Committee report : Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy

Background: Patients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis. Methods: A questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021. Results: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities. Conclusions: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy

Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group

Long-Term Safety and Efficacy of JR-131, a Biosimilar of Darbepoetin Alfa, in Japanese Patients With Renal Anemia Undergoing Hemodialysis: Phase 3 Prospective Study

The objective of this study was to evaluate the safety and efficacy of JR-131, a biosimilar of darbepoetin alfa, for long-term treatment of renal anemia patients undergoing hemodialysis. In this multicenter, single-arm, phase 3 study, 159 patients with renal anemia who had been receiving darbepoetin alfa or recombinant human erythropoietins were treated with intravenous JR-131 for 52 weeks. In patients receiving darbepoetin alfa, JR-131 was administered at the same dose, while in patients receiving recombinant human erythropoietin the dose was determined based on the 1:200 conversion ratio following the Japanese darbepoetin alfa package insert. No notable adverse drug reactions were reported, and no anti-JR-131 antibodies were detected. The hemoglobin levels were maintained in the range of 10.0-12.0 g/dL throughout the study. JR-131 proved to be a useful and lower-cost alternative to darbepoetin alfa in the management of renal anemia in patients undergoing hemodialysis

Nalfurafine hydrochloride for refractory pruritus in peritoneal dialysis patients: a phase III, multi-institutional, non-controlled, open-label trial

Abstract Background Nalfurafine hydrochloride (“nalfurafine”), the world’s first selective oral κ-receptor agonist for improving pruritus, is approved in Japan for the treatment of pruritus resistant to existing treatments in hemodialysis (HD) or chronic liver disease patients. Peritoneal dialysis (PD) patients, like HD patients, suffer from end-stage renal disease (ESRD) and some experience refractory pruritus. Methods We investigated the efficacy and safety of nalfurafine in 37 ESRD patients who underwent PD and had refractory pruritus. Nalfurafine was given once daily for 4 weeks at 2.5 μg in weeks 1 and 2 of the treatment period and at 5 μg in weeks 3 and 4. The primary endpoint was visual analog scale (VAS) changes for pruritus (i.e., the value upon rising or before sleep in week 2, whichever larger). Results The mean VAS change from baseline in week 2 of the treatment period was 24.93 mm [18.67, 31.19] (the point estimate of the mean [90% confidence interval (CI)]); the lower limit of CI exceeded the point estimate of the mean VAS change (15.24 mm) of the placebo group at the evaluation point (week 2) in a preceding confirmatory trial suggesting that had demonstrated nalfurafine efficacy for refractory pruritus in HD patients. The observed VAS change was comparable to that of the 2.5-μg group (week 2) in the preceding confirmatory trial, demonstrating that nalfurafine is as effective for treating pruritus in PD patients as in HD patients. Nalfurafine 5 μg was associated with a mean VAS change of 32.13 mm at week 4, i.e., the full length of the trial treatment period suggesting efficacy at the dose of 5 μg. The incidence of adverse drug reactions (ADR) was 45.9% (1/37 patients) with no serious ADRs observed. ADRs occurring in ≥ 5% of patients included insomnia (13.5%), increased blood prolactin (13.5%), somnolence (8.1%), lower blood testosterone free (8.1%), and vomiting (5.4%), all of which were mild. Conclusions This trial demonstrated the efficacy and safety of nalfurafine against refractory pruritus in PD, suggesting clinical benefit for treating pruritus in PD patients. Trial registration Japan Pharmaceutical Information Center, JapicCTI-14256

Does Improvement in Health-Related Lifestyle Habits Increase Purpose in Life among a Health Literate Cohort?

A growing number of studies have revealed the association between health-related lifestyle habits and purpose in life. However, the mechanism linking the two has not been adequately understood. This study aims to examine the effect of changes in health-related lifestyle habits on purpose in life. A retrospective cohort study was conducted on certified professional specialists of health management. We analyzed the cohort&rsquo;s demographic information, health-related lifestyle behaviors, reported changes in health-related lifestyle habits (exercise, diet, sleep, and other habits), and purpose in life using a validated tool (Ikigai-9). The cohort was divided into four groups based on the number of reported changes in health-related lifestyles. The purpose in life score was compared among the four groups with and without adjusting for lifestyle. In total, there were 4820 participants. The means (and SD) of the Ikigai-9 score for groups 1, 2, 3, and 4 were 31.4 (6.6), 32.2 (5.6), 32.8 (5.8), and 34.9 (5.4), respectively. There was a statistically significant difference in the Ikigai-9 score among the groups. Healthier changes in lifestyle habits increased perceptions of purpose in life. Both purpose in life and health-related lifestyle habits might be the target factors for disease prevention and health promotion