How is NDI treated?

Topic: Health Care
Author: Bichet, Daniel G.
There is as yet no cure for inherited NDI, though researchers are hopeful that their study of the genetic basis of the disorder will lead to some form of genetic therapy that will cure it. Currently, NDI is managed by:

  1. ensuring ready access to water,

  2. following a low-sodium (and sometimes low-protein) diet, and

  3. using thiazide diuretics, alone or in combination with a prostaglandin inhibitor or a potassium-sparing diuretic, to reduce the volume of urine output.

Thiazide diuretics can reduce an NDI patient's polyuria, but they may also deplete the body's stores of potassium. This depletion can cause other symptoms and may be dangerous. When taking thiazide diuretics, the patient's potassium levels must be monitored. To maintain sufficient potassium in the body, the addition of potassium supplements or amiloride (but not both) to the treatment regime may be required.

Walter Rosenthal and Alexander Oksche of the Forschungsinstitut für Molekulare Pharmakologie in Berlin, Germany state in The Molecular Basis of Nephrogenic Diabetes Insipidus that combining a thiazide (such as hydrochlorothiazide) with a potassium-sparing diuretic (such as amiloride) may be more effective than using a thiazide alone. Sometimes thiazides are used in combination with the prostaglandin inhibitor, indomethacin. Elevated levels of Prostaglandin E2 (PGE2) have been reported in NDI patients, and PGE2 in the kidney interferes with the activity of AVP. Indomethacin inhibits the synthesis of prostaglandin in the kidney, thus reducing polyuria in cases of both inherited and acquired NDI. However, Bichet recommends using a prostaglandin inhibitor only in an emergency situation and then only for a short time. Rosenthal and Oksche mention that the combination of thiazides and amiloride may be preferable because they have less potential side effects than a combination of indomethacin and thiazide. Indomethacin, a nonsteroidal anti-inflammatory agent, often causes headaches and dizziness, or an increased risk of gastrointestinal disorders. Also, if administered in the first year of life, indomethacin increases the risk of kidney disease.

Thiazide diuretics should be used with care in cases of lithium-induced NDI as they reduce the degree to which the kidney can excrete lithium, thereby setting the stage for a toxic build-up of lithium. Amiloride is more widely used in these cases as it inhibits the accumulation of lithium while blunting lithium's inhibiting action of water reabsorption. In The Management of Diabetes Insipidus in Adults, Dr. Irwin Singer of the Veterans Affairs Medical Center in Miami, Florida, USA, et al., notes that while thiazides rob the body of potassium, amiloride inhibits excretion of potassium in the urine. Dr. Patricia Adams from Smiley's Clinic in Minneapolis, Minnesota, USA states in Evaluation and Management of Diabetes Insipidus that thiazide diuretics and amiloride deplete total body salt, which allows the kidneys to more readily absorb water. However, this improved water absorption is negated by a diet heavy in salt, so low-sodium diets such as that recommended in Diet and Nutrition by Cristine Trahms and Beth Ogata of the University of Washington in Seattle, Washington, USA are prescribed for NDI patients.

A couple of other pharmacalogical management tools have shown some, though variable, results. Burke, et al., in a case report in Critical Care Medicine found that a patient with lithium-induced NDI showed a dramatic increase in urine osmolality along with a significant decrease in urine output after the patient was treated with ketorolac, a non-steroidal anti-inflammatory agent. However, the long-term effects of this drug as used for this purpose are unknown. Weinstock and Moses in Desmopressin and Indomethecin Therapy for NDI in Patients Receiving Lithium Carbonate, report that some patients can have a partial reduction in urine output in response to large doses of dDAVP. However, other patients in the same condition did not.