Causes of Reversible Nephrogenic Diabetes Insipidus: A Systematic Review

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Title: Causes of Reversible Nephrogenic Diabetes Insipidus: A Systematic Review
Authors: Garofeanu, M.D., Camelia G.; Weir, M.D., Mathew; Rosas-Arellano, M.D., Ph.D., Patricia; Henson, M.D., Garth; Garg, M.D., Amit X.; Clark, M.D., William F.
Publisher: American Journal of Kidney Diseases
Date Published: April 01, 2005
Reference Number: 686
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BACKGROUND: In nephrogenic diabetes insipidus (NDI), the kidney is unable to produce concentrated urine because of the insensitivity of the distal nephron to antidiuretic hormone (arginine vasopressin). In settings in which fluid intake cannot be maintained, this may result in severe dehydration and electrolyte imbalances. The risk for conversion of reversible to irreversible NDI seems to be a potential complication. This review summarizes the reversible causes of acquired NDI to facilitate earlier recognition and more effective treatment by clinicians. METHODS: Two reviewers independently searched MEDLINE, Experta Medica (EMBASE), and ISI bibliographic databases. Human studies that described NDI caused by drugs, substances, or metabolic disturbances were included. To evaluate the causal role of the risk factor, data were abstracted according to Koch's postulates. RESULTS: One hundred fifty-five studies published between 1957 and March 2004 described 30 risk factors. Of 155 studies, 58 studies provided a "definite" diagnosis of NDI; 83 studies, a "probable" diagnosis; and 14 studies, a "possible" diagnosis. Nine factors were considered "definite" causes of NDI; 15 factors, "probable" causes; and 6 factors, "possible" causes. The most reported risk factors were lithium (84 studies), antibiotics (16 studies), antifungals (11 studies), antineoplastic agents (9 studies), antivirals (8 studies), and metabolic disturbances (8 studies). Duration of NDI reversal, as well as conversion to irreversible symptoms, seemed to depend on the duration of exposure. CONCLUSION: Most risk factors for reversible NDI were medications, and their identification and removal resulted in resolution of the condition. Long-term treatment with lithium seemed to result in irreversible NDI.

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)

NDI can either be inherited or acquired. The acquired form of NDI may occur at any point in life. The causes of acquired NDI can be certain pharmaceutical drugs and certain metabolic disturbances such as low levels of potassium or calcium in the blood. Many times, acquired NDI will go away once the associated drug is no longer administered or the underlying metabolic disturbance is corrected.

Garofeanu, et al., reviewed 151 published studies that described NDI caused by pharmaceuticals or metabolic disturbances. Their goal was to summarize the causes of acquired NDI, the cessation or correction of which could cause the disappearance of NDI. The researchers reasoned that this information would help treating clinicians to be able to recognize and more effectively correct acquired NDI.

Their review of the studies revealed that the things most likely to be a risk for causing acquired NDI were: lithium (the most common causal factor reported), the antibiotics demeclocycline, ofloxacin, rifampin and netilmicin; the antifungal agents amphotericin B and possibly liposomal amphotericin B; the antineoplastic agents cyclophosphamide, ifosfamide, methotrexate and streptozocin; and the antiviral agents cidofovir, foscarnet, indinavir and tenofovir. The metabolic disturbances of low blood levels of calcium and phosphorus were also implicated as causal, as were other agents such as colchicine, lobenzarit, mesalaline, contrast agents, methoxyflurane, orlistat, pimozide, ethanol, and increased fluid intake.

Most of the studies reported that the acquired NDI ceased upon the cessation of exposure to the offending agent. The time it took for the NDI to reverse itself appeared to be dependent on the length of time the patient was exposed to the agent. One exception appeared to be lithium in which, in many cases, the NDI it created could not be reversed.