Abstract-Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effects of 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor (statin) therapy on proteinuria in normolipidemic patients with well-controlled hypertension have not been studied. A total of 63 normolipidemic (total cholesterol Ͻ240 mg/dL) and proteinuric (300 to 3000 mg/d) patients with well-controlled blood pressure (Ͻ140/90 mm Hg) were randomized to receive either placebo (nϭ32) or pravastatin (10 mg/d; nϭ31) after a 3-month placebo period. Pravastatin lowered proteinuria after 6 months by 54% (PϽ0.0001). Creatinine clearance was stable throughout the study in the 2 groups. Despite unchanged plasma endothelin-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with improvement in urinary protein excretion in pravastatin-treated patients (rϭ0.64, Pϭ0.001). The urinary excretion of retinol-binding protein decreased after pravastatin administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of IgG did not change significantly throughout the study in either group. Multivariate analysis revealed that proteinuria was only significantly correlated with statin use (PϽ0.0001, R 2 ϭ0.66). Linear regression analysis in the statin-treated group did not show any correlation between changes in lipid profiles and proteinuria regression. Thus, in addition to their primary function of antilipidemia, the addition of pravastatin to treatment for well-controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and lipid-lowering effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP-C in Europe in 2009. There are still relatively few published data on the long-term efficacy and safety of miglustat in patients with NP-C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1-3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration-penetration index scores among four evaluable patients (p > 0.05). Scores on the mini-mental state examination indicated an improvement in cognitive function during the first 3-6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression.