Association between sclerostin levels and vascular outcomes in kidney transplantation patients.

BACKGROUND: The impact of circulating sclerostin levels on vascular calcification has shown conflicting results depending on the target population and vascular anatomy. This study investigated the associations of sclerostin levels with vascular outcomes in kidney transplant patients. METHODS: In a prospective observational study of the Korean Cohort Study for Outcome in Patients with Kidney Transplantation, 591 patients with serum sclerostin level data prior to transplantation were analyzed. The main predictor was the pre-transplant sclerostin level. Vascular outcomes were the abdominal aortic calcification score and brachial-ankle pulse wave velocity measured at pre-transplant screening and three and five years after kidney transplantation. RESULTS: In linear regression analysis, sclerostin level positively correlated with changes in abdominal aortic calcification score between baseline and five years after kidney transplantation (coefficient of 0.73 [95% CI, 0.11-1.35] and 0.74 [95% CI, 0.06-1.42] for second and third tertiles, respectively, vs the first tertile). In a longitudinal analysis over five years, using generalized estimating equations, the coefficient of the interaction (sclerostin × time) was significant with a positive value, indicating that higher sclerostin levels were associated with faster increase in post-transplant abdominal aortic calcification score. Linear regression analysis revealed a positive association between pre-transplant sclerostin levels and changes in brachial-ankle pulse wave velocity (coefficient of 126.7 [95% CI, 35.6-217.8], third vs first tertile). Moreover, a significant interaction was identified between sclerostin levels and brachial-ankle pulse wave velocity at five years. CONCLUSIONS: Elevated pre-transplant sclerostin levels are associated with the progression of post-transplant aortic calcifications and arterial stiffness.

The association between the vascular endothelial growth factor-to-cancer antigen 125 ratio in peritoneal dialysis effluent and the epithelial-to-mesenchymal transition in continuous ambulatory peritoneal dialysis.

We examined peritoneal growth factors, mesothelial mass, and epithelial-to-mesenchymal transition (EMT) in response to peritoneal exposure to peritoneal dialysate with standard and low concentrations of glucose degradation products (GDPs). We randomized 56 incident continuous ambulatory peritoneal dialysis (CAPD) patients to receive either low-GDP (30 patients) or high-GDP (standard) peritoneal dialysis (PD) solution (26 patients). The effects of the PD solutions on EMT and peritoneal growth factors in overnight dialysate effluent were compared at 1, 6, and 12 months. Assessment of EMT was performed after human peritoneal mesothelial cells (HPMCs) were cultured from overnight effluent. The low-GDP solution group showed significantly higher dialysate levels of cancer antigen 125 (CA125), fibronectin, transforming growth factor beta(TGFbeta)-induced gene product (betaig-h3), and interleukin-6 (IL-6), but the rate of EMT was significantly lower in the low-GDP solution group during the initial 12 months of CAPD treatment. After adjusting peritoneal growth factors for dialysate CA125 concentration, the low-GDP solution group showed significantly lower ratios of fibronectin/CA125, betaig-h3/CA125, IL-6/CA125, TGFbeta/CA125, and vascular endothelial growth factor (VEGF)/CA125 than did patients in the high-GDP (standard) solution group. Factors associated with higher EMT were the type of solution (high in GDPs), the mass of HPMCs (low CA125), and higher VEGF/CA125. Adjustment of dialysate VEGF for effluent CA125 revealed a significant association with EMT. It suggests that fibroblastoid transition from HPMCs could be affected by the intraperitoneal VEGF per unit mass of HPMCs.