Lithium-Induced Nephrogenic Diabetes Insipidus Treated with Intravenous Ketorolac
| Title: | Lithium-Induced Nephrogenic Diabetes Insipidus Treated with Intravenous Ketorolac |
|---|---|
| Authors: | Burke, Cassandra; Fulda, MD, Gerard J.; Castellano, Jerry |
| Publisher: | Critical Care Medicine |
| Date Published: | November 01, 1995 |
| Reference Number: | 51 |
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Because the patient developed an intestinal obstruction, his lithium was temporarily suspended. Despite this, he began to experience polyuria and polydipsia. His blood sodium level was high, another indicator for NDI. The authors treated the patient with indomethacin in an effort to reduce his polyuria, but this proved inadequate. They tried giving the patient 30 milligrams of ketorolac every six hours. Four hours after the first treatment, the patient's urine became more concentrated and his urine output reduced dramatically. After three days, the ketorolac was discontinued due to concerns about the patient's breathing. His urine output began to increase, though he had no further episodes of NDI during his hospital stay.
Researchers are getting a better idea how lithium disrupts the kidney's urine concentrating process. Normally, when AVP binds with V2R, it activates a Gs protein which, in turn, stimulates adenyl cyclase, which catalyzes the conversion of adenosine triphosphate to the important metabolic regulator, cAMP. cAMP, through a series of steps not yet fully understood, is instrumental to a process which shuttles the water transporting protein, aquaporin-2 into the cell membranes of the principal cells of the kidney collecting duct. This makes them much more water permeable than usual, allowing the kidney to reabsorb water and concentrate urine.
Researchers postulate that lithium may block the activation of adenyl cyclase, which reduces the concentration of cAMP. In addition, lithium may further decrease cAMP levels by increasing its destruction by phosphodiesterese (a normal process intensified by lithium). Also, lithium may increase the ability of VP to produce prostaglandin E2, a substance which promotes excessive urination.
Indomethacin is thought to be able to increase cellular levels of cAMP and increase sodium reabsorption. After it failed to reduce the patient's polyuria, the authors tried ketorolac, which is supposed to act similarly. In this case, the ketorolac worked, leading the authors to conclude not that it is more effective than indomethacin, but that it too may be an effective alternative if other drugs are not working to reduce polyuria brought on by NDI.