Vasopressin-Resistant Hyposthenuria in Advanced Chronic Renal Disease

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Abstract
Eleven of 13 patients with far advanced chronic renal disease of diverse etiologies were found to have urine that remained hypotonic to plasma in spite of the administration of a supramaximal dose of vasopressin. The vasopressin-resistant hyposthenuria seemed to be related more to the advanced nature of the disease than to the particular type of renal involvement. This defect has not previously been recognized as a common feature of end-stage renal disease, since before the present investigation, only a few patients with severe renal impairment had been studied. Possible pathophysiologic mechanisms resulting in this abnormality include anatomic derangement of the renal tubule or peritubular vasculature, an inhibitor of antidiuretic hormone, disordered calcium metabolism and osmotic diuresis per nephron. Although the urinary osmolality was always hypotonic it was not "fixed," every patient tested responding to a water load with further dilution.