Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study. We measured left ventricular mass index (LVMI) with cardiac magnetic resonance imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of the brachial artery, and evaluated central arterial stiffness by pulse-wave analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial function (P=0.009), and improved the central augmentation index (P=0.015). This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD. Because LVH and endothelial dysfunction associate with prognosis, these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH.

Oxidative stress has been increasingly linked to the high incidence of cardiovascular events in patients with chronic kidney disease (CKD), especially as traditional cardiovascular risk factors seem to not be able to account for the huge cardiovascular morbidity and mortality in this population group. Oxidative stress is increased in patients with renal impairment as a result of increased oxidant activity and reduced antioxidant capacity, and this is increased in a graded manner with increasing renal dysfunction. Inflammation, which is also present in CKD, further amplifies the oxidant generation process. The two clinical sequelae of oxidative stress are endothelial dysfunction and left ventricular hypertrophy, which have adverse cardiovascular consequences. With our new understanding of oxidative stress, it is now important to assess treatment options that reduce it in the hope that they reverse endothelial dysfunction and left ventricular hypertrophy and the clinical sequelae of these abnormalities.

Skilled object lifting requires the prediction of object weight. When lifting new objects, such prediction is based on well-learned size-weight and material-density correlations, or priors. However, if the prediction is erroneous, people quickly learn the weight of the particular object and can use this knowledge, referred to as sensorimotor memory, when lifting the object again. In the present study, we explored how sensorimotor memory, gained when lifting a given object, interacts with well-learned material-density priors when predicting the weight of a larger but otherwise similar-looking object. Different groups of participants 1st lifted 1 of 4 small objects 10 times. These included a pair of wood-filled objects and a pair of brass-filled objects where 1 of each pair was covered in a wood veneer and the other was covered in a brass veneer. All groups then lifted a larger, brass-filled object with the same covering as the small object they had lifted. For each lift, we determined the initial peak rate of change of vertical load-force rate and the load-phase duration, which provide estimates of predicted object weight. Analysis of the 10th lift of the small cube revealed no effects of surface material, indicating participants learned the appropriate forces required to lift the small cube regardless of object appearance. However, both surface material and core material of the small cube affected the 1st lift of the large block. We conclude that sensorimotor memory related to object density can contribute to weight prediction when lifting novel objects but also that long-term priors related to material properties can influence the prediction.