IMPAIRMENT OF AQP2 TARGETING IN RESPONSE TO VASOPRESSIN IN HYPERCALCI- URIC PATIENTS: EVIDENCE FOR EXTRACELLULAR CALCIUM ACTING AS FIRST MESSENGER

Disturbances in renal concentrating ability have been associated with hypercalciuria in humans and experimental animals. In a previous work we have shown that extracellular calcium, possibly acting through Calcium Sensing Receptor (CaR) signaling, antagonizes forskolin-induced AQP2 translocation in renal cells. To test the hypothesis that increased urinary calcium inhibits AQP2 targeting in response to vasopressin in humans, in this study we evaluated AQP2 excretion in hypercalciuric children after 1-deamino-arginin-vasopressin (dDAVP) administration. Normocal- ciuric children served as control. Urine osmolarity and AQP2 excretion were measured in urine samples obtained hourly after 10 mg (if weight 0.2 on 3 separate samples. AQP2 excretion in urine samples was measured by Enzyme-Linked immunosorbent assay (ELISA). In the group of normocalciuric children having normal urinary concentration ability, dDAVP ad- ministration resulted in a significant increase in urine osmolality (1110±32 mOsm/l at peak, n=19) associated with a significant increase in urinary AQP2 excretion (from 250±80 fmol/mg Creat be- fore to 467±113 after dDAVP treatment, P