Physiologic Studies in Nephrogenic Diabetes Insipidus1

Abstract

In the patient with nephrogenic diabetes insipidus, it is possible to study the effect of various factors altering the renal concentrating and diluting mechanism with the assurance that ADH is not contributing to the results. Several of these factors have been studied. In the patient with “complete” NDI, dehydration without a fall in GFR does not increase urine concentration more than Pitressin does. Some patients with incomplete disease, however, may produce a hypertonic urine with dehydration, despite total unresponsiveness to exogenous vasopressin. Prolonged cortisol administration appears to augment all parameters of a maximal water diuresis. During a sustained water diuresis, the infusion of isoncotic albumin in saline elicits variable changes in diuresis that are correlated better with changes in solute excretion than with renal hemodynamics. An acute and severe reduction of the GFR does not cause the production of a hypertonic urine. The pattern of daily urine excretion is abnormal, with nearly equal day and night volumes. During chlorothiazide therapy, nocturnal urine excretion may greatly exceed the diurnal volume. The antidiuresis noted with chlorothiazide therapy is not related to its direct effect on the distal tubule in decreasing CH₂O, but is probably secondary to its ability to produce a reduction of total body sodium with the concomitant effect of depressing renal hemodynamics and increasing the reabsorption of sodium and water in the nephron proximal to the distal convoluted tubule.