Vasopressin, Hypercalciuria and Aquaporin – The Key Elements for Impaired Renal Water Handling in Astronauts?

Drummer, C.; Valenti, Giovanna; Cirillo, Massimo; Perna, Alessandra F.; Bellini, Luigi; Nenov, Vesselin D.; Santo, Natale G. De

doi:10.1159/000064111

Cited by 11 publications

(6 citation statements)

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“…Immobilization or exposure to microgravity induce several alterations of renal function including fluid redistribution and bone loss causing increased calciuria and reduced plasma volume [9,10]. In this context, bed rest represents a valuable experimental model to mimic the effects of microgravity on earth [11].…”

Section: Introductionmentioning

confidence: 99%

A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria

et al. 2014

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BackgroundExposure to microgravity or immobilization results in alterations of renal function, fluid redistribution and bone loss, which couples to a rise of urinary calcium excretion. We recently demonstrated that high calcium delivery to the collecting duct reduces local Aquaporin-2 (AQP2) mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration and reducing calcium saturation. To investigate renal water balance adaptation during bed rest, a model to mimic the effects of microgravity on earth, the effect of changes in urinary calcium on urinary AQP2 excretion were assessed.MethodsTen healthy men (aged 21-28 years) participated in the experiment. Study design included 7 days of adaptation and 35 days of continuous bed rest (days -6 to 0 and 1 to 35, respectively) under controlled diet. Food records and 24-hour urine samples were collected daily from day -3 to 35. Changes in blood hematocrit were used as an indirect index of plasma volume changes. AQP2 excretion was measured by ELISA.ResultsBed rest induced bone demineralization and a transient increase in urinary calcium followed by transient decrease in AQP2 excretion, which can reduce the urine concentrating ability causing plasma volume reduction. The return of calciuria to baseline was followed by a recovery of AQP2 excretion, which allows for a partial restoration of plasma volume.ConclusionsThese results further support the view that urinary calcium can modulate the vasopressin-dependent urine concentration through a down-regulation of AQP2 expression/trafficking. This mechanism could have a key role in the prevention of urine super-saturation due to hypercalciuria.

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Section: Introductionmentioning

confidence: 99%

A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria

et al. 2014

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“…The biomarkers for renal function were tested either in the urine or in the blood collected daily during the bedrest. Immobilization or exposure to microgravity induces several alterations of renal function including fluid redistribution ( Drummer et al, 2002 ; Gaspare De Santo et al, 2005 ). It is known that vasopressin is the key hormone regulating water homeostasis.…”

Section: Resultsmentioning

confidence: 99%

“…Some alterations of renal function including fluid redistribution, bone loss induced hypercalciuria, renal stone risk, reduced plasma volume, secondary to immobilization or bedrest have been described ( Drummer et al, 2002 ; Gaspare De Santo et al, 2005 ; Cavalier et al, 2013 ; Smith et al, 2015 ). More specifically, in a previous study, we evaluated the effects of 35-day bedrest on changes in urinary calcium, modulation of the vasopressin-regulated water channel aquaporin-2, and blood hematocrit the latter used as an index of changes in plasma volume ( Tamma et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest

et al. 2022

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Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that 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. We report here that 10 days of inactivity are 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. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. 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.

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“…This phenomenon could be due to several known factors including 1) changes in hydrostatic pressure that drive the movement of water and protein from the intravascular space to intracellular and interstitial compartments resulting in hemodilution 23 or 2) a partial decoupling of the renin-angiotensin-aldosterone-vasopressin system due to hypercalciuria secondary to bone mineral loss on orbit. 24 Our team explored the hypothesis that microgravity-induced changes in PTEC-mediated metabolism of Vitamin D might also contribute to the observed decline in plasma levels of 1α,25(OH) 2 D 3 .…”

Section: Discussionmentioning

confidence: 99%

Impact of microgravity on a three-dimensional microphysiologic culture of the human kidney proximal tubule epithelium: cell response to serum and vitamin D

Kelly,

Lindberg,

Jones-Isaac

et al. 2023

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The microgravity environment aboard the International Space Station (ISS) provides a unique stressor that can help understand underlying cellular and molecular drivers of pathological changes observed in astronauts with the ultimate goals of developing strategies to enable long-term spaceflight and better treatment of diseases on Earth. We used this unique environment to evaluate the effects of microgravity on kidney proximal tubule epithelial cell (PTEC) response to serum exposure and vitamin D biotransformation capacity. To test if microgravity alters the pathologic response of the proximal tubule to serum exposure, we treated PTECs cultured in a microphysiological system (PT-MPS) with human serum and measured biomarkers of toxicity and inflammation (KIM-1 and IL-6) and conducted global transcriptomics via RNAseq on cells undergoing flight (microgravity) and respective controls (ground). We also treated 3D cultured PTECs with 25(OH)D3 (vitamin D) and monitored vitamin D metabolite formation, conducted global transcriptomics via RNAseq, and evaluated transcript expression of CYP27B1, CYP24A1, or CYP3A5 in PTECs undergoing flight (microgravity) and respective ground controls. We demonstrated that microgravity neither altered PTEC metabolism of vitamin D nor did it induce a unique response of PTECs to human serum, suggesting that these fundamental biochemical pathways in the kidney proximal tubule are not significantly altered by short-term exposure to microgravity. Given the prospect of extended spaceflight, more study is needed to determine if these responses are consistent with extended (> 6 month) exposure to microgravity.

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Vasopressin, Hypercalciuria and Aquaporin – The Key Elements for Impaired Renal Water Handling in Astronauts?

Cited by 11 publications

References 36 publications

A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria

A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria

Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest

Impact of microgravity on a three-dimensional microphysiologic culture of the human kidney proximal tubule epithelium: cell response to serum and vitamin D

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