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.

Breath tests with novel 13C-substrates for clinical studies of liver mitochondrial function in health and disease.

Mitochondrial dysfunction determines the onset and progression of chronic deleterious conditions including liver diseases. The in vivo assessment of mitochondrial function, by providing more insight into the pathogenesis of liver diseases, would be a helpful tool to study specific functions and to develop diagnostic, prognostic and therapeutic strategies. The application of breath tests in the clinical setting to evaluate mitochondrial fitness may elegantly and noninvasively overcome the difficulties due to previous complex techniques and may provide clinically relevant information, i.e the effects of drugs presenting mitochondrial liabilities. Substrates meeting this requirement include alpha-ketoisocaproic acid and methionine, both decarboxylated by mitochondria. Long and medium chain fatty acids that are metabolized through the Krebs cycle and benzoic acid, which undergoes glycine conjugation, may also reflect the mitochondrial performance. This review focuses on the utility of breath tests to assess mitochondrial function in humans, thus contributing to unravel potential mechanisms associated with the dysfunction of this organelle network in the pathophysiology of liver diseases.

Dynamic 4D MR angiography versus multislice CT angiography in the evaluation of vascular hepatic involvement in hereditary haemorrhagic telangiectasia.

PURPOSE: Hereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is a rare autosomal dominant disorder characterised by mucocutaneous or visceral vascular abnormalities that may be widely distributed throughout the cardiovascular system. The purpose of this study was to compare multislice computed tomography angiography (MSCTA) and 4D dynamic contrast-enhanced magnetic resonance angiography (D-MRA) for evaluating vascular hepatic involvement in patients with HHT. MATERIALS AND METHODS: Fifty-two consecutive HHT patients underwent MSCTA and D-MRA examinations for systematic analysis of vascular visceral involvement. The images from the two techniques were reviewed independently by two expert radiologists to identify the following vascular abnormalities: telangiectases or large vascular masses; perfusion disorders [transient hepatic attenuation differences (THADs)]; hepatic arteriovenous malformations (HAVMs). Data, as well as diameters of the common hepatic artery and portal vein, were compared with Cohen's kappa statistic, Student's t test and receiver operating characteristic (ROC) curve analysis, as appropriate. RESULTS: Both MSCTA and D-MRA detected one or more of the following hepatic vascular abnormalities in 36/52 cases (telangiectases in 29/52, THADs in 23/52 and HAVMs in 25/52[CE1]). A good concordance was found between the two techniques when determining the type of hepatic shunt (κ=0.9). No statistically significant differences were found when comparing mean common hepatic artery and portal vein diameters (p=0.09 and 0.22, respectively) and their accuracy in predicting HAVMs. CONCLUSIONS: D-MRA has the same diagnostic accuracy as MSCTA and has the advantage of being less invasive due to the absence of ionising radiation.