A Double-Blind, Randomized, Placebo-Controlled Pilot Trial of Atorvastatin for Nephrogenic Diabetes Insipidus in Lithium-Users.

OBJECTIVE Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease amongst lithium users. There is limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. METHOD We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20mg/day atorvastatin vs. placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. RESULTS Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/Kg [95% CI, -35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were -0.13 L [95% CI, -0.54, 0.28] and 98.68 [95% CI, -190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100mOsm/Kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs. 22.58% (7/31); Cohen's d = 0.66). CONCLUSION Among lithium users with NDI, atorvastatin 20mg/day did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.