Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction
Authors: 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 , Patras Laura Ioana , Lai Polo San-huei , Rodríguez-Lopez María , Roufosse Candice , Sadeghi-Alavijeh Omid , Sanchez-Hodge Rebekah , Paul Anindya S. , Schittenhelm Ralf Bernd , Schweickart Annalise , Scott Ryan T. , Choy Lim Kam Sian Terry Chin , da Silveira Willian A. , Slawinski Hubert , Snell Daniel , Sosa Julio , Saravia-Butler Amanda M. , Tabetah Marshall , Tanuwidjaya Erwin , Walker-Samuel Simon , Yang Xiaoping , Yasmin  , Zhang Haijian , Godovac-Zimmermann Jasminka , Sarder Pinaki , Sanders Lauren M. , Costes Sylvain V. , Campbell Robert A. A. , Karouia Fathi , Mohamed-Alis Vidya , Rodriques Samuel , Lynham Steven , Steele Joel Ricky , Baranzini Sergio , Fazelinia Hossein , Dai Zhongquan , Uruno Akira , Shiba Dai , Yamamoto Masayuki , A.C.Almeida Eduardo , Blaber Elizabeth , Schisler Jonathan C. , Eisch Amelia J. , Muratani Masafumi , Zwart Sara R. , Smith Scott M. , Galazka Jonathan M. , Mason Christopher E. , Beheshti Afshin , Walsh Stephen B. 
Published: June 2024

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.