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; [No Value] 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

doi:10.1038/s41467-024-49212-1

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 BarkerShehbeel 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, [No Value] 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

Proteomics

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Article number	4923
Pages (from-to)	4923
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-49212-1
Publication status	Published - 11 Jun 2024

Keywords

Animals
Space Flight
Humans
Mice
Cosmic Radiation/adverse effects
Rats
Male
Kidney/pathology
Kidney Diseases/pathology
Weightlessness/adverse effects
Astronauts
Mice, Inbred C57BL
Proteomics
Female
Mars
Weightlessness Simulation/adverse effects

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-024-49212-1Licence: CC BY

Cite this

Siew, K., Nestler, K. A., Nelson, C., D'Ambrosio, V., Zhong, C., Li, Z., Grillo, A., Wan, E. R., Patel, V., Overbey, E., Kim, J., Yun, S., Vaughan, M. B., Cheshire, C., Cubitt, L., Broni-Tabi, J., Al-Jaber, M. Y., Boyko, V., Meydan, C., ... Walsh, S. B. (2024). Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction. Nature Communications, 15(1), 4923. Article 4923. https://doi.org/10.1038/s41467-024-49212-1

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

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.",

keywords = "Animals, Space Flight, Humans, Mice, Cosmic Radiation/adverse effects, Rats, Male, Kidney/pathology, Kidney Diseases/pathology, Weightlessness/adverse effects, Astronauts, Mice, Inbred C57BL, Proteomics, Female, Mars, Weightlessness Simulation/adverse effects",

author = "Keith Siew and Nestler, {Kevin A} and Charlotte Nelson and Viola D'Ambrosio and Chutong Zhong and Zhongwang Li and Alessandra Grillo and Wan, {Elizabeth R} and Vaksha Patel and Eliah Overbey and JangKeun Kim and Sanghee Yun and Vaughan, {Michael B} and Chris Cheshire and Laura Cubitt and Jessica Broni-Tabi and Al-Jaber, {Maneera Yousef} and Valery Boyko and Cem Meydan and Peter Barker and Shehbeel Arif and Fatemeh Afsari and Noah Allen and Mohammed Al-Maadheed and Selin Altinok and Nourdine Bah and Samuel Border and Brown, {Amanda L} and Keith Burling and Margareth Cheng-Campbell and Col{\'o}n, {Lorianna M} and Lovorka Degoricija and Nichola Figg and Rebecca Finch and Jonathan Foox and Pouya Faridi and Alison French and Samrawit Gebre and Peter Gordon and Nadia Houerbi and {Valipour Kahrood}, Hossein and Kiffer, {Frederico C} and Klosinska, {Aleksandra S} and Angela Kubik and Han-Chung Lee and Yinghui Li and Nicholas Lucarelli and Marullo, {Anthony L} and Irina Matei and McCann, {Colleen M} and Sayat Mimar and Ahmed Naglah and J{\'e}r{\^o}me Nicod and O'Shaughnessy, {Kevin M} and Oliveira, {Lorraine Christine De} and Leah Oswalt and Patras, {Laura Ioana} and {Lai Polo}, San-Huei and Mar{\'i}a Rodr{\'i}guez-Lopez and Candice Roufosse and Omid Sadeghi-Alavijeh and Rebekah Sanchez-Hodge and Paul, {Anindya S} and Schittenhelm, {Ralf Bernd} and Annalise Schweickart and Scott, {Ryan T} and {Choy Lim Kam Sian}, {Terry Chin} and {da Silveira}, {Willian A} and Hubert Slawinski and Daniel Snell and Julio Sosa and Saravia-Butler, {Amanda M} and Marshall Tabetah and Erwin Tanuwidjaya and Simon Walker-Samuel and Xiaoping Yang and Yasmin, {[No Value]} and Haijian Zhang and Jasminka Godovac-Zimmermann and Pinaki Sarder and Sanders, {Lauren M} and Costes, {Sylvain V} and Campbell, {Robert A A} and Fathi Karouia and Vidya Mohamed-Alis and Samuel Rodriques and Steven Lynham and Steele, {Joel Ricky} and Sergio Baranzini and Hossein Fazelinia and Zhongquan Dai and Akira Uruno and Dai Shiba and Masayuki Yamamoto and {A C Almeida}, Eduardo and Elizabeth Blaber and Schisler, {Jonathan C} and Eisch, {Amelia J} and Masafumi Muratani and Zwart, {Sara R} and Smith, {Scott M} and Galazka, {Jonathan M} and Mason, {Christopher E} and Afshin Beheshti and Walsh, {Stephen B}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jun,

day = "11",

doi = "10.1038/s41467-024-49212-1",

language = "English",

volume = "15",

pages = "4923",

journal = "Nature Communications",

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Siew, K, Nestler, KA, Nelson, C, D'Ambrosio, V, Zhong, C, Li, Z, Grillo, A, Wan, ER, Patel, V, Overbey, E, Kim, J, Yun, S, Vaughan, MB, Cheshire, C, Cubitt, L, Broni-Tabi, J, Al-Jaber, MY, Boyko, V, Meydan, C, Barker, P, Arif, S, Afsari, F, Allen, N, Al-Maadheed, M, Altinok, S, Bah, N, Border, S, Brown, AL, Burling, K, Cheng-Campbell, M, Colón, LM, Degoricija, L, Figg, N, Finch, R, Foox, J, Faridi, P, French, A, Gebre, S, Gordon, P, Houerbi, N, Valipour Kahrood, H, Kiffer, FC, Klosinska, AS, Kubik, A, Lee, H-C, Li, Y, Lucarelli, N, Marullo, AL, Matei, I, McCann, CM, Mimar, S, Naglah, A, Nicod, J, O'Shaughnessy, KM, Oliveira, LCD, Oswalt, L, Patras, LI, Lai Polo, S-H, Rodríguez-Lopez, M, Roufosse, C, Sadeghi-Alavijeh, O, Sanchez-Hodge, R, Paul, AS, Schittenhelm, RB, Schweickart, A, Scott, RT, Choy Lim Kam Sian, TC, da Silveira, WA, Slawinski, H, Snell, D, Sosa, J, Saravia-Butler, AM, Tabetah, M, Tanuwidjaya, E, Walker-Samuel, S, Yang, X, Yasmin, NV, Zhang, H, Godovac-Zimmermann, J, Sarder, P, Sanders, LM, Costes, SV, Campbell, RAA, Karouia, F, Mohamed-Alis, V, Rodriques, S, Lynham, S, Steele, JR, Baranzini, S, Fazelinia, H, Dai, Z, Uruno, A, Shiba, D, Yamamoto, M, A C Almeida, E, Blaber, E, Schisler, JC, Eisch, AJ, Muratani, M, Zwart, SR, Smith, SM, Galazka, JM, Mason, CE, Beheshti, A & Walsh, SB 2024, 'Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction', Nature Communications, vol. 15, no. 1, 4923, pp. 4923. https://doi.org/10.1038/s41467-024-49212-1

TY - JOUR

T1 - Cosmic kidney disease

T2 - an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

AU - Siew, Keith

AU - Nestler, Kevin A

AU - Nelson, Charlotte

AU - D'Ambrosio, Viola

AU - Zhong, Chutong

AU - Li, Zhongwang

AU - Grillo, Alessandra

AU - Wan, Elizabeth R

AU - Patel, Vaksha

AU - Overbey, Eliah

AU - Kim, JangKeun

AU - Yun, Sanghee

AU - Vaughan, Michael B

AU - Cheshire, Chris

AU - Cubitt, Laura

AU - Broni-Tabi, Jessica

AU - Al-Jaber, Maneera Yousef

AU - Boyko, Valery

AU - Meydan, Cem

AU - Barker, Peter

AU - Arif, Shehbeel

AU - Afsari, Fatemeh

AU - Allen, Noah

AU - Al-Maadheed, Mohammed

AU - Altinok, Selin

AU - Bah, Nourdine

AU - Border, Samuel

AU - Brown, Amanda L

AU - Burling, Keith

AU - Cheng-Campbell, Margareth

AU - Colón, Lorianna M

AU - Degoricija, Lovorka

AU - Figg, Nichola

AU - Finch, Rebecca

AU - Foox, Jonathan

AU - Faridi, Pouya

AU - French, Alison

AU - Gebre, Samrawit

AU - Gordon, Peter

AU - Houerbi, Nadia

AU - Valipour Kahrood, Hossein

AU - Kiffer, Frederico C

AU - Klosinska, Aleksandra S

AU - Kubik, Angela

AU - Lee, Han-Chung

AU - Li, Yinghui

AU - Lucarelli, Nicholas

AU - Marullo, Anthony L

AU - Matei, Irina

AU - McCann, Colleen M

AU - Mimar, Sayat

AU - Naglah, Ahmed

AU - Nicod, Jérôme

AU - O'Shaughnessy, Kevin M

AU - Oliveira, Lorraine Christine De

AU - Oswalt, Leah

AU - Patras, Laura Ioana

AU - Lai Polo, San-Huei

AU - Rodríguez-Lopez, María

AU - Roufosse, Candice

AU - Sadeghi-Alavijeh, Omid

AU - Sanchez-Hodge, Rebekah

AU - Paul, Anindya S

AU - Schittenhelm, Ralf Bernd

AU - Schweickart, Annalise

AU - Scott, Ryan T

AU - Choy Lim Kam Sian, Terry Chin

AU - da Silveira, Willian A

AU - Slawinski, Hubert

AU - Snell, Daniel

AU - Sosa, Julio

AU - Saravia-Butler, Amanda M

AU - Tabetah, Marshall

AU - Tanuwidjaya, Erwin

AU - Walker-Samuel, Simon

AU - Yang, Xiaoping

AU - Yasmin, [No Value]

AU - Zhang, Haijian

AU - Godovac-Zimmermann, Jasminka

AU - Sarder, Pinaki

AU - Sanders, Lauren M

AU - Costes, Sylvain V

AU - Campbell, Robert A A

AU - Karouia, Fathi

AU - Mohamed-Alis, Vidya

AU - Rodriques, Samuel

AU - Lynham, Steven

AU - Steele, Joel Ricky

AU - Baranzini, Sergio

AU - Fazelinia, Hossein

AU - Dai, Zhongquan

AU - Uruno, Akira

AU - Shiba, Dai

AU - Yamamoto, Masayuki

AU - A C Almeida, Eduardo

AU - Blaber, Elizabeth

AU - Schisler, Jonathan C

AU - Eisch, Amelia J

AU - Muratani, Masafumi

AU - Zwart, Sara R

AU - Smith, Scott M

AU - Galazka, Jonathan M

AU - Mason, Christopher E

AU - Beheshti, Afshin

AU - Walsh, Stephen B

PY - 2024/6/11

Y1 - 2024/6/11

N2 - 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.

AB - 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.

KW - Animals

KW - Space Flight

KW - Humans

KW - Mice

KW - Cosmic Radiation/adverse effects

KW - Rats

KW - Male

KW - Kidney/pathology

KW - Kidney Diseases/pathology

KW - Weightlessness/adverse effects

KW - Astronauts

KW - Mice, Inbred C57BL

KW - Proteomics

KW - Female

KW - Mars

KW - Weightlessness Simulation/adverse effects

UR - http://www.scopus.com/inward/record.url?scp=85195888276&partnerID=8YFLogxK

U2 - 10.1038/s41467-024-49212-1

DO - 10.1038/s41467-024-49212-1

M3 - Article

C2 - 38862484

SN - 2041-1723

VL - 15

SP - 4923

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4923

ER -

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

Abstract

Keywords

UN SDGs

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