Nephrogenic Diabetes Insipidus (NDI)



NDI is a specific defect in the response of the collecting tubule to ADH. ADH release in re­sponse to osmotic or volume stimulation and cir­culating levels of ADH are normal, yet the urine is persistently hypotonic to plasma. Aside from this specific concentrating defect, renal function is normal. NDI may occur either as a rare, X-linked hereditary disorder or as an acquired defect sec­ondary to lithium or demeclocycline therapy.

Hereditary NDI presents in infancy as repeated bouts of fever and altered mental status. These symptoms are the result of hypertonic volume de­pletion and encephalopathy. In later life, inces­sant thirst and persistent polyuria dominate the clinical picture. Urinary tract dilation may result from the massive volumes of urine excreted daily, 15 to 20 L in adults. Neurological deficits may be seen as a result of repeated bouts of hypertonic encephalopathy.

The diagnosis is made by family history, a fail­ure to concentrate the urine after 12 to 18 hours of dehydration, and a failure to raise urine os­molality above that of plasma in response to ex­ogenous ADH. Treatment consists of assurance of ready access to and intake of water, plus a thiazide diuretic. Thiazide diuretics plus salt restriction cause a modest reduction in ECF volume, which causes a greater volume of the glomerular filtrate to be absorbed as isotonic fluid in the proximal nephron. Therefore, a lesser volume of hypotonic fluid is generated in the loop of Henle, delivered to the ADH-unresponsive collecting duct, and ex­creted in the final urine.

Acquired NDI is generally incomplete and is ex­pressed as a dramatic reduction in maximal uri­nary concentration. The defect almost always dis­appears with cessation of the demeclocycline or lithium.