The influence of renal prostaglandins on urinary calcium excretion in idiopathic urolithiasis.
Hypercalciuria is well recognized as an important factor in the cause of idiopathic calcium stone disease. Identification of the exact mechanism for the renal tubular handling of calcium has proved elusive, hence, treatment methods to alter the concentration of urine calcium in hypercalciuric stone formers have hitherto been non-specific. It is now well established that renal prostaglandins influence intrarenal hemodynamics and tubular electrolyte excretion. As the renal handling of sodium and calcium is intimately related, the possibility that the mechanism underlying hypercalciuria may be prostaglandin mediated was considered. Experiments were performed in conscious Sprague-Dawley rats (n = 10) to determine the changes in calcium excretion following prostaglandin synthetase inhibition with indomethacin. Calcium excretion was significantly reduced (p less than 0.01), compared with control animals (n = 10). Further experiments were performed in anesthetized monkeys (Macaca fascicularis) to see if the inhibitory effect of indomethacin was reversible. Exogenous prostaglandin (PGE2) infusion resulted in a marked calciuretic response without producing changes in glomerular filtration rate or blood pressure. Forty-three hypercalciuric patients were treated with a prostaglandin inhibitor for periods ranging from 2 to 4 weeks, and all showed a significant fall in urinary calcium excretion to within the normal range. This clinical and experimental study suggests that prostaglandin (PGE2) is a hormone which determines the renal handling of calcium by influencing renal tubular function.
D000818:Animals; D002118:Calcium / Q000652:urine*; D015232:Dinoprostone; D005480:Flurbiprofen / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D011188:Potassium / Q000652:urine; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology*; D011458:Prostaglandins E / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D014545:Urinary Calculi / Q000188:drug therapy / Q000652:urine*
D011453:Prostaglandins; D011458:Prostaglandins E; D005480:Flurbiprofen; D012964:Sodium; D015232:Dinoprostone; D011188:Potassium; D002118:Calcium; D007213:Indomethacin