Selective modulation by vitamin D of renal response to parathyroid hormone: a study in calcitriol-resistant rickets.
Calcitriol-resistant rickets (CRR) is an autosomal recessive disease caused by mutated nonfunctioning vitamin D receptors. Because of their lack of biological activity of vitamin D, CRR patients were studied to investigate whether vitamin D modulates the effects of PTH on renal tubules. Five patients with CRR and three controls were studied. After normalization of serum calcium, phosphorus, and PTH levels by oral and i.v. administration of calcium, exogenous PTH-(1-34) was infused, and timed fractions of urine were collected for measurements of cAMP, sodium, potassium, phosphorus, calcium, and bicarbonate. Serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was measured before and after PTH-(1-34) infusion. Urinary cAMP and fractional excretion of potassium, phosphorus, and bicarbonate were similar in CRR patients and controls, as was the rise in the serum 1,25-(OH)2D3 concentration after PTH-(1-34) infusion. However, urinary excretion of calcium and sodium decreased after PTH-(1-34) infusion in controls, but not in CRR patients. These results suggest a selective modulation by vitamin D of the renal response to PTH; 1,25-(OH)2D3 facilitates PTH-induced calcium and sodium reabsorption, but does not influence PTH-induced cAMP excretion; phosphorus, potassium, and bicarbonate tubular transport, or 1 alpha-hydroxylation of 25-hydroxyvitamin D3.
Even
L
L
Department of Pediatrics, Bnai-Zion Medical Center, Haifa, Israel.
Weisman
Y
Y
Goldray
D
D
Hochberg
Z
Z
D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000652:urine; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D012279:Rickets / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D014807:Vitamin D / Q000494:pharmacology*
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); D014807:Vitamin D; D000242:Cyclic AMP; D002117:Calcitriol; D002118:Calcium