Simvastatin increases AQP2 urinary excretion in hypercholesterolemic patients: A pleiotropic effect of interest for patients with impaired AQP2 trafficking.

We previously reported that statins improve the symptoms of X-linked nephrogenic diabetes insipidus (X-NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of statins on AQP2 trafficking and kidney-concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24-hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine-concentrating defects caused by defective AQP2 plasma membrane trafficking, like X-NDI.