Summary— In a clinical study of 275 idiopathic stone formers the GFR was significantly raised in hypercalciuric patients compared with normal controls P<0.001). The possibility that the mechanism underlying hypercalciuria and raised GFR may be prostaglandin-mediated was considered because it is now well established that prostaglandins regulate intra-renal haemodynamics and influence tubular electrolyte excretion.
Experiments were performed in conscious Sprague Dawley rats to determine the changes in calcium and sodium excretion following prostaglandin synthetase inhibition with indomethacin. Both calcium and sodium excretion together with urine flow were significantly reduced (P<0.002). Further experiments were performed in anaesthetised monkeys (Macacca 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 GFR or blood pressure.
Selected hypercalciuric patients were treated with indomethacin, which resulted in a significant fall in urinary calcium excretion (P<0.001). This clinical and experimental study suggests that PGE2is the hormone which determines the renal handling of calcium by controlling renal tubular function.