Vascular calcification is closely related to cardiovascular morbidity and mortality. Accumulating data indicate that oxidative stress is associated with dysfunction of various organs, including cardiovascular diseases in chronic kidney disease (CKD). However, it remains undetermined if oxidative stress induced by uremia promotes arterial medial calcification. The present study investigated the role of oxidative stress in the pathogenesis of arterial medial calcification in uremic rats. Rats with uremia induced by adenine-rich diet progressively developed arterial medial calcification, which was accompanied by time-dependent increases in both aortic and systemic oxidative stress. Immunohistochemical and biochemical analyses showed that the arterial medial calcification progressed in a timedependent manner that is parallel to the osteogenic transdifferentiation of vascular smooth muscle cells. Accumulation of oxidative stress was also identified in the calcified regions. Time-course studies indicated that both oxidative stress and hyperphosphatemia correlated with arterial medial calcification. Tempol, an antioxidant, ameliorated osteogenic transdifferentiation of vascular smooth muscle cells and arterial medial calcification in uremic rats, together with reduction in aortic and systemic oxidative stress levels, without affecting serum biochemical parameters. Our data suggest that oxidative stress induced by uremia can play a role in the pathogenesis of vascular calcification in CKD, and that antioxidants such as tempol are potentially useful in preventing the progression of vascular calcification in CKD. ß

The authors report the use of neuroendoscopic third ventriculostomy to treat successfully both hydrocephalus and syringomyelia associated with fourth ventricle outlet obstruction. A 27-year-old woman presented with dizziness, headache, and nausea. Magnetic resonance (MR) imaging demonstrated dilation of all ventricles, downward displacement of the third ventricular floor, obliteration of the retrocerebellar cerebrospinal fluid (CSF) space, funnellike enlargement of the entrance of the central canal in the fourth ventricle, and syringomyelia involving mainly the cervical spinal cord. Cine-MR imaging indicated patency of the aqueduct and an absent CSF flow signal in the area of the cistema magna, which indicated obstruction of the outlets of the fourth ventricle. Although results of radioisotope cisternography indicated failure of CSF absorption, neuroendoscopic third ventriculostomy completely resolved all symptoms as well as the ventricular and spinal cord abnormalities evident on MR images. Neuroendoscopic third ventriculostomy is an important option for treating hydrocephalus in patients with fourth ventricle outlet obstruction.

We elucidate the underlying mechanisms of bidirectional cardiorenal interaction, focusing on the sympathetic nerve driving disruption of the local renin-angiotensin system (RAS). A rat model of N(ω)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in the heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite the blood pressure being kept the same between the two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in the kidney and increased in the heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of the heart and circulating AGT excretion from glomeruli of the kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and the degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within the same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.

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The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland (PTG) volume has been scarcely investigated in patients with moderate to advanced secondary hyperparathyroidism (SHPT). The present study was a prospective observational study to determine the effect of cinacalcet treatment on PTG volume and serum biochemical parameters in 60 patients with renal SHPT, already treated with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical parameters and PTG volumes were performed periodically, which were analyzed by stratification into tertiles across the baseline parathyroid hormone (PTH) level or PTG volume. We also determined the factors that can estimate the changes in PTG volume and the achievement of the target PTH range by multivariable analyses. Two years of cinacalcet treatment significantly decreased the serum levels of PTH, calcium, and phosphate, followed by the improvement of achieving the target ranges for these parameters recommended by the Japanese Society for Dialysis Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and also decreased the serum PTH level independent of the baseline serum PTH level and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2 years. Multivariable analysis showed that patients with nodular PTG at baseline and patients with higher serum calcium and PTH levels at 1 year were likely to exceed the target range of PTH at two years. In conclusion, cinacalcet treatment with intravenous VDRA therapy decreased both PTG volume and serum intact PTH level, irrespective of the pretreatment PTG status and past treatment history.