The prospect of long-duration deep space missions, such as a roundtrip voyage to Mars, has spurred intense research into the health effects of prolonged exposure to the unique conditions of spaceflight. While the musculoskeletal, neurological, ocular and cardiovascular impacts of microgravity have been a major focus, the effects on other vital organs like the kidneys have received less attention. A comprehensive new study led by researchers at University College London provides concerning evidence that the structure and function of the kidneys are significantly altered by spaceflight conditions, with galactic cosmic radiation potentially causing irreversible damage that could imperil the health of astronauts on extended missions beyond Earth’s protective magnetosphere.
Largest Study to Date on Kidney Health in Spaceflight
The UCL-led research team conducted the most extensive analysis of kidney health in spaceflight to date, integrating data from over 20 study cohorts across 40 institutions on five continents. This included physiological measurements and tissue samples from more than 40 human and animal missions in low Earth orbit, primarily to the International Space Station, as well as 11 ground-based simulations exposing mice and rats to spaceflight-like conditions. Notably, the study incorporated the first health data from the commercial SpaceX Inspiration4 mission in 2021.
By applying cutting-edge biomolecular techniques to these diverse datasets, the scientists were able to assess the impact of microgravity and space radiation on kidney structure and function at an unprecedented level of detail. The results paint a concerning picture of progressive renal damage and dysfunction that could have severe implications for the feasibility of long-duration deep space travel.
Spaceflight Induces Remodeling of Kidney Tubules
One of the key findings was that exposure to the microgravity environment of spaceflight causes the kidneys to undergo structural “remodeling” within a matter of weeks. Detailed imaging and morphometric analyses revealed that specific segments of the kidney tubules responsible for fine-tuning the reabsorption of critical electrolytes like calcium and sodium become significantly shrunken.
This tubular atrophy was particularly pronounced in the distal convoluted tubules, which play a central role in regulating mineral balance. Phosphoproteomic profiling showed a marked dephosphorylation of key sodium and chloride transporters in these segments, indicating an impairment in their ability to reabsorb these ions from the forming urine. These tubular changes were accompanied by a reduction in overall kidney size relative to body weight in the spaceflight-exposed animals.
The researchers propose that this rapid renal remodeling is likely an adaptation to the redistribution of bodily fluids that occurs upon entering microgravity. On Earth, gravity causes blood and other fluids to pool in the lower body. In the weightless environment of space, these fluids shift towards the head and upper body, reducing the pressure gradient that normally drives blood flow to the kidneys.
This hemodynamic change is thought to activate compensatory mechanisms aimed at enhancing sodium and water retention to maintain blood pressure and tissue perfusion. However, the study’s results suggest that these adaptations come at the cost of tubular atrophy and electrolyte dysregulation, which may contribute to the increased risk of kidney stones seen in astronauts.
Galactic Cosmic Radiation Causes Persistent Kidney Damage
While the renal remodeling induced by microgravity appears to be largely reversible upon returning to Earth, the study uncovered evidence that exposure to the heavy ion radiation of deep space may cause more permanent and progressive kidney damage. To simulate the effects of galactic cosmic radiation (GCR), mice were exposed to doses of ground-based ion beams equivalent to what would be experienced on a 1.5 to 2.5 year roundtrip mission to Mars.
Detailed histopathological examination of the animals’ kidney tissue 6 months after this simulated GCR exposure revealed signs of persistent inflammation, fibrosis, and tubular injury. Specific regions of the kidney appeared particularly vulnerable, with the proximal tubules and vascular bundles of the inner stripe of the outer medulla showing increased expression of damage markers and pro-inflammatory micro RNAs.
Accompanying these structural changes were indicators of impaired renal function, including elevated urinary protein levels and reduced reabsorption of glucose, amino acids, and magnesium. Multi-omic pathway analyses implicated mitochondrial dysfunction, oxidative stress, and senescence pathways as potential mediators of this radiation-induced nephropathy.
The researchers caution that these findings, while concerning, likely underestimate the extent of kidney damage that would occur during an actual Mars mission. The simulated radiation exposures were delivered in a single acute dose rather than the chronic, low-dose-rate exposures that would occur in deep space. Additionally, the experimental animals were exposed to GCR in isolation, without the concurrent fluid shifts and physiological stresses of microgravity that could compound the deleterious effects.
Implications for Long-Duration Space Missions
The study’s results underscore the vital importance of developing effective countermeasures to protect astronaut kidney health during extended voyages outside the Earth’s magnetosphere. While medications like potassium citrate are currently used to reduce the risk of kidney stones in spaceflight, the findings suggest that additional interventions targeting tubular remodeling and radiation-induced damage may be necessary for missions to Mars and beyond.
Potential strategies could include drugs that modulate the activity of renal sodium transporters, anti-fibrotic agents, and antioxidant supplements to mitigate oxidative stress. The authors also propose that artificial gravity systems, such as centrifuges, could help prevent the fluid shifts and hemodynamic changes that appear to drive the microgravity-induced tubular remodeling.
However, the development and validation of such countermeasures will require a concerted research effort and substantial investment. The study’s multi-omic analyses identified numerous molecular pathways and targets that could guide future studies aimed at unraveling the mechanisms of spaceflight-associated kidney injury and identifying druggable targets.
At the same time, the logistical and ethical challenges of conducting long-term studies on the effects of deep space radiation in humans remain formidable. While animal models and ground-based simulations offer valuable insights, they cannot fully recapitulate the complex interplay of stressors experienced during actual spaceflight. As a result, much of our understanding of the health risks of Mars missions may have to be inferred and extrapolated from incomplete data.
Summary
The landmark study led by the UCL team provides the most comprehensive picture to date of how the kidneys are affected by prolonged exposure to spaceflight conditions. By integrating physiological, morphological, and multi-omic data from an unprecedented range of human and animal spaceflight missions and simulations, the researchers have uncovered evidence of progressive renal damage and dysfunction that could jeopardize the health of astronauts on extended voyages to Mars and beyond.
The rapid remodeling of kidney tubules induced by microgravity, coupled with the persistent inflammation and fibrosis caused by heavy ion space radiation, paints a concerning picture of the challenges that will need to be overcome to ensure the safety of future deep space explorers. While the development of effective countermeasures will require substantial further research and investment, studies like this provide a vital foundation for understanding and ultimately mitigating the health risks of long-duration spaceflight.
