Effect of vitamin D receptor activators on cardiovascular events in patients on hemodialysis-A post hoc analysis of the LANDMARK study.

INTRODUCTION: The clinical benefit of vitamin D receptor activators (VDRA) in patients with well-controlled secondary hyperparathyroidism undergoing dialysis remains unclear. METHODS: This post hoc analysis of the LANDMARK study investigates if VDRA use is associated with cardiovascular benefits. Data of 2135 patients undergoing hemodialysis who were at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity-score matching. RESULTS: The hazard ratio (HR) for VDRA use was 0.99 (95% confidence interval [CI]: 0.67-1.46; p = 0.945) for cardiovascular events and 0.89 (95% CI: 0.62-1.28; p = 0.541) for all-cause mortality at baseline. Among patients who always used VDRA, the HR was 1.12 (95% CI: 0.67-1.89; p = 0.666) for cardiovascular events and 1.11 (95% CI: 0.67-1.85; p = 0.688) for all-cause mortality compared to those who never used VDRA. CONCLUSION: The use of VDRA does not reduce the risks of cardiovascular events or all-cause mortality in patients on dialysis with well-controlled secondary hyperparathyroidism.

An update on phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a review of safety profiles.

INTRODUCTION: Hyperphosphatemia is an inevitable complication for patients undergoing dialysis, as is the resulting need for treatment with phosphate binders. Currently, various phosphate binders are clinically available. In addition to their phosphate-lowering activity, individual phosphate binders have differing safety profiles and off-target actions. AREAS COVERED: This paper reviews the safety of phosphate binders and issues to be resolved. EXPERT OPINION: Calcium-based phosphate binders are well tolerated but may increase calcium overload risk. Sevelamer reduces serum cholesterol levels and exerts anti-inflammatory effects. Compared to sevelamer, bixalomer is associated with fewer gastrointestinal symptoms. Aluminum-containing binders, lanthanum carbonate, and sucroferric oxyhydroxide exhibit strong phosphate-lowering activity. Although ferric citrate reduces erythropoiesis-stimulating agents and intravenous iron doses, its use requires monitoring of iron metabolic markers to avoid overload. Occasionally, combined use of multiple phosphate binders can offer the advantages of each phosphate binder while minimizing their drawbacks; thus, this may be desirable according to individual patients' conditions and comorbidities. However, increased pill burden and nonadherence to phosphate binders emerge as new problems. We expect that novel therapeutic strategies will be developed to resolve these issues.

Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms.

Bixalomer (Bix) is an amine-functional polymer, non-calcium-containing phosphate (P) binder, and has been clinically available in Japan recently. Bix is expected to cause fewer gastrointestinal (GI) side-effects as compared with sevelamer hydrochloride (SH), because of less expansion of Bix in the GI tract. In this prospective observational study, we evaluated changes in GI symptoms by the Gastrointestinal Symptom Rating Scale (GSRS) score in long-term hemodialysis (HD) outpatients with SH-associated GI symptoms who switched to Bix from SH. A total of 114 patients (age 63.7±10.8 year (mean±SD), female 65.5%, HD vintage 11.2±8.6 years, diabetes mellitus 27.4%) were enrolled. The GSRS score was checked at 0 and 12 weeks after the start of Bix. Bix was started at the initial dose of 750 mg/day, and then was titrated. Serum albumin, P and corrected calcium levels did not significantly change during Bix treatment. However, serum low-density lipoprotein-cholesterol and bicarbonate levels significantly increased during Bix treatment (P<0.001). In GSRS scores, total and domain-specific scores, including constipation, diarrhea, reflux and abdominal pain were significantly reduced at 0, 4, 12 and 24 weeks as compared with those at 0 weeks (P<0.05). This study shows that Bix was well tolerated and managed hyperphosphatemia effectively after switching from SH in Japanese patients on long-term HD. In addition, Bix might be less often associated with GI symptoms as compared with SH.

Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction.

Acute myocardial infarction (MI) causes sterile inflammation, which is characterized by recruitment and activation of innate and adaptive immune system cells. Here we delineate the temporal dynamics of immune cell accumulation following MI by flow cytometry. Neutrophils increased immediately to a peak at 3 days post-MI. Macrophages were numerically the predominant cells infiltrating the infarcted myocardium, increasing in number over the first week post-MI. Macrophages are functionally heterogeneous, whereby the first responders exhibit high expression levels of proinflammatory mediators, while the late responders express high levels of the anti-inflammatory cytokine IL-10; these macrophages can be classified into M1 and M2 macrophages, respectively, based on surface-marker expression. M1 macrophages dominated at 1-3 days post-MI, whereas M2 macrophages represented the predominant macrophage subset after 5 days. The M2 macrophages expressed high levels of reparative genes in addition to proinflammatory genes to the same levels as in M1 macrophages. The predominant subset of dendritic cells (DCs) was myeloid DC, which peaked in number on day 7. Th1 and regulatory T cells were the predominant subsets of CD4(+) T cells, whereas Th2 and Th17 cells were minor populations. CD8(+) T cells, γδT cells, B cells, natural killer (NK) cells and NKT cells peaked on day 7 post-MI. Timely reperfusion reduced the total number of leukocytes accumulated in the post-MI period, shifting the peak of innate immune response towards earlier and blunting the wave of adaptive immune response. In conclusion, these results provide important knowledge necessary for developing successful immunomodulatory therapies.

Clinical significance of IgG deposition in the glomerular mesangial area in patients with IgA nephropathy.

BACKGROUND: Immunoglobulin (Ig) A nephropathy (IgAN) is characterized by mesangial deposits of IgA1 and C3, often with co-deposits of IgG. We attempted to clarify the clinical significance of mesangial IgG deposition in patients with IgAN. METHODS: We retrospectively reviewed 57 patients who were diagnosed with IgAN on the basis of pathological examination of renal biopsy specimens obtained between October 2006 and December 2010. Subjects were divided into two groups: IgA+IgG deposition (IgA-IgG) group (n = 29) and IgA deposition alone (IgA) group (n = 28). The study outcome was complete remission (CR), defined as negative proteinuria by dipstick urinalysis and urinary erythrocytes of less than 1-4/high-power field. RESULTS: Proteinuria was greater in the IgA-IgG group than the IgA group (1.1 ± 0.8 vs. 0.7 ± 0.6 g/day, Mann-Whitney U test, P = 0.042). Capillary wall IgA deposits were noted more frequently in the IgA-IgG group than the IgA group (59 vs. 11 %, Fisher's exact test, P = 0.014). During the median follow-up period of 33.3 months (range 6-55 months) in the 57 patients, we observed CR in 24 cases (42.1 %). After the start of treatment, urinary abnormalities disappeared earlier in the IgA group than in the IgA-IgG group (log rank test, P = 0.012). Cox's regression model showed that IgG deposition reduced the hazard ratio for CR (hazard ratio 0.35; 95 % confidence interval 0.14-0.82, P = 0.014). Therefore, IgG deposition is a risk factor for persistent urinary abnormalities. CONCLUSION: Mesangial IgG deposition is associated with more severe clinical features in patients with IgAN.

[Investigation of cost and medical service fee for pharmaceutical management in home medical care].

Due to the evolvement of the aged society and the steep rise in medical costs, the environment encircling the medical care industry has been changing remarkably. For this reason, it has become both necessary and fundamental for a community pharmacist to participate in home medical care through the pharmaceutical management service. We have studied the associated costs and medical service fees for pharmaceutical management in home medical care. The costs and medical service fees were calculated based on the pharmaceutical management service data collected during the three years from November 1998 to October 2001. As a result, the medical service fees were calculated using the old system which lasted until March 2002. Calculations using this system took into account 550 points per visit, up to two visits per month. Under the new system which started in April 2002, the number of visits taken into account is four times a month, 500 points for the first visit, 300 points from the second through to the forth visit. Then, we simulated a break-even point (BEP). It is clear that it is difficult for any community pharmacy to be specialized in home medical care. In order for the pharmacist to actively participate in home medical care in the future, it is necessary to further improve the system.