Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

Siew, Keith; Nestler, Kevin A.; Nelson, Charlotte; D’Ambrosio, Viola; Zhong, Chutong; Li, Zhongwang; Grillo, Alessandra; Wan, Elizabeth R.; Patel, Vaksha; Overbey, Eliah; Kim, JangKeun; Yun, Sanghee; Vaughan, Michael B.; Cheshire, Chris; Cubitt, Laura; Broni-Tabi, Jessica; Al-Jaber, Maneera Yousef; Boyko, Valery; Meydan, Cem; Barker, Peter; Arif, Shehbeel; Afsari, Fatemeh; Allen, Noah; Al-Maadheed, Mohammed; Altinok, Selin; Bah, Nourdine; Border, Samuel; Brown, Amanda L.; Burling, Keith; Cheng-Campbell, Margareth; Colón, Lorianna M.; Degoricija, Lovorka; Figg, Nichola; Finch, Rebecca; Foox, Jonathan; Faridi, Pouya; French, Alison; Gebre, Samrawit; Gordon, Peter; Houerbi, Nadia; Valipour Kahrood, Hossein; Kiffer, Frederico C.; Klosinska, Aleksandra S.; Kubik, Angela; Lee, Han-Chung; Li, Yinghui; Lucarelli, Nicholas; Marullo, Anthony L.; Matei, Irina; McCann, Colleen M.; Mimar, Sayat; Naglah, Ahmed; Nicod, Jérôme; O’Shaughnessy, Kevin M.; Oliveira, Lorraine Christine De; Oswalt, Leah; Pa...

Abstract

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. 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. 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.

• Journal Article Type: Article
• Acceptance Date: May 28, 2024
• Online Publication Date: Jun 11, 2024
• Deposit Date: Oct 25, 2024
• Publicly Available Date: Oct 28, 2024
• Journal: Nature Communications
• Print ISSN: 2041-1723
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: 4923
• DOI: https://doi.org/10.1038/s41467-024-49212-1
• Additional Information: Received: 20 January 2024; Accepted: 28 May 2024; First Online: 11 June 2024; : C.A.N. and S.E.B. are cofounders and hold shares in MATE Bioservices, a company that commercialises uses of SPOKE knowledge graph. V.D.A. received consultancy fees from Allena Pharmaceuticals. C.M. is compensated by Thorne HealthTech. C.R. received Consultancy from Novartis. External Committee member in the Banff Foundation for Allograft Pathology, the Renal Pathology Society, the Royal College of Pathologists. P.S. is an equity holder in DigPath Inc, and currently he serves on the advisory board of the same incorporation. S.R. is an active shareholder in Curio Bio, which commercialises Slide-seq. C.E.M. is a co-Founder of Onegevity All other authors declare no competing interests.