Inhibition of calbindin D28K expression by cyclosporin a in rat kidney:: The possible pathogenesis of cyclosporin A-induced hypercalciuria

A recent study by Steiner et al. (Biochem Pharmacol 51: 253-258, 1996) demonstrated a decreased calbindin D-28K expression in the kidneys of cyclosporin A (CsA)-treated rats. To evaluate the association of renal calcium handling with calbindin D-28K expression in CsA-treated rats, two separate experiments (vehicle [VH] versus CsA groups, 1,25-dihydroxyvitamin D-3 [VitD] versus VitD + CsA groups) were done simultaneously. CsA (25 mg/kg per d, subcutaneously) and VitD (0.5 mu g/kg per d, subcutaneously) were given for 7 d. The CsA group showed decreased serum calcium, increased urine calcium excretion, and decreased calbindin D-28K protein level and immunoreactivity compared with the VH group. The VitD + CsA treatment decreased serum calcium, increased urine calcium excretion, and decreased calbindin D-28K protein level and immunoreactivity compared with the VitD alone. CsA treatment did not affect the serum parathyroid hormone and VitD levels. This study demonstrates an association of calbindin D-28K expression with the urinary calcium excretion in CsA-treated rats, and suggests that decreased calbindin D-28K expression may play a role in renal calcium wasting.