Impact of Simulated Microgravity on Human Kidney Function: Identification of Early Biomarkers and Orthostatic Intolerance during Bedrest

Background: Astronauts have been reported to have an unusually high rate of kidney stone formation during spaceflight, which represents a risk for the heath and for the space mission success. Studies in humans adapted to actual or simulated microgravity (bedrest) demonstrate that exposure to microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion thus increasing the risk of renal stone formation. However, high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. Methods: Ten young healthy, were enrolled in the study. Each subject was evaluated before and after 10 days of strict horizontal bedrest and during bedrest no deviations from the lying position was allowed. Orthostatic blood pressure was measured during supine to stand test immediately after waking up after 10 days of bedrest. For each subject, blood and spot urine samples were taken every day and urinary excretion of AQP2 was quantified by ELISA. Other biomarkers were measured in the urine or in blood. Results: 10 days of immobilization was associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. A significant increase in adrenomedullin, a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity postbedrest. Conclusion: We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity. Funding: Government Support – Non-U.S.