Effects of switching from sevelamer hydrochloride to bixalomer on laboratory parameters in hemodialysis patients.

In Japan, the clinical use of bixalomer, a new polymer preparation like sevelamer hydrochloride, became possible from 2012. In our study, in order to investigate the clinical characteristics of this new phosphorus (P) binder, bixalomer in a clinical practice, for 18 cases of hemodialysis patients at our hospital being treated with sevelamer hydrochloride, we switched the P binder to bixalomer, and compared the laboratory parameters before and after switching. Subjects used for analysis were nine cases in which it was possible to use bixalomer continuously for 10 months. The laboratory parameters measured were the concentrations of serum P, corrected calcium (Ca), whole parathyroid hormone (PTH), albumin and alkaline phosphatase (ALP) as indicators of mineral and bone disorder, and serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) as indicators of lipid metabolism. Regarding the results after switching to bixalomer and starting treatment using the same dosage as the dosage previously used for sevelamer hydrochloride, there were many cases that showed increasing P concentrations that required increasing the dosage of bixalomer, the dosage after switching was increased significantly (P=0.002). In the comparison of laboratory parameters before and after switching, the concentrations of serum P and albumin decreased significantly (P=0.035 and 0.033). From these results, it was considered that the decreases in serum P concentrations were due not only to the effects of bixalomer, but that suppression of food intake by patients was another reason. There were no significant changes in corrected Ca, whole PTH or ALP. In addition, after changing the P binder, serum HDL-C concentration decreased significantly (P=0.015) and LDL-C increased significantly (P<0.001), and serum TG concentration showed no significant changes. This indicated that the beneficial effects of bixalomer on lipid metabolism may be less than those of sevelamer hydrochloride.

Combination of TLC blotting and gas chromatography-mass spectrometry for analysis of peroxidized cholesterol.

We have established a sensitive and convenient method for analysis of cholesterol hydroperoxides (Chol-OOHs) as trimethylsilyloxyl derivatives using diphenylpyrenylphosphine (DPPP)-thin-layer chromatography (TLC) blotting and gas chromatography-electron ionization-mass spectrometry/selected-ion monitoring (GC-EI-MS/SIM). Chol-OOH standards were prepared by photosensitized oxidation and azo radical-induced peroxidation of cholesterol. Trimethylsilyloxyl derivatives of cholesterol 5alpha-hydroperoxide (Chol 5alpha-OOH), cholesterol 7alpha-hydroperoxide (Chol 7alpha-OOH), and cholesterol 7beta-hydroperoxide (Chol 7beta-OOH) could be separated from one another in the SIM chromatogram using a fragment ion with elimination of trimethylsilanol from the molecular ion. This method was used to characterize peroxidized cholesterol from azo radical-exposed human low-density lipoprotein and UVA-irradiated human keratinocytes in the presence of hematoporphyrin. Finally, we succeeded in the quantification of each Chol-OOH isomer present in hairless mouse skin with and without UVA irradiation by use of beta-sitosterol hydroperoxide as internal standard. The accumulation of Chol 5alpha-OOH with Chol 7alpha/betaOOH in the skin indicates that singlet molecular oxygen ((1)O(2)) participated in the peroxidation of skin cholesterol, because Chol 5alpha-OOH is known to be a (1)O(2) specific cholesterol peroxidation product. We concluded that the combination of DPPP-TLC blotting and GC-EI-MS/SIM is useful for quantifying peroxidized cholesterol in biological samples and confirming the participation of (1)O(2) in oxidative stress.