Nephrogenic Diabetes Insipidus in a Lethargic Lithium-Treated Patient
| Title: | Nephrogenic Diabetes Insipidus in a Lethargic Lithium-Treated Patient |
|---|---|
| Authors: | Meinardi, M.D., Johan R.; Donders, S.H.J. |
| Publisher: | Netherlands Journal of Medicine |
| Date Published: | March 01, 1997 |
| Reference Number: | 5 |
We report on a patient who developed severe lithium-induced nephrogenic diabetes insipidus (NDI) and neurotoxicity, despite recommended serum lithium levels. Hydrochlorothiazide and indomethacin appeared effective antipolyuric drugs, which led to a normalization of serum osmolality. After re-initiating lithium therapy, with lithium levels around 0.3 mmol/l, recurrence of NDI or neurotoxicity was not observed, despite discontinuation of indomethacin and hydrochlorothiazide. Together with hypothyroidism, NDI and neurotoxicity must be considered in lethargic lithium-treated patients.
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)
The authors lowered, then discontinued, the patient's lithium dosage and treated him with indomethacin and hydrochlorothiazide to reduce urine output and blood sodium levels. Later, lithium was readministered at lowered levels, even though the patient still had NDI. However, his NDI began to normalize. Four weeks after his discharge from the hospital, the patient was readmitted. All medications were stopped, then five days later lithium was reintroduced at even lower levels. NDI did not reoccur even though indomethacin and hydrochlorothiazide use was discontinued.
Lithium has become the most common cause of acquired NDI. Of patients receiving long-term lithium therapy, 30% - 70% develop a urinary concentrating defect, 2% - 35% develop polyuria, and 4.5% - 20% develop NDI.
Lithium interferes with the production of an important metabolic regulator called cAMP which is part of the molecular sequence that leads to the ability of the kidney to concentrate urine. This prevents the water transporting proteins called aquaporin-2 (AQP2) from inserting themselves in the apex of the cell membranes of the principal cells of the kidney collecting ducts. Normally, AQP2s allow these cell membranes to let much more water than usual flow through them, which is how the kidneys are able to reabsorb water and concentrate urine. If the AQP2s cannot reach the cell membranes, the kidneys are not able to perform these functions.
Several reports mention that indomethacin therapy helps reduce NDI-related polyuria since it seems to inhibit prostaglandin synthesis, which, in turn, would allow for more cAMP production. However, indomethacin can promote lithium toxicity. Hydrochlorothiazide helps decrease extracellular fluid volume and stimulate fluid reabsorption. This reduces the amount of fluid that part of the kidney has to deal with. It must be used carefully because it too, can lead to lithium toxicity.
The authors recommend administering lower lithium levels to the elderly and monitoring them for NDI and lithium toxicity.