2d13123908a108849bbf3bfa6e41b0a9 sfae366.pdf b4f8eb7e3a592399eb958d50c93ec47356a047a4 sfae366.pdf 738fcd6db0a9a1bdec14f78d8425b76d59303460c1bf36df6e91694ca12966f2 sfae366.pdf Title: Frailty and sarcopenia metabolomic signatures in kidney transplant candidates: the FRAILMar study Subject: DOI: 10.1093/ckj/sfae366 Clinical Kidney Journal, 18, 1, 23-11-2024. Abstract: 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.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.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.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. Keywords: chronic kidney disease, frailty, metabolomics, sarcopenia, transplant Author: Madrid-Gambin Francisco, Pérez-Sáez María José, Gómez-Gómez Alex, Haro Noemí, Redondo-Pachón Dolores, Dávalos-Yerovi Vanessa, Marco Ester, Crespo Marta, Pozo Oscar J., Pascual Julio, , Pérez-Sáez María José, Chamoun Betty, Redondo Dolores, Barbosa Francesc, Cao Higini, Collado Silvia, Buxeda Anna, Burballa Carla, Crespo Marta, Pascual Julio, Faura Anna, Vera María, Bach Anna, Pedreira Guillermo, Junyent Ernestina, Folgueiras Montserrat, Castillo Yolanda, Martínez Aida, Fernández Marisol, Barbero Eva, Fernández Noelia, Calvo Alicia, Carazo Jesús, Frances Albert, Cecchini Lluis, Marco Ester, Muñoz Elena, Delcros-Forestier Lou, de Valderrama Delky Meza, Morgado Andrea, Nogués Xavier, Rodríguez-Mañas Leocadio, Vázquez Olga, Muns María Dolores, Gárriz Miguel, Gómez María Polo, Hurtado Sara, López Maite, Ribera Laura, Guino Margarita, Roca Ramón, Calls Jordi, Rovira Alicia, Mora Josep, Ibrik Omar, Liria Florentina, López Thaïs, Almirall Jaume, Moya Carmen, Moreno Fátima, de Arellano Manel Ramírez, Rubio Sandra, Cidraque Ignacio, Pájaro Carlota, Garra Núria, Galcerán Josep, Fenollar Marina, Outón Sara, Jara Josep, García Rosa, Manresa Mònica Creator: OUP Producer: Acrobat Distiller 10.0.0 (Windows) CreationDate: Thu Jan 9 10:52:33 2025 CET ModDate: Thu Jan 9 10:53:13 2025 CET Custom Metadata: yes Metadata Stream: yes Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 612.284 x 790.866 pts Page rot: 0 File size: 1106752 bytes Optimized: yes PDF version: 1.3 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LLHBDC+CMSY10 Type 1C Custom yes yes yes 1647 0 LLGPPH+CaeciliaLTStd-Bold Type 1C WinAnsi yes yes no 1652 0 LLHAFG+MTSY Type 1C Custom yes yes yes 1655 0 LLGPPE+CaeciliaLTStd-Italic Type 1C WinAnsi yes yes no 1660 0 LLGPPG+CaeciliaLTStd-Roman Type 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Title: MATERIALS AND METHODS Destination: section*.4 Item: Title: Study design and subjects Destination: section*.6 Item: Title: Frailty assessment Destination: section*.8 Item: Title: Sarcopenia assessment Destination: section*.10 Item: Title: Other assessments Destination: section*.12 Item: Title: Sample collection and metabolomics analysis Destination: section*.14 Item: Title: Statistical analysis Destination: section*.16 Item: Title: RESULTS Destination: section*.18 Item: Title: Description of the cohort Destination: section*.20 Item: Title: Metabolic features associated with frailty and sarcopenia Destination: section*.22 Item: Title: Unsupervised multi-modal integration revealed underlying metabolic phenotypes Destination: section*.24 Item: Title: DISCUSSION Destination: section*.26 Item: Title: CONCLUSION Destination: section*.28 Item: Title: Supplementary data Destination: section*.30 Item: Title: ACKNOWLEDGEMENTS Destination: section*.32 Item: Title: FUNDING Destination: section*.34 Item: Title: DATA AVAILABILITY STATEMENT Destination: section*.36 Item: Title: CONFLICT OF INTEREST STATEMENT Destination: section*.38 Item: Title: REFERENCES Destination: section*.40 Info: Title: Frailty and sarcopenia metabolomic signatures in kidney transplant candidates: the FRAILMar study Author: Madrid-Gambin Francisco, Pérez-Sáez María José, Gómez-Gómez Alex, Haro Noemí, Redondo-Pachón Dolores, Dávalos-Yerovi Vanessa, Marco Ester, Crespo Marta, Pozo Oscar J., Pascual Julio, , Pérez-Sáez María José, Chamoun Betty, Redondo Dolores, Barbosa Francesc, Cao Higini, Collado Silvia, Buxeda Anna, Burballa Carla, Crespo Marta, Pascual Julio, Faura Anna, Vera María, Bach Anna, Pedreira Guillermo, Junyent Ernestina, Folgueiras Montserrat, Castillo Yolanda, Martínez Aida, Fernández Marisol, Barbero Eva, Fernández Noelia, Calvo Alicia, Carazo Jesús, Frances Albert, Cecchini Lluis, Marco Ester, Muñoz Elena, Delcros-Forestier Lou, de Valderrama Delky Meza, Morgado Andrea, Nogués Xavier, Rodríguez-Mañas Leocadio, Vázquez Olga, Muns María Dolores, Gárriz Miguel, Gómez María Polo, Hurtado Sara, López Maite, Ribera Laura, Guino Margarita, Roca Ramón, Calls Jordi, Rovira Alicia, Mora Josep, Ibrik Omar, Liria Florentina, López Thaïs, Almirall Jaume, Moya Carmen, Moreno Fátima, de Arellano Manel Ramírez, Rubio Sandra, Cidraque Ignacio, Pájaro Carlota, Garra Núria, Galcerán Josep, Fenollar Marina, Outón Sara, Jara Josep, García Rosa, Manresa Mònica Subject: DOI: 10.1093/ckj/sfae366 Clinical Kidney Journal, 18, 1, 23-11-2024. Abstract: 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.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.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.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. Keywords: chronic kidney disease, frailty, metabolomics, sarcopenia, transplant Creator: OUP Producer: Acrobat Distiller 10.0.0 (Windows) CreationDate: Thu Jan 09 11:22:33 CET 2025 ModDate: Thu Jan 09 11:23:13 CET 2025 ID: 0x57784cadf14678b924b90f6bdc90cc7e, 0xef12fafeae22e22d57d4bd3a431acea4 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 143 ImageHeight: 151 ColorSpace: CMYK BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1260 ImageHeight: 1152 BitsPerSample: 8 BitsPerSampleUnit: integer Intent: RelativeColorimetric Interpolate: true Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1332 ImageHeight: 1654 BitsPerSample: 8 BitsPerSampleUnit: integer Intent: RelativeColorimetric Interpolate: true Fonts: Type1: Font: BaseFont: LLHBLP+CaeciliaLTStd-Heavy FontSubset: true FirstChar: 48 LastChar: 89 FontDescriptor: FontName: LLHBLP+CaeciliaLTStd-Heavy Flags: Nonsymbolic, ForceBold FontBBox: -170, -277, 1146, 970 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: LLGPPH+CaeciliaLTStd-Bold FontSubset: true FirstChar: 40 LastChar: 121 FontDescriptor: FontName: LLGPPH+CaeciliaLTStd-Bold Flags: Serif, Nonsymbolic, ForceBold FontBBox: -166, -273, 1141, 938 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: LLGPPF+dummy-space FontSubset: true FirstChar: 32 LastChar: 32 FontDescriptor: FontName: LLGPPF+dummy-space Flags: Nonsymbolic FontBBox: 0, 0, 0, 0 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: LLHAFG+MTSY FontSubset: true FirstChar: 2 LastChar: 177 FontDescriptor: FontName: LLHAFG+MTSY Flags: Symbolic FontBBox: 0, -954, 1043, 796 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: LLHCHM+RMTMI FontSubset: true FirstChar: 2 LastChar: 181 FontDescriptor: FontName: LLHCHM+RMTMI Flags: Symbolic, Italic FontBBox: 0, -213, 987, 680 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: LLGPPE+CaeciliaLTStd-Italic FontSubset: true FirstChar: 45 LastChar: 241 FontDescriptor: FontName: LLGPPE+CaeciliaLTStd-Italic Flags: Serif, Nonsymbolic, Italic FontBBox: -166, -270, 1053, 915 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: LLHBDC+CMSY10 FontSubset: true FirstChar: 129 LastChar: 129 FontDescriptor: FontName: LLHBDC+CMSY10 Flags: Symbolic, Italic FontBBox: -29, -960, 1116, 775 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: LLGPPG+CaeciliaLTStd-Roman FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: LLGPPG+CaeciliaLTStd-Roman Flags: Serif, Symbolic FontBBox: -167, -270, 1136, 926 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true XMP: 2025-01-09T15:22:33+05:30 2025-01-09T15:23:13+05:30 2025-01-09T15:23:13+05:30 OUP Acrobat Distiller 10.0.0 (Windows) chronic kidney disease, frailty, metabolomics, sarcopenia, transplant VoR 10.1093/ckj/sfae366 2048-8513 Clinical Kidney Journal journal 18 10.1093/ckj/sfae366 https://doi.org/10.1093/ckj/sfae366 © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com All Rights Reserved application/pdf doi:10.1093/ckj/sfae366 © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Madrid-Gambin Francisco Pérez-Sáez María José Gómez-Gómez Alex Haro Noemí Redondo-Pachón Dolores Dávalos-Yerovi Vanessa Marco Ester Crespo Marta Pozo Oscar J. Pascual Julio Pérez-Sáez María José Chamoun Betty Redondo Dolores Barbosa Francesc Cao Higini Collado Silvia Buxeda Anna Burballa Carla Crespo Marta Pascual Julio Faura Anna Vera María Bach Anna Pedreira Guillermo Junyent Ernestina Folgueiras Montserrat Castillo Yolanda Martínez Aida Fernández Marisol Barbero Eva Fernández Noelia Calvo Alicia Carazo Jesús Frances Albert Cecchini Lluis Marco Ester Muñoz Elena Delcros-Forestier Lou de Valderrama Delky Meza Morgado Andrea Nogués Xavier Rodríguez-Mañas Leocadio Vázquez Olga Muns María Dolores Gárriz Miguel Gómez María Polo Hurtado Sara López Maite Ribera Laura Guino Margarita Roca Ramón Calls Jordi Rovira Alicia Mora Josep Ibrik Omar Liria Florentina López Thaïs Almirall Jaume Moya Carmen Moreno Fátima de Arellano Manel Ramírez Rubio Sandra Cidraque Ignacio Pájaro Carlota Garra Núria Galcerán Josep Fenollar Marina Outón Sara Jara Josep García Rosa Manresa Mònica Oxford University Press DOI: 10.1093/ckj/sfae366 Clinical Kidney Journal, 18, 1, 23-11-2024. Abstract: 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.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.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.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. chronic kidney disease frailty metabolomics sarcopenia transplant Frailty and sarcopenia metabolomic signatures in kidney transplant candidates: the FRAILMar study Madrid-Gambin Francisco, Pérez-Sáez María José, Gómez-Gómez Alex, Haro Noemí, Redondo-Pachón Dolores, Dávalos-Yerovi Vanessa, Marco Ester, Crespo Marta, Pozo Oscar J., Pascual Julio, , Pérez-Sáez María José, Chamoun Betty, Redondo Dolores, Barbosa Francesc, Cao Higini, Collado Silvia, Buxeda Anna, Burballa Carla, Crespo Marta, Pascual Julio, Faura Anna, Vera María, Bach Anna, Pedreira Guillermo, Junyent Ernestina, Folgueiras Montserrat, Castillo Yolanda, Martínez Aida, Fernández Marisol, Barbero Eva, Fernández Noelia, Calvo Alicia, Carazo Jesús, Frances Albert, Cecchini Lluis, Marco Ester, Muñoz Elena, Delcros-Forestier Lou, de Valderrama Delky Meza, Morgado Andrea, Nogués Xavier, Rodríguez-Mañas Leocadio, Vázquez Olga, Muns María Dolores, Gárriz Miguel, Gómez María Polo, Hurtado Sara, López Maite, Ribera Laura, Guino Margarita, Roca Ramón, Calls Jordi, Rovira Alicia, Mora Josep, Ibrik Omar, Liria Florentina, López Thaïs, Almirall Jaume, Moya Carmen, Moreno Fátima, de Arellano Manel Ramírez, Rubio Sandra, Cidraque Ignacio, Pájaro Carlota, Garra Núria, Galcerán Josep, Fenollar Marina, Outón Sara, Jara Josep, García Rosa, Manresa Mònica uuid:16be7df2-8a7d-3c90-8d16-548b903fdac0 uuid:35e5fb65-bce3-4816-9a8c-91b91dce4715 True Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 62, 683, 116, 694 Annotation: Subtype: Link Rect: 314, 709, 426, 719 Annotation: Subtype: Link Rect: 229, 539, 243, 555 Annotation: Subtype: Link Rect: 241, 544, 248, 557 Destination: 1612 Annotation: Subtype: Link Rect: 249, 544, 256, 557 Destination: 1612 Annotation: Subtype: Link Rect: 401, 539, 415, 555 Annotation: Subtype: Link Rect: 413, 544, 421, 557 Destination: 1612 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