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

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, Jérôme 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. 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 A. A. Campbell, Fathi Karouia, Vidya Mohamed-Alis, Samuel Rodriques, Steven Lynham, Joel Ricky Steele, Sergio Baranzini, Hossein Fazelinia, Zhongquan Dai, Akira Uruno, Dai Shiba, Masayuki Yamamoto, Eduardo A.C.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 and Stephen B. Walsh ()
Additional contact information
Keith Siew: University College London
Kevin A. Nestler: The George Washington University
Charlotte Nelson: University of California San Francisco
Viola D’Ambrosio: University College London
Chutong Zhong: University College London
Zhongwang Li: University College London
Alessandra Grillo: University College London
Elizabeth R. Wan: University College London
Vaksha Patel: University College London
Eliah Overbey: Weill Cornell Medical College
JangKeun Kim: Weill Cornell Medical College
Sanghee Yun: University of Pennsylvania Perelman School of Medicine
Michael B. Vaughan: University College Cork
Chris Cheshire: The Francis Crick Institute
Laura Cubitt: The Francis Crick Institute
Jessica Broni-Tabi: University College London
Maneera Yousef Al-Jaber: Anti-Doping Laboratory Qatar
Valery Boyko: NASA Ames Research Center
Cem Meydan: Weill Cornell Medical College
Peter Barker: University of Cambridge
Shehbeel Arif: Children’s Hospital of Philadelphia
Fatemeh Afsari: University of Florida
Noah Allen: Rensselaer Polytechnic Institute
Mohammed Al-Maadheed: Anti-Doping Laboratory Qatar
Selin Altinok: The University of North Carolina at Chapel Hill
Nourdine Bah: The Francis Crick Institute
Samuel Border: University of Florida
Amanda L. Brown: The University of North Carolina at Chapel Hill
Keith Burling: University of Cambridge
Margareth Cheng-Campbell: Rensselaer Polytechnic Institute
Lorianna M. Colón: Children’s Hospital of Philadelphia Research Institute
Lovorka Degoricija: NASA Ames Research Center
Nichola Figg: University of Cambridge
Rebecca Finch: Staffordshire University
Jonathan Foox: Weill Cornell Medical College
Pouya Faridi: Monash University
Alison French: NASA Ames Research Center
Samrawit Gebre: NASA Ames Research Center
Peter Gordon: University College London
Nadia Houerbi: Weill Cornell Medical College
Hossein Valipour Kahrood: Monash University
Frederico C. Kiffer: Children’s Hospital of Philadelphia
Aleksandra S. Klosinska: University of Cambridge
Angela Kubik: Rensselaer Polytechnic Institute
Han-Chung Lee: Monash University
Yinghui Li: China Astronaut Research and Training Center
Nicholas Lucarelli: University of Florida
Anthony L. Marullo: University College Cork
Irina Matei: Cornell University
Colleen M. McCann: The University of North Carolina at Chapel Hill
Sayat Mimar: University of Florida
Ahmed Naglah: University of Florida
Jérôme Nicod: The Francis Crick Institute
Kevin M. O’Shaughnessy: University of Cambridge
Lorraine Christine De Oliveira: Blue Marble Space Institute of Science
Leah Oswalt: The University of North Carolina at Chapel Hill
Laura Ioana Patras: Weill Cornell Medical College
San-huei Lai Polo: NASA Ames Research Center
María Rodríguez-Lopez: The Francis Crick Institute
Candice Roufosse: Imperial College London
Omid Sadeghi-Alavijeh: University College London
Rebekah Sanchez-Hodge: The University of North Carolina at Chapel Hill
Anindya S. Paul: University of Florida
Ralf Bernd Schittenhelm: Monash University
Annalise Schweickart: Weill Cornell Medical College
Ryan T. Scott: NASA Ames Research Center
Terry Chin Choy Lim Kam Sian: Monash University
Willian A. Silveira: Staffordshire University
Hubert Slawinski: The Francis Crick Institute
Daniel Snell: The Francis Crick Institute
Julio Sosa: University Health Network
Amanda M. Saravia-Butler: NASA Ames Research Center
Marshall Tabetah: Purdue University
Erwin Tanuwidjaya: Monash University
Simon Walker-Samuel: University College London
Xiaoping Yang: King’s College London
Yasmin: University of Cambridge
Haijian Zhang: Monash University
Jasminka Godovac-Zimmermann: University College London
Pinaki Sarder: University of Florida
Lauren M. Sanders: NASA Ames Research Center
Sylvain V. Costes: NASA Ames Research Center
Robert A. A. Campbell: University College London
Fathi Karouia: Blue Marble Space Institute of Science
Vidya Mohamed-Alis: Anti-Doping Laboratory Qatar
Samuel Rodriques: The Francis Crick Institute
Steven Lynham: King’s College London
Joel Ricky Steele: Monash University
Sergio Baranzini: University of California San Francisco
Hossein Fazelinia: Children’s Hospital of Philadelphia Research Institute
Zhongquan Dai: China Astronaut Research and Training Center
Akira Uruno: Tohoku Medical Megabank Organization, Tohoku University, Sendai
Dai Shiba: Japan Aerospace Exploration Agency (JAXA)
Masayuki Yamamoto: Tohoku Medical Megabank Organization, Tohoku University, Sendai
Eduardo A.C.Almeida: NASA Ames Research Center
Elizabeth Blaber: Rensselaer Polytechnic Institute
Jonathan C. Schisler: The University of North Carolina at Chapel Hill
Amelia J. Eisch: Children’s Hospital of Philadelphia
Masafumi Muratani: University of Tsukuba
Sara R. Zwart: University of Texas Medical Branch
Scott M. Smith: NASA Johnson Space Center
Jonathan M. Galazka: NASA Ames Research Center
Christopher E. Mason: Weill Cornell Medical College
Afshin Beheshti: NASA Ames Research Center
Stephen B. Walsh: University College London

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49212-1

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