Bisphosphonate FYB-931 Prevents High Phosphate-Induced Vascular Calcification in Rat Aortic Rings by Altering the Dynamics of the Transformation of Calciprotein Particles.

Patients with chronic kidney disease develop vascular calcification, owing to impaired calcium and phosphate metabolism. The prevention of vascular calcification is important to improve the prognosis of such patients. In this study, we investigated whether treatment with FYB-931, a novel bisphosphonate compound, prevents vascular calcification in rat aortic rings cultured in high-phosphate medium for 9 days, assessed by measurement of the calcium content and the degree of calcium deposition, visualized using von Kossa staining. The effect on the transformation of calciprotein particles (CPPs) from primary to secondary CPPs was assessed using a fluorescent probe-based flow cytometric assay. FYB-931 dose-dependently prevented high phosphate-induced aortic calcification, but failed to rapidly cause the regression of high phosphate-induced vascular calcification once it had developed. Furthermore, the treatment dose-dependently inhibited the high phosphate-induced transformation from primary to secondary CPPs. In addition, the treatment with FYB-931 prevented the transformation from primary to secondary CPPs in vitamin D3-treated rats as a model of ectopic calcification, consistent with the results from rat aortic rings. In conclusion, treatment with FYB-931 prevents high phosphate-induced rat aortic vascular calcification by altering the dynamics of CPP transformation. This finding suggests that inhibition of the transformation from primary to secondary CPPs is an important target for the prevention of vascular calcification in patients with chronic kidney disease.

Association between serum lipids, polyunsaturated fatty acids, and prognosis in maintenance hemodialysis patients.

INTRODUCTION: Risks of mortality and cardiovascular disease (CVD) are significantly higher in hemodialysis (HD) patients than in the general population, where dyslipidemia is an established risk factor for CVD and mortality. There is no clear conclusion, however, whether dyslipidemia is a significant risk factor for CVD and mortality in HD patients. Similarly, the association between the polyunsaturated fatty acids (PUFAs) and the mortality is not clear in HD patients. METHODS: We retrospectively investigated mortality and CVD events in 420 HD patients. We classified patients into high- and low-lipid groups depending on their lipid levels. Survival rates were calculated using the Kaplan-Meier analysis and evaluated by the log-rank test. The risk estimates were computed using a multivariate Cox proportional hazard analysis. FINDINGS: During their follow-up (June 2011 to June 2016), 151 patients died (37 of CVD), and 112 patients experienced new CVD events. On Kaplan-Meier analysis, the number of all-cause deaths and CVD events were significantly higher in the low HDL-cholesterol group (P < 0.01, log-rank test). Similarly, the number of all-cause deaths was significantly higher in the high eicosapentaenoic acid/arachidonic acid ratio group (P < 0.01, log-rank test). Multivariate Cox proportional analysis showed that HDL-cholesterol was a significant prognostic indicator for new onset of CVD events (low: 0, high: 1, hazard ratio 0.66, 95% confidence interval 0.44-0.97; P = 0.04). DISCUSSION: In HD patients, LDL-cholesterol and non-HDL-cholesterol levels are not associated with mortality or CVD events. The HDL-cholesterol level, however, is an independent predictor of new CVD events even in HD patients.

Correlation between haemoglobin level and type of erythropoiesis-stimulating agent at initiation of haemodialysis.

Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients with chronic kidney disease is correlated with cardiovascular disease and mortality. Objective This study was performed to determine whether short- and long-acting erythropoiesis-stimulating agents are correlated with the pre-haemodialysis haemoglobin level in patients with chronic kidney disease. Setting This study was conducted at the Blood Purification Center in Wakayama Medical University. Method We enrolled 364 patients undergoing initiation of haemodialysis from January 2009 to June 2015 and analysed them for > 3 months prior to the initiation of haemodialysis. In total, 168 patients were included in the final analysis based on the inclusion and exclusion criteria. Main outcome measures The correlation of the haemoglobin level at the initiation of haemodialysis with various factors according to the type of erythropoiesis-stimulating agent used. Results The median haemoglobin level was 8.8 g/dL, and long-acting erythropoiesis-stimulating agents were used by 69.6% of the patients. Long-acting erythropoiesis-stimulating agents were used significantly more often in patients with high than low haemoglobin levels. The haemoglobin levels at the initiation of haemodialysis and 1 month prior tended to be significantly higher in patients taking long-than short-acting erythropoiesis-stimulating agents. The serum levels of iron and albumin and the use of long-acting erythropoiesis-stimulating agents were independently correlated with the haemoglobin level at the initiation of haemodialysis in the multivariate regression analysis. In addition, the left ventricular mass index was significantly correlated with the haemoglobin level at the initiation of haemodialysis. Conclusion Long-acting erythropoiesis-stimulating agents were correlated with higher haemoglobin levels and may be more useful for patients with a low left ventricular mass index at the initiation of haemodialysis.

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression.

BACKGROUND: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). METHODS: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. RESULTS: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. CONCLUSION: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.

Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies.

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short- and long-term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end-stage renal disease requiring dialysis or transplantation is attracting increased attention.