Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD)

Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD).BackgroundThe majority of patients with chronic kidney disease (CKD) have excessive vascular calcification; however, most studies demonstrate that a subset of CKD patients do not have, nor develop, vascular calcification despite similar exposure to the uremic environment. This suggests protective mechanisms, or naturally occurring inhibitors, of calcification may be important.MethodsIn order to determine the role of three inhibitors, fetuin-A, matrix gla protein (MGP), and osteoprotegerin (OPG) in the vascular calcification observed in patients with CKD-5, we (1) measured serum levels of these inhibitors and compared the levels to calcification assessed by computed tomography (CT); (2) examined arteries from CKD-5 patients by immunostaining for these inhibitors; and (3) examined the expression and effect of these inhibitors in cultured bovine vascular smooth muscle cells (BVSMCs) incubated in serum pooled from uremic patients compared to healthy controls.ResultsThere was a negative correlation of coronary artery calcification scores with serum fetuin-A levels (r=-0.30, P = 0.034) and a positive association with OPG levels (r = 0.29, P = 0.045). There was increasing immunostaining for both fetuin-A and MGP in arteries with increasing calcification graded semiquantitatively (P < 0.003). In vitro, fetuin-A added to mineralizing BVSMCs inhibited mineralization (P < 0.001). Compared to normal serum, BVSMCs incubated with uremic serum had a progressive increase in MGP expression with mineralization (P < 0.001) and increased expression of OPG in BVSMCs (P < 0.04).ConclusionThese data demonstrate that fetuin-A, OPG, and MGP play an important role in the pathogenesis of uremic vascular calcification

Optic neuritis

Acute optic neuritis is the most common optic neuropathy affecting young adults. Exciting developments have occurred over the past decade in understanding of optic neuritis pathophysiology, and these developments have been translated into treatment trials. In its typical form, optic neuritis presents as an inflammatory demyelinating disorder of the optic nerve, which can be associated with multiple sclerosis. Atypical forms of optic neuritis can occur, either in association with other inflammatory disorders or in isolation. Differential diagnosis includes various optic nerve and retinal disorders. Diagnostic investigations include MRI, visual evoked potentials, and CSF examination. Optical coherence tomography can show retinal axonal loss, which correlates with measures of persistent visual dysfunction. Treatment of typical forms with high-dose corticosteroids shortens the period of acute visual dysfunction but does not affect the final visual outcome. Atypical forms can necessitate prolonged immunosuppressive regimens. Optical coherence tomography and visual evoked potential measures are suitable for detection of neuroaxonal loss and myelin repair after optic neuritis. Clinical trials are underway to identify potential neuroprotective or remyelinating treatments for acutely symptomatic inflammatory demyelinating CNS lesions