Our findings indicate a strong association between creatinine and 5‐aminolevulinic acid with the occurrence and progression of renal insufficiency following heart transplantation. These results offer valuable insights into the underlying mechanisms contributing to renal dysfunction in heart transplantation recipients from a metabolomics perspective, thereby supporting improved prediction and treatment strategies for renal insufficiency posttransplantation.