Abstract
BACKGROUND: Sarcopenia and frailty are often overlooked in assessing kidney transplant (KT) candidates with chronic kidney disease (CKD), potentially leading to poor post-transplant outcomes. This study aimed to identify metabolites associated with frailty and sarcopenia in KT candidates from the FRAILMar study. METHODS: Between June 2016 and June 2020, we evaluated frailty and sarcopenia in 173 KT candidates using the Physical Frailty Phenotype and EGWSOP-2 criteria, respectively. Seventy-five metabolic markers from targeted pathways, previously linked to CKD, sarcopenia or frailty, were measured in serum samples. These markers were analyzed using adjusted and weighted generalized linear models. Metabolomic data were integrated with multi-modal data, such as comorbidities, using a factor-based integration algorithm to identify metabolic phenotypes. RESULTS: Increased metabolites related to energy metabolism and essential amino acids were associated with frailty, mainly Krebs cycle intermediates. Sarcopenic KT candidates showed lower levels of aromatic amino acids, and lower protein/muscle metabolism, energy metabolism and neurotransmission compared with non-sarcopenic patients. Unsupervised multi-modal integration revealed a high-risk metabolic phenotype characterized by the presence of sarcopenia, diabetes mellitus and low body mass index, with alterations in branched-chain amino acids and high activity of lactate dehydrogenase enzyme. CONCLUSIONS: Frailty and sarcopenia are common among KT candidates, and their metabolic status reveals notable disruptions in energy and amino acid metabolism. These findings highlight the value of a detailed metabolic assessment to more accurately evaluate patient health status prior to transplantation.