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

Abstract

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.

Keywords: adrenomedullin; aquaporin-2 (AQP2); bedrest; calcium; copeptin; kidney; osteopontin; vasopressin.

FIGURE 1

(A) Serum Copeptin (% variation versus BDC1) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using One Sample t test (*p < 0.05 for BR5 vs. BDC1); (B) urinary AQP2 excretion normalized to Creatinuria (fmol/mg) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using Ordinary one-way Anova test (*p < 0.05 for BR5 and BR7 vs. BDC1; **p < 0.01 for BR8 vs. BDC1).

FIGURE 2

(A) Urinary Sodium excretion normalized to Creatinuria (mmol/mg) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using Ordinary one-way Anova test (*p < 0.05 for BR2 vs. BDC1); (B) urinary Potassium excretion normalized to Creatinuria (mmol/mg) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using Ordinary one-way Anova test (*p < 0.05 for BR2 vs. BDC1; **p < 0.01 for BR6 vs. BDC1).

FIGURE 3

Urinary Calcium excretion normalized to Creatinuria (mmol/mg) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using Ordinary one-way Anova test (*p < 0.05 for BR4 vs. BDC1; **p < 0.01 for BR5 vs. BDC1).

FIGURE 4

Serum PTH (pg/ml) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using Ordinary one-way Anova test (*p < 0.05 for BR3 vs. BDC1; **p < 0.01; for BR5, BR7, BR9, R+1 and R+2 vs. BDC1).

FIGURE 5

Urinary Osteopontin (OPN) excretion normalized to Creatinuria (ng/mg) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using Ordinary one-way Anova test (*p < 0.05 for BR1 vs. BDC1; **p < 0.01 for BR5 vs. BDC1; ***p < 0.001 for BR9 and R+2 vs. BDC1).

FIGURE 6

Serum Adrenomedullin (ADM) (% variation vs. BDC1) during 10-day bedrest. Data are expressed as mean ± S.E.M. Statistical analysis was done using One Sample t test (*p < 0.05 for BR5 vs. BDC1).