Keto-gluconeogenic metabolic axis mirrors renal homeostasis and post-injury response in spatial transcriptomics
- 1National Institute of Health and Medical Research (INSERM), UMR-S1155, Tenon Hospital, Faculty of Medicine, Sorbonne University, Paris, France
Abstract
Metabolic disturbance is a key feature in acute kidney injury (AKI) and chronic kidney disease (CKD). The kidney highly depends on fatty acid metabolism; how renal cells rewire metabolism upon AKI and CKD transition remained unclear. Here, we combine spatial transcriptomics with biochemical analyses to characterize metabolic changes and intercellular interactions during AKI to CKD transition. Using aristolochic acid model of CKD, we spatio-temporally correlated changes in structure and function with metabolic profile during AKI to CKD transition. Surprisingly, keto-gluconeogenic metabolic axis was highly enriched in healthy kidney and paralleled injury phase transitions. Intercellular interaction analysis associated a subtype of macrophage with the drift to chronicity. Online scRNAseq datasets analysis confirmed altered keto-gluconeogenic metabolic pathways in ischemia-reperfusion injured mouse kidneys and AKI and CKD human kidney biopsies compared to healthy controls. This study identifies a metabolic axis transcriptionally mirroring renal homeostasis and injury responses, and tubulo-interstitial interactions that can be targeted to mitigate AKI to CKD transition.
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BibTeX
@misc{gueguen2026ketogluconeogenic,
title = {{Keto-gluconeogenic metabolic axis mirrors renal homeostasis and post-injury response in spatial transcriptomics}},
author = {P. Gueguen and J. Vouillamoz and S. Hadjadj and K. Spahic and R. H. Wenger and S. Nlandu Khodo},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.753087},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.753087v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Keto-gluconeogenic metabolic axis mirrors renal homeostasis and post-injury response in spatial transcriptomics
AU - P. Gueguen
AU - J. Vouillamoz
AU - S. Hadjadj
AU - K. Spahic
AU - R. H. Wenger
AU - S. Nlandu Khodo
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.753087
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.753087v1
AB - Metabolic disturbance is a key feature in acute kidney injury (AKI) and chronic kidney disease (CKD). The kidney highly depends on fatty acid metabolism; how renal cells rewire metabolism upon AKI and CKD transition remained unclear. Here, we combine spatial transcriptomics with biochemical analyses to characterize metabolic changes and intercellular interactions during AKI to CKD transition. Using aristolochic acid model of CKD, we spatio-temporally correlated changes in structure and function with metabolic profile during AKI to CKD transition. Surprisingly, keto-gluconeogenic metabolic axis was highly enriched in healthy kidney and paralleled injury phase transitions. Intercellular interaction analysis associated a subtype of macrophage with the drift to chronicity. Online scRNAseq datasets analysis confirmed altered keto-gluconeogenic metabolic pathways in ischemia-reperfusion injured mouse kidneys and AKI and CKD human kidney biopsies compared to healthy controls. This study identifies a metabolic axis transcriptionally mirroring renal homeostasis and injury responses, and tubulo-interstitial interactions that can be targeted to mitigate AKI to CKD transition.
ER -