Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency.

Chronic renal insufficiency is associated with ebe- vated serum parathyroid hormone (PTH) levels (2#{176}HPT), de- ficiency of 1,25-dihydroxyvitamin D (l,25(OH)2D), and hy- pocalciuria. In chronic renal insufficiency, the 2#{176}HPT may result from reduced expression of the parathyroid gland extra- cellular Ca2tsensing receptor (CaSR). Since the CaSR was cloned from rat and human kidney, this study examined in rats whether expression of the renal CaSR is altered in experimen- tab chronic renal insufficiency. Four weeks after chronic renal insufficiency was induced by 5/6 nephrectomy (Nx) in Sprague Dawley rats, the serum creatinine concentration was 0.96 ± 0.06 mg/db compared with 0.35 ± 0.02 mg/dl in sham-operated animals (P < 0.05). The serum total Ca2� and phosphorus concentrations were not different. In the Nx group, the serum concentration of aniino-PTH was higher (65 ± 8 pg/ml), and the concentration of 1 ,25(OH)2D was significantly lower (47 ± 5 pg/mb) compared with 45 ± 5 pg/mb and 6 1 ± 4 pg/mb (P = 0.05) in the sham group, respectively. In a subset of rats studied, the Nx group was hypocalciuric (1 .4 ± 0.5 mg/kg per d) compared with the sham group (3.7 ± 0.5 mg/kg per d) (P < 0.05). In the Nx rats, CaSR mRNA expression and CaSR protein levels were found to be reduced by 35 and 38%, respectively, than those observed in controls. These results suggest that reduced renal CaSR expression in chronic renal insufficiency may play a role in disordered mineral ion ho- meostasis, including hypocalciuria.