Impaired phosphorus conservation and 1,25 dihydroxyvitamin D generation during phosphorus deprivation in familial hypophosphatemic rickets.
The pathogenesis of familial hypophosphatemic rickets (FHR) is incompletely understood. We therefore examined the effects of acute dietary phosphorus deprivation to see whether renal phosphate conservation and increased 1,25 dihydroxyvitamin D [1,25(OH)2D] plasma levels, which normally follow restriction of phosphorus intake, could be induced in patients with FHR. Six healthy male volunteers (age 26 +/- 3 yr) and seven male patients with FHR (age 24 +/- 3 yr) were placed on a low phosphorus diet supplemented with aluminum hydroxide and studied over a 4-d period. The patients with FHR excreted more than five times as much phosphorus per day at the conclusion of the study than did the controls (176 +/- 61 mg/24 h vs. 33 +/- 11 mg/h). In the normal subjects, maximum tubular reabsorptive capacity for phosphorus/glomerular filtration rate (TmP/GFR) rose progressively during phosphorus deprivation, and the rise from base line was more than two times greater than that seen in patients with FHR. Immunoreactive parathyroid hormone levels and nephrogenous cyclic AMP were initially normal in both groups and no change was seen in either group with phosphorus deprivation. In the normal subjects, 1,25(OH)2D levels rose progressively over the 96 h of the study (49 +/- 3 to 63 +/- 6 pg/ml, P less than 0.05), while mean circulating 1,25(OH)2D in the patients with FHR did not change (34 +/- 3 to 29 +/- 3 pg/ml). The changes in individual plasma 1,25(OH)2D levels correlated strongly with the change in individual nephrogenous cyclic AMP measurements in the patients with FHR (r = +0.93), while no such correlation was observed in the normal subjects. These data demonstrate a defective renal response to phosphorus deprivation in patients with FHR including a qualitatively abnormal response in 1,25(OH)2D generation.
D000042:Absorption; D000328:Adult; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004032:Diet; D005919:Glomerular Filtration Rate; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000150:complications* / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000172:deficiency / Q000378:metabolism*; D012279:Rickets / Q000209:etiology*
D010281:Parathyroid Hormone; D010758:Phosphorus; D000242:Cyclic AMP; D002117:Calcitriol; D002118:Calcium