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

Peritonitis and Exit Site Infections in First Nations Patients on Peritoneal Dialysis

Background and objectives: First Nations (FN) patients on peritoneal dialysis experience poor outcomes. Whether discrepancies exist regarding the microbiology, rate of infections, and outcomes between FN and non-FN peoples remains unknown