Clinical syndromes associated with disorders of renal tubular chloride transport: excess and deficiency of a circulating factor?

Two contrasting patients are described, one with pseudo-Bartter's syndrome induced by frusemide abuse and the other a case of hyporeninaemic hypoaldosteronism. The clinical and biochemical features of these two conditions are the opposite of each other and, in the first patient, the effects of frusemide were antagonised by treatment with indomethacin while in the second frusemide itself corrected the syndrome. The decreased pressor sensitivity to infused angiotensin II seen in the patient with pseudo-Bartter's syndrome was corrected with indomethacin and the enhanced pressor sensitivity seen in hyporeninaemic hypoaldosteronism was reversed with frusemide. Frusemide, an agent which blocks chloride transport at the ascending limb of Henle's loop, was respectively thus the cause and the cure of these conditions. On the basis of this the suggestion is made that Bartter's syndrome and hyporeninaemic hypoaldosteronism represent respectively an excess and a deficiency of a circulating factor similar to frusemide capable of blocking renal tubular chloride transport.