Patients with end-stage kidney disease (ESKD) are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity of various trace elements in ESKD patients likely contribute as well. The purpose of this study is to determine the effect of trace elements on statin-induced toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells) for a long time. Cell viability, apoptosis, mRNA expression, and intracellular trace elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity than cells long-time exposed with normal serum (NS cells) (non-overlapping 95% confidence intervals). Intracellular levels of Mg, Mn, Cu, and Zn were significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01). Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated the distinction between both cells of simvastatin-induced cytotoxicity. These results suggest that Zn deficiencies may be involved in the increased risk for muscle complaints in ESKD patients. In conclusion, the increased severity of statin-induced rhabdomyolysis in ESKD patients may be partly due to trace elements deficiencies.
【目的】血液透析患者における，体脂肪量およびその分布と動脈スティッフネスの関連を検討する．【方法】609名の血液透析患者を対象として，上腕―足首間脈波伝播速度（baPWV）を，またdual-energy X-ray absorptiometryにて，体幹，四肢および総脂肪量を測定した．【結果】baPWVは年齢や収縮期血圧と有意な正の相関を認めていた．また，baPWVに男女差は認めなかったが，非糖尿病群に比較して，糖尿病群ではbaPWVは有意に高値であった．重回帰解析において，body mass index，総脂肪量および体脂肪率は，baPWVと有意な関連は認めていなかった．一方，年齢，透析期間，性別，糖尿病の有無，収縮期血圧と独立して，体幹脂肪量は正に，四肢脂肪量は負に，baPWVと有意な関連を認めていた．【結語】血液透析患者において，体幹脂肪は動脈スティッフネスの促進と，四肢脂肪はその抑制と関連している可能性が示唆された．
Acuseal arteriovenous graft is an early cannulation graft having a tri-layered structure with an elastomeric middle layer. However, delamination of Acuseal grafts has been reported recently. This article describes two cases with different characteristics of Acuseal delamination. In case 1, the delamination occurred 1 month after a percutaneous transluminal angioplasty (PTA); therefore, the PTA was suspected to be a trigger. The delamination was located between the outer expanded polytetrafluoroethylene (ePTFE) layer and the elastomeric middle layer. On the other hand, in case 2, the delamination was located between the luminal ePTFE layer and the elastomeric middle layer. A surveillance ultrasound examination detected the delamination unexpectedly in the uneventful course; however, the delaminating location corresponded to the cannulation puncture site and the intraoperative findings suggested the involvement of mis-needling as a possible cause. Interestingly, for the purpose of continued use on hemodialysis, specific treatments were required against the delamination itself in both cases. As we identified Acuseal delamination in 5.6% (2/36) of cases, concerns arise that numerous cases of Acuseal delamination may have been overlooked in general. Understanding and recognizing this phenomenon are important for adequate use of Acuseal graft.
In the present study, the efficacy of sotrovimab and molnupiravir in dialysis patients with COVID-19 was investigated using a registry of COVID-19 in Japanese dialysis patients.Dialysis patients with confirmed SARS-CoV-2 during the COVID-19 (Omicron BA.1 and BA.2) pandemic were analyzed. Patients were classified into four treatment groups: molnupiravir monotherapy (molnupiravir group), sotrovimab monotherapy (sotrovimab group), molnupiravir and sotrovimab combination therapy (combination group), and no antiviral therapy (control group). The mortality rates in the four groups were compared.A total of 1480 patients were included. The mortality of the molnupiravir, sotrovimab, and combination groups were significantly improved compared to the control group (p < 0.001). Multivariate analysis indicated that antiviral therapy improves the survival of dialysis patients with COVID-19 (hazard ratio was 0.184 for molnupiravir, 0.389 for sotrovimab, and 0.254 for combination groups, respectively).Sotrovimab showed efficacy in Omicron BA.1 but attenuated in BA.2. Molnupiravir also showed efficacy in BA.2, suggesting administration of molnupiravir would be important.
Abstract Pharmacokinetics of SN-38 in patients with end-stage kidney disease (ESKD) is partially varied because of fluctuations in transporters expression and/or function by high protein bound-uremic toxins concentration. The fluctuations may induce variations in anticancer drugs sensitivity to cancer cells. We aimed to clarify the variations in sensitivity of SN-38 to cancer patients with ESKD and investigate this mechanism, by human colon cancer cells exposed to uremic serum residue. LS180 cells were exposed to normal or uremic serum residue (LS/NSR or LS/USR cells) for a month. IC 50 values of SN-38 in LS/NSR or LS/USR cells were calculated from viability of each cells treated SN-38. mRNA expression and intracellular SN-38 accumulation was evaluated by RT-PCR and HPLC-fluorescence methods, respectively. The IC 50 value in LS/USR cells was higher than that in LS/NSR cells. Organic anion transporter polypeptide (OATP) 2B1 mRNA expression was lower in LS/USR cells than in LS/NSR cells, and SN-38 accumulation in LS/USR cells was lower than that in LS/NSR cells. Only co-treatment baicalin, which is OATP2B1 inhibitor, almost negated the difference in SN-38 accumulation between LS/NSR and LS/USR. Anticancer effects of substrates of OATP2B1, such as SN-38, were reduced in ESKD patients at the same plasma substrate concentration.
Histamine H2 receptor antagonists (HRA) or proton pump inhibitors (PPI) are frequently administered to patients on hemodialysis, because their intestinal mucosa is fragile. Although three studies have indicated that concomitant HRA administration causes a decrease in the binding of phosphate by calcium carbonate, the HRA doses tested in these studies were 2-4 times higher than the recommended dose for hemodialysis patients. In addition, it remains unclear whether PPI therapy affects serum phosphate levels in hemodialysis patients taking calcium carbonate. Accordingly, the aim of this study was to evaluate the influence of lansoprazole and the recommended dose of famotidine on serum phosphate and calcium levels in hemodialysis patients.The study included 115 hemodialysis patients who were taking calcium carbonate and who were also treated with either famotidine (10 mg/day) or lansoprazole (30 mg/day). Changes of the mean serum phosphate and calcium levels over 2 months before and after the start of famotidine or lansoprazole therapy were compared. The same parameters were also compared when famotidine was switched to lansoprazole.The mean serum phosphate level increased significantly after administration of either famotidine or lansoprazole (by 6.6 +/- 21.9% or 13.0 +/- 26.3%, p = 0.032 and p = 0.029, respectively). The mean serum calcium level was unchanged after administration of famotidine, but showed a significant decrease after administration of lansoprazole (by 3.44 +/- 7.73%, p = 0.013). Therefore, the calcium x phosphorus product was significantly increased by administration of famotidine, but not by administration of lansoprazole (6.68 +/- 23.37% and 8.73 +/- 27.41%, p = 0.046 and p = 0.251, respectively). When famotidine was switched to lansoprazole, the serum phosophate level did not change, but serum calcium decreased significantly by 3.8 +/- 13.0% (p = 0.0006).Not only administration of 20 mg/ day of famotidine as previously reported, but also 10 mg/day of this drug (the recommended dose for hemodialysis patients) caused a significant increase of serum phosphate in patients taking calcium carbonate. PPIs have been reported to show no effect on the serum phosphate level, but 30 mg/day of lansoprazole also caused a significant increase of serum phosphate in patients taking calcium carbonate.
