Nature Communications (Jun 2024)
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. 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 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,
- Stephen B. Walsh
Affiliations
- Keith Siew
- London Tubular Centre, Department of Renal Medicine, University College London
- Kevin A. Nestler
- The Institute for Biomedical Sciences (IBS), The George Washington University
- Charlotte Nelson
- Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco
- Viola D’Ambrosio
- London Tubular Centre, Department of Renal Medicine, University College London
- Chutong Zhong
- London Tubular Centre, Department of Renal Medicine, University College London
- Zhongwang Li
- London Tubular Centre, Department of Renal Medicine, University College London
- Alessandra Grillo
- London Tubular Centre, Department of Renal Medicine, University College London
- Elizabeth R. Wan
- London Tubular Centre, Department of Renal Medicine, University College London
- Vaksha Patel
- Department of Renal Medicine, University College London
- Eliah Overbey
- Institute for Computational Biomedicine, Weill Cornell Medical College
- JangKeun Kim
- Institute for Computational Biomedicine, Weill Cornell Medical College
- Sanghee Yun
- University of Pennsylvania Perelman School of Medicine
- Michael B. Vaughan
- School of Medicine, College of Medicine and Health, University College Cork
- Chris Cheshire
- Bioinformatics and Computational Biology Laboratory, The Francis Crick Institute
- Laura Cubitt
- Applied Biotechnology Laboratory, The Francis Crick Institute
- Jessica Broni-Tabi
- Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London
- Maneera Yousef Al-Jaber
- Anti-Doping Laboratory Qatar
- Valery Boyko
- Space Biosciences Division, NASA Ames Research Center
- Cem Meydan
- Institute for Computational Biomedicine, Weill Cornell Medical College
- Peter Barker
- MRC MDU Mouse Biochemistry Laboratory, University of Cambridge
- Shehbeel Arif
- Center for Data Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia
- Fatemeh Afsari
- Department of Medicine—Nephrology & Intelligent Critical Care Center, University of Florida
- Noah Allen
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute
- Mohammed Al-Maadheed
- Anti-Doping Laboratory Qatar
- Selin Altinok
- School of Medicine, The University of North Carolina at Chapel Hill
- Nourdine Bah
- Applied Biotechnology Laboratory, The Francis Crick Institute
- Samuel Border
- Department of Medicine—Nephrology & Intelligent Critical Care Center, University of Florida
- Amanda L. Brown
- Pharmacology, The University of North Carolina at Chapel Hill
- Keith Burling
- MRC MDU Mouse Biochemistry Laboratory, University of Cambridge
- Margareth Cheng-Campbell
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute
- Lorianna M. Colón
- Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia Research Institute
- Lovorka Degoricija
- KBR, Space Biosciences Division, NASA Ames Research Center
- Nichola Figg
- Department of Medicine, University of Cambridge
- Rebecca Finch
- School of Health, Science and Wellbeing, Staffordshire University
- Jonathan Foox
- Department of Physiology and Biophysics, Weill Cornell Medical College
- Pouya Faridi
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Alison French
- Space Biosciences Division, NASA Ames Research Center
- Samrawit Gebre
- Space Biosciences Division, NASA Ames Research Center
- Peter Gordon
- Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London
- Nadia Houerbi
- Physiology, Biophysics & Systems Biology, Weill Cornell Medical College
- Hossein Valipour Kahrood
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Frederico C. Kiffer
- Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia
- Aleksandra S. Klosinska
- Division of Experimental Medicine & Immunotherapeutics (EMIT), Department of Medicine, University of Cambridge
- Angela Kubik
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute
- Han-Chung Lee
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Yinghui Li
- State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center
- Nicholas Lucarelli
- Department of Medicine—Nephrology & Intelligent Critical Care Center, University of Florida
- Anthony L. Marullo
- School of Medicine, College of Medicine and Health, University College Cork
- Irina Matei
- Cornell Center for Immunology, Cornell University
- Colleen M. McCann
- Pharmacology, The University of North Carolina at Chapel Hill
- Sayat Mimar
- Department of Medicine—Nephrology & Intelligent Critical Care Center, University of Florida
- Ahmed Naglah
- Department of Medicine—Nephrology & Intelligent Critical Care Center, University of Florida
- Jérôme Nicod
- Advanced Sequencing Facility, The Francis Crick Institute
- Kevin M. O’Shaughnessy
- Division of Experimental Medicine & Immunotherapeutics (EMIT), Department of Medicine, University of Cambridge
- Lorraine Christine De Oliveira
- Blue Marble Space Institute of Science
- Leah Oswalt
- Pharmacology, The University of North Carolina at Chapel Hill
- Laura Ioana Patras
- Pediatrics, Weill Cornell Medical College
- San-huei Lai Polo
- KBR, Space Biosciences Division, NASA Ames Research Center
- María Rodríguez-Lopez
- Advanced Sequencing Facility, The Francis Crick Institute
- Candice Roufosse
- Department of Immunology and Inflammation, Imperial College London
- Omid Sadeghi-Alavijeh
- Department of Renal Medicine, University College London
- Rebekah Sanchez-Hodge
- Pharmacology, The University of North Carolina at Chapel Hill
- Anindya S. Paul
- Department of Medicine—Nephrology & Intelligent Critical Care Center, University of Florida
- Ralf Bernd Schittenhelm
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Annalise Schweickart
- Institute for Computational Biomedicine, Weill Cornell Medical College
- Ryan T. Scott
- KBR, Space Biosciences Division, NASA Ames Research Center
- Terry Chin Choy Lim Kam Sian
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Willian A. da Silveira
- School of Health, Science and Wellbeing, Staffordshire University
- Hubert Slawinski
- Advanced Sequencing Facility, The Francis Crick Institute
- Daniel Snell
- Advanced Sequencing Facility, The Francis Crick Institute
- Julio Sosa
- University Health Network
- Amanda M. Saravia-Butler
- KBR, Space Biosciences Division, NASA Ames Research Center
- Marshall Tabetah
- Department of Agricultural and Biological Engineering, Purdue University
- Erwin Tanuwidjaya
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Simon Walker-Samuel
- Centre for Advanced Biomedical Imaging, University College London
- Xiaoping Yang
- Proteomics, King’s College London
- Yasmin
- Division of Experimental Medicine & Immunotherapeutics (EMIT), Department of Medicine, University of Cambridge
- Haijian Zhang
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Jasminka Godovac-Zimmermann
- Department of Renal Medicine, University College London
- Pinaki Sarder
- Department of Medicine-Quantitative Health Section, University of Florida
- Lauren M. Sanders
- Space Biosciences Division, NASA Ames Research Center
- Sylvain V. Costes
- Space Biosciences Division, NASA Ames Research Center
- Robert A. A. Campbell
- Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London
- Fathi Karouia
- Blue Marble Space Institute of Science
- Vidya Mohamed-Alis
- Anti-Doping Laboratory Qatar
- Samuel Rodriques
- Applied Biotechnology Laboratory, The Francis Crick Institute
- Steven Lynham
- Proteomics, King’s College London
- Joel Ricky Steele
- Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University
- Sergio Baranzini
- Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco
- Hossein Fazelinia
- Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia Research Institute
- Zhongquan Dai
- State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center
- Akira Uruno
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai
- Dai Shiba
- Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA)
- Masayuki Yamamoto
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai
- Eduardo A.C.Almeida
- Space Biosciences Division, NASA Ames Research Center
- Elizabeth Blaber
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute
- Jonathan C. Schisler
- Pharmacology, The University of North Carolina at Chapel Hill
- Amelia J. Eisch
- Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia
- Masafumi Muratani
- Institute of Medicine, University of Tsukuba
- Sara R. Zwart
- Department of Preventative Medicine and Community Health, University of Texas Medical Branch
- Scott M. Smith
- NASA Johnson Space Center
- Jonathan M. Galazka
- Space Biosciences Division, NASA Ames Research Center
- Christopher E. Mason
- Department of Physiology and Biophysics, Weill Cornell Medical College
- Afshin Beheshti
- KBR, Space Biosciences Division, NASA Ames Research Center
- Stephen B. Walsh
- London Tubular Centre, Department of Renal Medicine, University College London
- DOI
- https://doi.org/10.1038/s41467-024-49212-1
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
