Daily but not pulse calcitriol therapy improves growth in experimental uremia

Calcitriol (C) pulse therapy is widely used to suppress secondary renal hyp erparathyroidism. However, high C serum concentrations may have an antiprol iferative effect on growth cartilage cells and may suppress growth rate. Th e study was designed to evaluate whether daily C and pulse C therapy have d ifferential effects an growth in uremic rats. Female Sprague-Dawley rats (1 50 g, n=5-10 per group) underwent two-stage subtotal nephrectomy (U). The d uration of uremia was 14-18 days. The animals were fed a standard diet or a diet with a low-calcium content. Rats on a low-calcium diet were randomize d for recombinant human growth hormone (rhGH) treatment (2.5 IU/kg per day) or solvent. C was injected subcutaneous twice daily (15 pmol/day) or intra peritoneal (105 pmol) twice per week. Weight gain and length gain was deter mined weekly. After sacrifice, total body calcium was determined by total b ody neutron activation analysis. Bone micromorphometric analysis of third l umbar vertebra and double staining with tetracycline for determination of m ineralization rate were performed. Whereas daily C significantly increased total body length gain within 2 weeks, pulse C did not (U solvent 4.0+/-0.3 cm, UC bolus 4.3+/-0.4 cm, UC daily 5.3+/-0.3 cm, P<0.05). A low-calcium d iet reduced and rhGH increased basal length gain and weight gain; regardles s of these preconditions, daily but not bolus C increased length gain signi ficantly. C both daily and in bolus form reduced bone osteoid content, but daily C improved mineral apposition rate more than C bolus. Total body calc ium corrected for body weight decreased with a low-calcium diet, was lowest with concomitant rhGH treatment, and was not improved by C. In conclusion, daily but not bolus C treatment improves growth in uremic rats.