Kidney Stone Risk during Microgravity and Long-Term Bed Rest: Role of Hypercalciuria and Aquaporins

Background: Exposure to microgravity results in alterations of renal function, uid redistribution and bone loss which contributes to the potential risk of renal stone formation. Hypercalciuria is recognized as a condition predisposing to calcium nephrolitiasis and long-term space ights cause bone loss coupled to a rise of urinary calcium excretion. Methods: AQP2 excretion was measured by ELISA in urines collected from healthy volunteers participating at the studies. Results: 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 analyze alteration of renal water handling during microgravity, we evaluated two ground-based analog of space ight, thermoneutral water immersion and bed rest. AQP2 excretion and diuresis were measured in two separated studies mimicking acute adaptation (6 hours water immersion) or chronic adaptation (35 days bed rest) to microgravity. Water immersion resulted in a signi cant increase in urinary output apparently not related to AQP2 alteration and manly due to reduced vasopressin secretion. On the other hand 35 days bed rest resulted in an increase in urinary calcium, which coincided with a signi cant decrease in AQP2 excretion (645±7.4 fmol/ml to 569±10.3 fmol/ml), which is expected to result in urine dilution reducing the risk of calcium saturation. Conclusions: Our data indicate that calciuria and water balance have to be strictly controlled during microgravity and long-term bed rest as key elements for the risk of kidney stone formation.