Statins increase AQP2 urinary excretion in hypercholesterolemic patients: a pleiotropic effect of statins of potential interest for patients with defects of AQP2 trafficking.

We reported that statins treatment increases AQP2 membrane expression in both cultured renal cells and in the renal tubule of mouse, but the ultimate effect in human kidney is unknown. Here, we conducted a pilot clinical study on AQP2 membrane expression in hypercholesterolemic patients requiring statin therapy. In humans, urinary AQP2 (uAQP2) is a non-invasive, reliable biomarker correlating with the amount of plasma membrane-expressed AQP2. Nineteen naïve patients with sustained hypercholesterolemia were enrolled along with 15 patients already under statin treatment for at least 1 year. We quantified the 24 h uAQP by ELISA. First, uAQP2 levels were compared in the two groups of patients. Then, time-dependent changes of uAQP2 levels were studied at baseline, week1 and week 2 in naïve patients starting statin treatment (simvastatin 10-20 mg/day). uAQP2 was significantly higher in patients chronically treated with statins compared to naïve (3839±319 pmol/24 h vs. 2819±234 pmol/24 h). Following statins treatment in naïve patients, uAQP2 shifted from 2471±358 pmol/24 h at baseline to 4443±493 pmol/24 h, at the end of the week1, and to 4003±450 pmol/24 h at the end of week2 of treatment. We conclude that the pleiotropic effect of statins on AQP2 plasma membrane abundance is attainable in humans at pharmacological doses. This finding has considerable relevance for those pathological conditions in which AQP2 membrane trafficking is impaired as in nephrogenic diabetes insipidus.