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Abstract: FR-PO1015

Cosmic Kidney Disease: A Pan-Omic Investigation of the Health Consequence of a Trip to Mars and Back

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Siew, Keith, University College London, London, United Kingdom
  • Walsh, Stephen B., University College London, London, United Kingdom

Group or Team Name

  • London Tubular Centre.
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 are largely unexplored.

Methods

We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions.

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.

Conclusion

This study is the largest to ever look at the effect of spaceflight on kidney function. 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.