Systematic reviews and meta-analyses
Causes of reversible nephrogenic diabetes insipidus: A systematic review

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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.

Section snippets

Research questions

The primary questions of this review are: (1) Which putative factors have been associated with reversible NDI? (2) How accurate was the diagnosis of reversible NDI? (3) Was the association between the factor and reversible NDI causal?

Finding relevant studies

Two reviewers independently searched for relevant articles in MEDLINE (OVID, 1966 to May 2004), Experta Medica (EMBASE, 1980 to May 2004), and ISI (1990 to May 2004) bibliographic databases. Any article considered potentially relevant by any reviewer was retrieved

Study selection

More than 2,000 abstracts were screened, and 354 potentially relevant full-text articles were retrieved. Forty-nine studies published in other languages were included (ie, Italian, German, Spanish, Japanese, Hungarian, Dutch, Finnish, French, and Romanian). One hundred fifty-five reports met inclusion criteria and were included in the final analysis. They included 110 case reports, 29 cohort studies, and 16 cross-sectional studies. The most frequently reported risk factor was lithium (84

Discussion

Acquired NDI represents a urinary concentration defect of renal origin believed to be reversible with correction or removal of the causative agent. Its severity tends to be judged in conjunction with the severity of the underlying disease and the extension of the renal damage. A recent attempt to better define it has made the distinction between a “narrow definition” of NDI, for which only the permeability of the collecting duct is affected by drugs or metabolic disturbances, and a “broad

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