Skeletal resistance to the calcemic action of parathyroid hormone in uremia: Role of 1,25(OH)2D3

Skeletal resistance to the calcemic action of PTH in uremia: Role of 1,25(OH) 2 D 3 . Studies were carried out to investigate the role of 1,25 dihydroxy vitamin D [1,25(OH) 2 D 3 ] in the skeletal resistance to the calcemic action of parathyroid hormone. The change in serum calcium after the intravenous infusion of 2 U of parathyroid extract (PTE)/kg body wt/hr for eight hours was evaluated in thyroparathyroidectomized (T-PTX) dogs before, and one, two and three days after, induction of uremia by bilateral ureteral ligation (11 dogs) or by bilateral nephrectomy (8 dogs). In another six nephrectomized and T-PTX dogs, 0.68 µg of 1,25(OH) 2 D 3 /day was given on the day of nephrectomy and for two days thereafter. Serum creatinine in each day of the study was not different among the three groups. The study also included the evaluation of the effect of sham operation (five dogs) and the administration of 1,25(OH) 2 D 3 to dogs with normal renal function (four dogs) on the calcemic response to PTE, as well as the reproducibility of such a response in the same animal. The results showed that 1) the calcemie response to PTE was markedly impaired after one day of bilateral ureteral ligation or nephrectomy, but the impairment was more severe after nephrectomy; 2) the calcemic response to PTE after two or three days of bilateral ureteral ligation was similar to that seen at one day after nephrectomy; 3) 1,25(OH) 2 D 3 partially restored the calcemic response to PTE in the nephrectomized animals to levels similar to those seen after one day of bilateral ureteral ligation; 4) sham operation did not affect the response to PTE, and repeated infusion of PTE produced similar changes in the concentrations of serum calcium. The data indicate that (a) a deficiency of 1,25(OH) 2 D 3 is at least partly responsible for the skeletal resistance to the calcemic action of PTH in uremia; (b) uremia, per se, may also contribute to this phenomenon; and (c) the kidney after one day of complete bilateral ureteral ligation may still produce 1,25(OH) 2 D 3 , but this ability is compromised after two days of ureteral obstruction. Resistance de l'os a l'action hypercalcemiante de la PTH au cours de l'uremie: Role du 1,25(OH) 2 D 3 . Ce travail a pour but d'etudier le role de la 1,25 dihydroxy vitamine D (1,25(OH) 2 D 3 ) dans la resistance de Tos a l'action hypercalcemiante de l'hormone parathyroidienne. Les modifications du calcium du plasma apres la perfusion intra-veineuse de 2 U d'extrait parathyroidien (PTE)/kg de poids corporel/heure pendant 8 heures ont ete mesurees chez des chiens thyroparathyroidectomises (T-PTX) avant puis 1,2 et 3 jours apres, l'induction de l'uremie par ligature bilaterale des ureteres (11 chiens) ou nephzectomie bilaterale (8 chiens). A un autre groupe de 6 chiens nephrectomises et T-PTX, 0,68 µg de 1,25(OH) 2 D 3 ont ete administres le jour de la nephrectomie et les deux jours suivants. La creatinine plasmatique a chaque jour de l'etude etait le meme dans les trois groupes. Le travail a aussi evalue les effets d'un simulacre d'operation (5 chiens) et de l'administration de 1,25(OH) 2 D 3 a des chiens ayant une fonction renale normale (4 chiens) sur la reponse de la calcemie au PTE ainsi que la reproductibilite de la reponse chez le meme animal. Les resultats montrent que: 1) la reponse calcemique au PTE est alteree de facon importante 24 heures apres la ligature ureterale ou la nephrectomie, l'alteration est plus grande apres nephrectomie; 2) la reponse calcemique au PTE apres deux et trois jours de ligature ureterale est semblable a celle observee apres un jour de nephrectomie; 3) le 1,25(OH) 2 D 3 restaure partiellement la reponse calcemique au PTE chez les animaux nephrectomises, la reponse obtenue est semblable a celle observee apres un jour de ligature ureterale bilaterale; 4) le simulacre d'operation n'affecte pas la reponse au PTE et les perfusions repetees de PTE produisent des modifications similaires de la concentration plasmatique de calcium. Ces resultats sont compatibles avec les interpretations suivantes: a) un deficit de 1,25(OH) 2 D 3 est, au moins en partie, responsable de la resistance osseuse a l'action hypercalcemiante de la PTH au cours de l'uremie, b) l'uremie, par elle-meme, peut aussi contribuer a cette modification et c) le rein peut encore produire du 1,25(OH) 2 D 3 apres un jour de ligature ureterale bilaterale mais cette capacite est abolie apres deux jours d'obstruction ureterale.