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