Reversal of hyperparathyroidism in response to dietary phosphorus restriction in the uremic dog

Reversal of hyperparathyroidism in response to dietary phosphorus restriction in the uremic dog. The role of phosphorus in the genesis of uremic hyperparathyroidism is well established. Prophylactic reduction of dietary phosphorus intake (PRS-P) in exact proportion to GFR reduction prevents renal hyperparathyroidism, but its effects on established hyperparathyroidism, serum calcium and phosphate concentration, and phosphorus balance are not known. Seven chronically uremic dogs (2 to 5 months) were housed in metabolic cages and maintained on a controlled phosphorus intake of 1,200 mg/day. After a control period of 10 days, the dogs were subjected to PRS-P. Control GFR averaged 16 ± 4 ml/min; serum phosphate concentration (S P ), 4.3 ± 0.2 mg/dl; serum ionized calcium concentration (S ICa ), 4.67 ± 0.29 mg/dl; parathyroid hormone level (PTH), 610 ± 91 µl · Eq/ml; and 24-hr urine phosphate excretion (U PO 4 V), 845 ± 84 mg. During PRS-P, no change in GFR or S P occurred (17 ml/min and 4.3 mg/dl, respectively). S ICa increased significantly by day 2 and plateaued by day 4 at 5.13 ± 0.20 mg/dl. PTH fell progressively over the 16 days of PRS-P to 170 ± 49 µl · Eq/ml. U PO 4 V fell on day 1 of PRS-P and plateaued by day 2. Stool phosphorus excretion averaged 43% of intake. Total phosphorus excretion (urine plus stool) did not differ significantly from measured intake. Tubular maximum phosphate reabsorption/GFR averaged 2.7 ± 0.4 mg/100 ml before PRS-P and increased significantly to 4.9 ± 0.2 mg/100 ml after 18 days of PRS-P. In summary, dietary therapy with PRS-P appears to be an effective method, not only for preventing uremic hyperparathyroidism, but for reversing established uremic hyperparathyroidism. In view of the growing evidence that PTH may be a major "uremic toxin", PRS-P could represent an important element in the future therapy of chronic renal failure. Reversion de l'hyperparathyroicarondisme en reponse a la restriction alimentaire de phosphate chez le chien uremique. Le role du phosphore dans la genese de l'hyperparathyroicarondisme est bien etabli. La reduction prophylactique de l'apport alimentaire de phosphore (PRS-P) dans la meme proportion que celle du debit de filtration glomerulaire empeche l'hyperparathyroicaron;disme mais son effet sur l'hyperparathyroicaron;disme installe, sur les concentrations plasmatiques de calcium et de phosphore et sur le bilan de phosphore, ne sont pas connus. Sept chiens uremiques chroniques (2 a 5 mois) ont ete installes dans des cages metaboliques et maintenus a un apport de 1200 mg de phosphore/jour. Apres une periode controle de 10 jours les chiens ont ete soumis a PRS-P. Le debit de filtration glomerulaire pendant la periode controle etait de 16 ± 4 ml/min; le phosphate plasmatique (S P ) de 4,3 ± 0,2 mg/dl; le calcium ionise du plasma (S ICa ) de 4,67 ± 0,29 mg/dl; l'hormone parathyroĭdienne (PTH) de 610 ± 91 µl · Eq/ml; l'excretion urinaire quotidienne de phosphate (U PO 4 V) de 845 ± 84 mg. Pendant PRS-P GFR et S P n'ont pas ete modifies (17 ml/min et 4,3 mg/dl, respectivement). S ICa a augmente significativement a partir du 2eme jour pour atteindre un plateau au 4eme, a 5,13 ± 0,20 mg/dl. La PTH a diminue progressivement pendant les 16 jours de PRS-P jusqu'a 170 ± 49 µl · Eq/ml. U PO 4 V a diminue des le premier jour jusqu'au plateau atteint le 2eme jour. L'excretion fecale de phosphore a ete de 43% de l'apport. L'excretion totale de phosphore (urine et selles) n'etait pas significativement differente de l'apport mesure. La reabsorption tubulaire maximum de phosphate/GFR etait en moyenne de 2,7 ± 0,4 mg/100 ml avant PRS-P et a augmente significativement a 4,9 ± 0,2 mg/100 ml apres 18 jours. En resume, PRS-P parait une methode efficace non seulement pour empecher l'hyperparathyroicaron;disme mais aussi pour obtenir sa reversion. Du fait de l'accumulation des preuves que la PTH est une toxine uremique, PRS-P pourrait etre un element important dans le traitement futur de l'insuffisance renale chronique.