EUH Resident Report: What is the current literature on indomethacin as treatment for lithium DI?

The Bottom Line: Twenty percent of patients treated with lithium develop nephrogenic diabetes insipidus (NDI), a disorder in which the kidney is unable to concentrate urine (Kortenoven et al, 2012). Indomethacin (and controlled volume reduction if continued high urine output), while observing renal function, appears the emergency treatment of choice for serious complications of nephrogenic diabetes insipidus (Lam & Kjellstrand, 1997).

Summary: Kortenoeven et al (2012) note that inhibition of COX by indomethacin, leading to reduced PGE2 and PGF levels, or dexamethasone-induced downregulation of COX-2 both increased AQP2 abundance, while PGE2 addition reduced AQP2 abundance. Lithium did not change the prostaglandin levels, and indomethacin and dexamethasone did not prevent lithium-induced AQP2 downregulation.

For further reading and reference, a 1989 case study in Archives of Internal Medicine found that “a single dose of indomethacin resulted in a dramatic decrease in urine volume and increase in urine osmolality that persisted for several hours, and was independent of renal hemodynamic changes. Subsequently, the patient experienced a sustained, favorable effect on her polyuria during long-term (3 months) indomethacin therapy without a deleterious effect on her renal function. Indomethacin may be a useful therapeutic tool for the amelioration of lithium-induced NDI” (p.1123).

References: Allen, HM, et al. “Indomethacin in the treatment of lithium-induced nephrogenic diabetes insipidus.” Archives of Internal Medicine 1989; 149(5):1123-1126.

Kortenoven et al. “Lithium reduces aquaporin-2 transcription independent of prostaglandins.” American Journal of Physiology Cell Physiology 2012; 302(1):C131-C140.

Lam, SS & Kjellstrand, C. “Emergency treatment of lithium-induced diabetes insipidus with nonsteroidal anti-inflammatory drugs.” Renal Failure 1997; 19(1): 183-188.

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