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

Abstract

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.

The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment

“…Urinary AQP2 excretion was measured in urine samples by ELISA as previously described . Briefly, urine samples were spun at 600 × g for 10 min.…”

Localization and function of the renal calcium-sensing receptor

“…However, when acidification is prevented by targeted gene ablation of the collecting duct-specific B1 subunit of the renal H + -ATPase in TRPV5 -/-mice significant tubular precipitation of calcium phosphase crystals was observed and animals died prematurely of hydronephrosis likely due to the presence of renal stones. In the collecting duct principal cells CaSR is localized on the apical membrane and co-localized with AQP2 in intracellular vesicles 12,56,57 where several lines of evidence from in vitro studies, from animal models in vivo and from observations in humans suggest that CaSR signaling inhibits vasopressin-induced trafficking and expression of the aquaporin-2 (AQP2) water channel [58][59][60][61][62][63][64][65][66] . The postulated mechanism implies that, under vasopressin action promoting water reabsorption from the lumen, an increase in urinary Ca concentration, due to urine concentration, activates the CaSR located on the apical membrane of collecting duct principal cells.…”

Regulation of urinary calcium excretion by vasopressin

“…The baseline level of calcium daily excretion is >300 mg/24 h, which is above the reported thresholds for hypercalciuria (270 mg/day for males and 250 mg/day for females). The relation between AVP and calcium excretion is particularly intriguing given that both are altered with ageing [ 24 ] and microgravity/bed rest [ 25 ].…”