Evaluation of switching treatment from high dose of darbepoetin to lower dose of roxadustat in Japanese hemodialysis patients.

Roxadustat is one of the oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) that stimulates erythropoiesis and regulates the genes related to iron metabolism. The treatment of HIF-PHIs is useful compared with that of erythropoietin stimulating agent (ESA) using various instruments and procedures. Few clinical researchers have examined the efficacy and safety of switching treatment from Darbepoetin to Roxadustat in Japanese hemodialysis (HD) patients. However, HIF-PHIs have severe adverse drug reactions, such as thrombotic events. In the present study, we evaluated the lower dose of roxadustat in HD patients receiving high dose of ESA therapy. Eighteen anemic HD patients receiving an ESA, that is,, darbepoetin over 40 µg per week, were enrolled in this study. The treatment of these patients was changed to 20 mg of roxadustat three times weekly for 6 months, after which doses were adjusted to achieve a hemoglobin (Hb) target of 10.0-12.0 g/dL. An increase of 58.1 ± 32.5 mg roxadustat three times weekly increased Hb. It also achieved and then maintained levels within the target range at month 6. Ferritin levels of more than 100 ng/mL or TSAT levels of more than 20% were maintained during the 6-month treatment periods with oral or intravenous iron supplementation. It seems unnecessary to increase the initial dose of roxadustat for patients using high doses of ESA. It is suggested that a reconsideration of the starting dose of roxadustat in Japanese HD patients is needed. (Ikegami General Hospital, Medical Corporation SHOWAKAI、Approval number: 2020-4).

Effects of L-Carnitine Supplementation in Patients Receiving Hemodialysis or Peritoneal Dialysis.

L-carnitine is an important factor in fatty acid metabolism, and carnitine deficiency is common in dialysis patients. This study evaluated whether L-carnitine supplementation improved muscle spasm, cardiac function, and renal anemia in dialysis patients. Eighty Japanese outpatients (62 hemodialysis (HD) patients and 18 peritoneal dialysis (PD) patients) received oral L-carnitine (600 mg/day) for 12 months; the HD patients further received intravenous L-carnitine injections (1000 mg three times/week) for 12 months, amounting to 24 months of treatment. Muscle spasm incidence was assessed using a questionnaire, and cardiac function was assessed using echocardiography. Baseline free carnitine concentrations were relatively low in patients who underwent dialysis for >4 years. Total carnitine serum concentration, free carnitine, and acylcarnitine significantly increased after oral L-carnitine treatment for 12 months, and after intravenous L-carnitine injection. There was no significant improvement in muscle spasms, although decreased muscle cramping after L-carnitine treatment was reported by 31% of patients who had undergone HD for >4 years. Hemoglobin concentrations increased significantly at 12 and 24 months in the HD group. Therefore, L-carnitine may be effective for reducing muscle cramping and improving hemoglobin levels in dialysis patients, especially those who have been undergoing dialysis for >4 years.

Oral Astaxanthin Supplementation Prevents Peritoneal Fibrosis in Rats.

BACKGROUND: Preventing peritoneal damage during peritoneal dialysis is critical. Reactive oxygen species (ROS) have an important role in peritoneal damage; however, few studies have investigated this. We aimed to determine the effects of oral astaxanthin (AST) supplementation in a peritoneal fibrosis (PF) rat model. METHODS: Thirty-seven Sprague-Dawley rats were divided into 5 groups: Control 1 (fed a normal diet without stimulation), Control 2 (fed an AST-supplemented diet without stimulation), Group 1 (fed a normal diet with 8% chlorhexidine gluconate [CG] stimulation for 3 weeks), Group 2 (fed a 0.06% AST-supplemented diet with CG stimulation), and Group 3 (fed a 0.06% AST-supplemented diet that was initiated 4 weeks before CG stimulation). Peritoneal fibrosis, vascular proliferation, and fibrosis-related factor expression were examined. RESULTS: Peritoneal thickness was significantly suppressed by AST supplementation. Astaxanthin diminished the number of CD68-, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-, and monocyte chemoattractant protein-1 (MCP-1)-positive cells. Type 3 collagen, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and MCP-1 mRNA expression was significantly lower in Group 3 than in Group 1. Increased transforming growth factor-ß (TGF-ß) and Snail mRNA expression, vascular density, and the number of α-smooth muscle actin (α-SMA)-positive cells were also decreased in Group 3. CONCLUSION: Astaxanthin suppressed PF development through the inhibition of inflammation and oxidation in PF rats. It appears that the anti-oxidative agent AST may be useful for the prevention of peritoneal damage.