Rat models of normocalcemic hypercalciuria of different pathogenic mechanisms

Hypercalciuria was induced in female Sprague-Dawley rats, aged 40+/-2 days, by 7-day administration (mean+/-SEM) of calcitriol (5.4+/-0.1 ng/100 g per day, intraperitoneal), furosemide (14.9+/-1.9 mg/100 g per day, oral), or ammonium chloride (3.8+/-0.1 mEq/100 g per day, oral). Calciuria increased from 1.9+/-0.2, 1.6+/-0.2, and 1.9+/-0.3 to 5.4+/-0.5, 4.0+/-0.9, and 5.4+/-0.5 mg/100 g per day in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC, n = 10) groups, respectively. Calciuria did not change (1.9+/-0.3 vs. 1.6+/-0.1 mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats became hypercalciuric as assessed by urine calcium excretion above the 90th percentile of normal values. Hypercalciuria was of similar degree in the three groups of rats and was not associated with hypercalcemia, metabolic acidosis, severe serum electrolyte imbalance, or growth impairment. VD rats had low serum parathyroid hormone (PTH) concentrations (3.0+/-0.5 pg/ml vs. 15.8+/-1.3 pg/ml in controls, P