Abstract: TH-OR023
Pathway Analysis of Cosmic Kidney Disease: Just How Bad Does Spaceflight Get?
Session Information
- Fluids and Electrolytes: Bench and Bedside
November 06, 2025 | Location: Room 361A, Convention Center
Abstract Time: 05:10 PM - 05:20 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- D'Ambrosio, Viola, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
- Siew, Keith, University College London, London, England, United Kingdom
Background
Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney were largely unexplored. To address this, our group conducted an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction, and described “Cosmic Kidney Disease” as a previously unknown risk factor for astronauts [https://doi.org/10.1038/s41467-024-49212-1]
However, we did not address the potential magnitude of pathway dysregulation induced by spaceflight conditions. The aim of the current work is to re-interrogate our data to explore and attempt to quantify this
Methods
Previously, we performed biomolecular, clinical chemistry and morphometry analyses using samples and datasets available from 11 spaceflightexposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR exposed mouse missions.
These data were analysed with Metascape [https://metascape.org/] using databases and tools such as GO, KEGG, DisGeNET, STRING/Cytoscape, etc. We also utilised SPOKE [https://spoke.ucsf.edu/] and DAG [https://dagitty.net/] tools to integrate non-omics data where possible.
Results
We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.
Re-interrogation of the data provided a new ranking of health consequences according to gene ratio (a metric of pathway dysactivity), cumulative pathway coverage and predicted severity
Conclusion
We have demonstrated that there is renal structural and functional remodelling likely caused by microgravity, probably synergistically with GCR. We have shown that this remodelling is a potential driver of kidney stone formation and many of the changes in the urinary biochemistry of humans and animals experienced by those exposed to spaceflight. We have also shown that acute exposure to simulated GCR causes both acute and chronic tubular epithelial and vascular damage that appears both progressive and irreversible.
Funding
- Government Support – Non-U.S.