Oral calcium carbonate administration ameliorates the progression of renal failure in rats with hypertension

Abstract

Oral calcium supplementation is reported to have phosphate-binding and antihypertensive effects. Since both phosphate binders and antihypertensive agents are reported to attenuate renal injury, we studied the effect of oral calcium carbonate (CaCO 3) administration on the course of renal deterioration using doxorubicin-induced renal failure in rats treated with deoxycorticosterone acetate and salt for 10 weeks. Rats were divided into four groups: the CaCO 3 (6.0 g/kg/d) group (n = 12), the aluminum hydroxide (Al(OH) 3; 6.0 g/kg/d) group (n = 11, as a phosphate-binder control), the hydralazine (10 mg/kg/d) group (n = 11, as an antihypertensive control), and the control group (n = 12). All agents were given as a mixed chow diet. Blood pressure and urinary protein excretion progressively increased in the control rats. CaCO 3 and hydralazine lowered blood pressure, but Al(OH) 3 did not (185 ± 4 mm Hg, control; 160 ± 5 mm Hg, CaCO 3; 171 ± 8 mm Hg, Al(OH) 3; 156 ± 5 mm Hg, hydralazine at week 10). Proteinuria was reduced in the rats treated with CaCO 3 and Al(OH) 3 compared with those without the treatment (986 ± 86 mg/d, control; 551 ± 54 mg/d, CaCO 3; 527 ± 31 mg/d, Al(OH) 3; and 955 ± 68 mg/d, hydralazine at week 10). Serum phosphate concentration and calcium phosphate products also were significantly lower in both the CaCO 3 and Al(OH) 3 groups than in the control group. At week 10, increased serum urea nitrogen, impaired renal function, and glomerular sclerosis present in the control group were significantly attenuated in both in the CaCO 3 and Al(OH) 3 groups. No significant attenuation was observed in the hydralazine group in spite of lower blood pressure. We conclude that oral CaCO 3 administration attenuates the progression of renal failure associated with hypertension. This effect appears to be primarily related to its effects on divalent mineral metabolism and not on blood pressure.