Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction
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Keith Siew Kevin A Nestler Charlotte Nelson Viola D'Ambrosio Chutong Zhong Zhongwang Li Alessandra Grillo Elizabeth R Wan Vaksha Patel Eliah Overbey JangKeun Kim Sanghee Yun Michael B Vaughan Chris Cheshire Laura Cubitt Jessica Broni-Tabi Maneera Yousef Al-Jaber Valery Boyko Cem Meydan Peter Barker Shehbeel Arif Fatemeh Afsari Noah Allen Mohammed Al-Maadheed Selin Altinok Nourdine Bah Samuel Border Amanda L Brown Keith Burling Margareth Cheng-Campbell Lorianna M Colón Lovorka Degoricija Nichola Figg Rebecca Finch Jonathan Foox Pouya Faridi Alison French Samrawit Gebre Peter Gordon Nadia Houerbi Hossein Valipour Kahrood Frederico C Kiffer Aleksandra S Klosinska Angela Kubik Han-Chung Lee Yinghui Li Nicholas Lucarelli Anthony L Marullo Irina Matei Colleen M McCann Sayat Mimar Ahmed Naglah Jerome Nicod Kevin M O'Shaughnessy Lorraine Christine De Oliveira Leah Oswalt Laura Ioana Patras San-Huei Lai Polo María Rodríguez-Lopez Candice Roufosse Omid Sadeghi-Alavijeh Rebekah Sanchez-Hodge Anindya S Paul Ralf Bernd Schittenhelm Annalise Schweickart Ryan T Scott Terry Chin Choy Lim Kam Sian Willian A da Silveira Hubert Slawinski Daniel Snell Julio Sosa Amanda M Saravia-Butler Marshall Tabetah Erwin Tanuwidjaya Simon Walker-Samuel Xiaoping Yang Yasmin Haijian Zhang Jasminka Godovac-Zimmermann Pinaki Sarder Lauren M Sanders Sylvain V Costes Robert AA Campbell Fathi Karouia Vidya Mohamed-Alis Sam Rodriques Steven Lynham Joel Ricky Steele Sergio Baranzini Hossein Fazelinia Zhongquan Dai Akira Uruno Dai Shiba Masayuki Yamamoto Eduardo AC Almeida Elizabeth Blaber Jonathan C Schisler Amelia J Eisch Masafumi Muratani Sara R Zwart Scott M Smith Jonathan M Galazka Christopher E Mason Afshin Beheshti Stephen B Walsh
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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.
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Journal
Nature Communications
Volume
15
Issue number
1
Pages
4923
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10.1038/s41467-024-49212-1
Europe PubMed Central
38862484
Pubmed
38862484
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The publication was previously a preprint.
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