Association between Timing of Vascular Access Creation and Mortality in Patients Initiating Hemodialysis: A Nationwide Cohort Study in Japan.

INTRODUCTION: The optimal time for vascular access (VA) creation remains controversial. METHODS: We conducted a cohort study using data from the Japanese Society for Dialysis Therapy Renal Data Registry. Adult patients who started receiving hemodialysis in 2007 and had a permanent VA created were included. The exposure of interest was the timing of VA creation, categorized into three groups: early VA creation (defined as creation at least 4 months before hemodialysis initiation), just prior VA creation (creation between 1 and 3 months before hemodialysis initiation), and late VA creation (creation within 1 month of or after hemodialysis initiation). Cox regression analyses were used to compare 1-year all-cause mortality, with late VA creation as the reference group. Owing to the violations of the proportional hazards assumptions, the follow-up period was divided into "early" (1-4 months follow-up) and "late" (5-12 months follow-up) periods. RESULTS: Overall, 1,280 (15.4%) of 8,322 patients died. Both early creation and just prior creation were associated with lower all-cause mortality in the early period compared with late creation. In the late period, the hazard ratios (HRs) for all-cause mortality decreased with earlier VA creation (adjusted HRs [95% confidence intervals]: 0.49 [0.35-0.67] for the early creation group and 0.63 [0.51-0.79] for the just prior creation group). CONCLUSION: Our study suggests that VA creation at least 1 month before hemodialysis initiation is associated with lower all-cause mortality in the early period, with earlier VA creation resulting in further mortality reduction in the late period.

Cellular and humoral immune responses to COVID-19 booster vaccination in Japanese dialysis patients.

BACKGROUND: Dialysis patients are susceptible to developing severe coronavirus disease 2019 (COVID-19) due to hypoimmunity. Antibody titers against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) after the primary vaccinations are lower in hemodialysis (HD) patients than in healthy individuals. This study aimed to evaluate the effect of a SARS-CoV-2 booster vaccination in HD and peritoneal dialysis (PD) patients based on antibody titers and cellular and humoral immunity. METHODS: Participants of the control, HD, and PD groups were recruited from 12 facilities. SARS-CoV-2 antigen-specific cytokine and IgG-antibody levels were measured. Regulatory T cells and memory B cells were counted using flow cytometry at 6 months after primary vaccination with BNT162b2 and 3 weeks after the booster vaccination in HD and PD patients and compared with those of a control group. RESULTS: Booster vaccination significantly enhanced the levels of antibodies, cytokines, and memory B cells in three groups. The HD group showed significantly higher levels of IgG-antibodies, IL-1ß, IL-2, IL-4, IL-17, and memory B cells than those in the control group at 3 weeks after the booster dose. The PD group tended to show similar trends to HD patients but had similar levels of IgG-antibodies, cytokines, and memory B cells to the control group. CONCLUSIONS: HD patients had significantly stronger cellular and humoral immune responses than the control 3 weeks after the booster dose. Our findings will help in developing better COVID-19 vaccination strategies for HD and PD patients.

Coronavirus disease 2019 vaccination effectiveness based on the 2021 Japanese dialysis registry.

AIM: The effectiveness of the coronavirus disease (COVID-19) vaccine in Japanese patients undergoing haemodialysis has previously not been evaluated on a large scale. We analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR), covering nearly all Japanese patients undergoing dialysis (~95% coverage), to examine the association between COVID-19 vaccination and infection or mortality. METHODS: We used data from the JRDR end-of-year surveys conducted in 2020 and 2021, including information on the COVID-19 vaccination and infection months. COVID-19 infection incidence and its associated mortality rates based on vaccination status (time updated) and odds ratio (OR) (vaccinated vs. unvaccinated) were estimated monthly from April 2021, when vaccination commenced in Japan. RESULTS: COVID-19 infection analysis included 228 865 patients (215 941 vaccinated and 12 924 unvaccinated patients at the end of 2021). The age- and sex-adjusted ORs (aORs) were significantly lower in August, September, October and November 2021, especially in September (aOR [95% confidence interval (CI)]: 0.25 [0.18-0.36]). Additional adjustments for past medical history and laboratory results rarely affected these results. Similarly, in the COVID-19-related mortality analysis with 228 731 patients, including 216 781 vaccinated and 11 950 unvaccinated at the end of 2021, COVID-19-related mortality risk was significantly lower in the vaccinated group in August, September, October and November (aOR [95% CI]: August, 0.32 [0.12-0.84], September, 0.04 [0.01-0.11]; October, 0.10 [0.01-0.81]; November, 0.05 [0.00-0.79]). CONCLUSION: In Japanese patients undergoing haemodialysis, the first or second COVID-19 vaccine dose was significantly associated with decreased COVID-19 infection and mortality rates, suggesting its effectiveness in this population.

Association of Four Types of Vascular Access Including Arterial Superficialization with Mortality in Maintenance Hemodialysis Patients: A Nationwide Cohort Study in Japan.

INTRODUCTION: Vascular access usage varies widely across countries. Previous studies have evaluated the association of clinical outcomes with the three types of vascular access, namely, arteriovenous fistula (AVF), arteriovenous graft (AVG), and tunneled and cuffed central venous catheter (TC-CVC). However, little is known regarding the association between arterial superficialization (AS) and the mortality of patients. METHODS: A nationwide cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry (2006-2007). We included patients aged ≥20 years undergoing hemodialysis with a dialysis vintage ≥6 months. The exposures of interest were the four types of vascular access: AVF, AVG, AS, and TC-CVC. Cox proportional hazard models were used to evaluate the associations of vascular access types with 1-year all-cause and cause-specific mortality. RESULTS: A total of 183,490 maintenance hemodialysis patients were included: 90.7% with AVF, 6.9% with AVG, 2.0% with AS, and 0.4% with TC-CVC. During the 1-year follow-up period, 13,798 patients died. Compared to patients with AVF, those with AVG, AS, and TC-CVC had a significantly higher risk of all-cause mortality after adjustment for confounding factors: adjusted hazard ratios (95% confidence intervals) - 1.30 (1.20-1.41), 1.56 (1.39-1.76), and 2.15 (1.77-2.61), respectively. Similar results were obtained for infection-related and cardiovascular mortality. CONCLUSION: This nationwide cohort study conducted in Japan suggested that AVF usage may have the lowest risk of all-cause mortality. The study also suggested that the usage of AS may be associated with better survival rates compared to those of TC-CVC in patients who are not suitable for AVF or AVG.

Factors associated with SARS-CoV-2 antibody titers and prognosis of breakthrough infection in hemodialysis patients.

BACKGROUND: The mortality rate of Coronavirus disease 2019 (COVID-19) is extremely high in hemodialysis patients (HDP). These patients also develop lower antibody titers after vaccination. Therefore, factors associated with antibody titers and vaccine efficacy in HDP with breakthrough infection need to be investigated. METHODS: We measured anti-S1 antibody titers in HDP (n = 104) and controls (n = 35), evaluating the influence of background on HDP by multivariable regression analysis. We classified 26 HDP patients admitted with COVID-19 into the unvaccinated (n = 15) and breakthrough infection group (n = 11), performing between-group comparisons of laboratory findings and prognosis. Vaccinated COVID-19 patients were classified into HDP and non-HDP controls, and compared the relationship between antibody titer and severity, and the prognosis of breakthrough infection. RESULTS: The antibody titer was significantly lower in the HDP group than in the control group. Among HDP, age and smoking history were significantly independent factors associated with antibody titer. The breakthrough infection group had significantly better laboratory findings (KL-6 and LDH), severity, and hospitalization period than the unvaccinated group even if antibody titers were lower than the known threshold for neutralization (p < 0.05). There was no significant difference in prognosis between the HDP and non-HDP with breakthrough infection. Severity of COVID-19 tended to be higher with lower antibody titer in non-HDP, but not in HDP. CONCLUSION: Vaccines improved the severity of COVID-19 and hospitalization period of breakthrough infection in HDP, although HDP, especially in elderly smokers had lower antibody titers than control. There was no significant association between antibody titer and severity in HDP.

Utility of serological tumor biomarkers for surveillance of hepatocellular carcinoma in patients undergoing dialysis.

BACKGROUND: Patients undergoing dialysis are at risk of hepatocellular carcinoma (HCC) and preferably should undergo HCC surveillance. We investigated the utility of HCC tumor markers for HCC surveillance in patients undergoing dialysis. METHODS: Three serum markers specific for HCC, namely alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), were measured in dialysis patients with and without a diagnosis of HCC (n = 60 and 507, respectively). The predictive value of each marker and that of a diagnostic score (GALAD score) based on patient age and gender as well as the same three markers were evaluated by receiver-operating characteristic (ROC) analysis, as well as sensitivity and specificity. RESULTS: AFP, DCP and the GALAD scores showed high predictive values for HCC, with areas under the ROC curve of >0.85. This effectiveness remained when focusing on small HCC (≤3 cm or ≤2 cm) or early-stage HCC (Stage I), as well as after propensity score matching of background characteristics of HCC and non-HCC patients. In particular, DCP and GALAD score had excellent predictive abilities for HCC. CONCLUSIONS: Measuring serum tumor markers for HCC can serve as a complement to imaging studies in the surveillance of HCC in patients undergoing dialysis, and reduce the likelihood of advanced HCC at detection and diagnosis.

Nationwide survey of the coronavirus disease 2019 prevention and treatment systems for kidney disease patients: a study of Japanese Society of Nephrology-certified educational facilities.

BACKGROUND: There are no reports of a large-scale survey on the infection prevention measures against coronavirus disease 2019 (COVID-19) in nephrology facilities. This study investigated the facility-level nephrology practices adopted during the COVID-19 pandemic and their associated challenges. Additionally, the treatment patterns and outcomes of chronic kidney disease (CKD) patients with COVID-19 were reviewed. METHODS: We conducted a nationwide questionnaire survey of 704 educational facilities that were certified by the Japanese Society of Nephrology (JSN) from October 20, 2020 to November 16, 2020. The questionnaire reviewed the facility characteristics, infection prevention measures taken during routine nephrology practice, impact of COVID-19 on nephrology practice, experiences in managing CKD patients with COVID-19, and nosocomial transmission in the nephrology unit. RESULTS: Of the 347 facilities that responded, 95.1% checked outpatients' body temperatures and COVID-19 symptoms at their visits. To reduce face-to-face contact, 80% and 70% of the facilities lengthened the intervals between outpatient visits and introduced online/telephonic consultations, respectively. As a result, more than half of the hospitals experienced a decrease in the numbers of outpatients and inpatients (64% and 50%, respectively). During the study period, 347 facilities managed 479 CKD patients with COVID-19. Oxygen administration and mechanical ventilation were performed for 47.8% and 16.5% of the patients, respectively, with a 9.2% total mortality rate. CONCLUSION: This survey demonstrated that JSN-certified educational nephrology facilities adopted multiple measures to manage the COVID-19 pandemic; however, they faced several challenges. Sharing these experiences could standardize these approaches and prepare us better for the future.

Predilution online hemodiafiltration is associated with improved survival compared with hemodialysis.

On-line hemodiafiltration is an increasingly common alternative to chronic hemodialysis in some countries, based on the results of randomized controlled trials of post-dilution on-line hemodiafiltration. There are now more than 60,000 patients treated with on-line hemodialfiltration in Japan, over 95% of whom use predilution on-line hemodiafiltration; however, large-scale data on clinical outcomes with this modality are lacking. We created a propensity-matched cohort of 5,000 pairs of patients treated with conventional hemodialysis or predilution on-line hemodiafiltration, using the Japanese Society for Dialysis Therapy Renal Data Registry database from December 31, 2012 to December 31, 2013. One-year all-cause and cardiovascular mortality were compared between the groups. Predilution on-line hemodiafiltration was associated with improved overall survival compared to hemodialysis (hazard ratio for all cause-mortality 0.83, 95% confidence interval 0.705-0.986), with a trend towards improved cardiovascular survival. Among patients treated with predilution on-line hemodiafiltration, those treated with high substitution volumes (≥40.0 L per session) had improved all-cause and cardiovascular survival compared to those treated with low substitution volumes (<40.0 L per session) or those on hemodialysis. The optimal substitution volume associated with improved overall survival was estimated to be 50.5 L [95% confidence interval 39.0-63.5 L]. This observational study suggests that predilution on-line hemodiafiltration, especially with high substitution volumes, may improve all-cause and cardiovascular survival, but randomized controlled trials are needed.

Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan.

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

Superior Rhythm Discrimination With the SmartShock Technology Algorithm　- Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial.

BACKGROUND: Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology®(SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). CONCLUSIONS: Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.

Current dialyzer classification in Japan and mortality risk in patients undergoing hemodialysis.

Dialyzers are classified into five types based on their ß2-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a ß2-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis.Trial registration number: UMIN000018641.

Molecular ablation of ventricular tachycardia after myocardial infarction.

Ventricular tachycardia is a common and lethal complication after myocardial infarction. Here we show that focal transfer of a gene encoding a dominant-negative version of the KCNH2 potassium channel (KCNH2-G628S) to the infarct scar border eliminated all ventricular arrhythmias in a porcine model. No proarrhythmia or other negative effects were discernable. Our results demonstrate the potential viability of gene therapy for ablation of ventricular arrhythmias.

Effects of cinacalcet on bone mineral density and bone markers in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: Cinacalcet markedly reduces the serum intact parathyroid hormone (PTH) level of hemodialysis (HD) patients with secondary hyperparathyroidism. Parathyroidectomy also reduces the serum intact PTH level of HD patients and it increases their bone mineral density (BMD). However, there is little information about the effect of cinacalcet on BMD or on the associations between bone markers and BMD in HD patients. METHODS: We performed a 1-year cohort study of 25 HD patients who had a serum intact PTH level above 300 pg/ml during treatment by conventional therapies, such as with active vitamin D, and cinacalcet was prescribed for 14 of them. BMD of the femoral neck and the serum levels of two circulating bone markers, alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BSAP), were measured before and after treatment. The other 11 HD patients without cinacalcet treatment were defined as control group. RESULTS: BMD significantly increased by 7.3 % during the 1 year of treatment in the cinacalcet group and decreased by 6.2 % during the same period in the control group, and cinacalcet therapy was independently associated with the changes in BMD after multiple regression analysis that included intact PTH (ß = 7.57, P < 0.01). In the cinacalcet group, the serum ALP levels (R(2) = 0.315, P < 0.05) and BSAP levels (R(2) = 0.682, P < 0.01) levels were significantly negatively correlated with the changes in BMD, but the serum intact PTH levels were not significantly associated with the changes in BMD (R(2) = 0.011, P = 0.72). CONCLUSIONS: One year of treatment with cinacalcet increased the BMD of the femoral neck in the HD cohort, especially in the patients who had higher serum ALP and BSAP levels at baseline.

The Impact and Treatment of COVID-19 in Hemodialysis Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) undergoing maintenance hemodialysis have a poor prognosis and limited treatment options. METHODS: This paper outlines the impact of COVID-19, its treatment, and the efficacy of vaccines in Japanese patients undergoing hemodialysis with a review of the literature. RESULTS: Patients undergoing dialysis in dialysis facilities are at greater risk of exposure to severe acute respiratory syndrome coronavirus 2 than the general population due to limited isolation capabilities. Therefore, vaccines are expected to be effective for patients undergoing dialysis. In addition, effective use of available medications is important because treatment options are limited. CONCLUSIONS: Efforts should be made to prevent the spread of the infection to high-risk patients undergoing dialysis while ensuring the effective use of vaccines.

Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy.

The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.

Effectiveness of SARS-CoV-2 vaccines on hemodialysis patients in Japan: A nationwide cohort study.

INTRODUCTION: This study compared the outcomes of dialysis patients who received SARS-CoV-2 vaccine with those who did not use data from the Japanese COVID-19 registry. METHODS: A total of 1260 dialysis patients with confirmed positive SARS-CoV-2 infection was included in this study. Patients were divided into two groups: patients who experienced breakthrough infection and those who were unvaccinated. The need of oxygen supplementation and mortality risks were compared using multivariate logistic regression analysis. RESULTS: The mortality rate was 24.2% in unvaccinated patients and 8.6% in breakthrough patients. The odds ratio of need of oxygen supplementation in the breakthrough patients relative to unvaccinated patients was 0.197. The hazard ratio of mortality in the breakthrough patients relative to unvaccinated patients was 0.464. CONCLUSION: Our prospective observational study showed that SRAS-CoV-2 vaccination in hemodialysis patients is vital for reducing need of oxygen supplementation and mortality risk.

Cellular and Humoral Immune Responses after Breakthrough Infection in Patients Undergoing Hemodialysis.

Coronavirus disease 2019 (COVID-19) following primary immunization (breakthrough infection) has been reported in hemodialysis patients; however, their post-infection immune status remains unclear. We evaluated the humoral and cellular immunity of hemodialysis patients after breakthrough infection. Hemodialysis patients who had received primary immunization against COVID-19 at least six months prior to the study but developed mild/moderate COVID-19 before a booster dose (breakthrough infection group) and hemodialysis patients who were not infected with COVID-19 but received a booster dose (booster immunization group) were recruited. In both groups, SARS-CoV-2 antigen-specific cytokines and IgG levels were measured three weeks after infection or three weeks after receiving a booster dose. Memory T and B cells were also counted in the breakthrough infection group using flow cytometry three weeks after infection. Significantly higher SARS-CoV-2 antigen-specific IgG, IFN-γ, IL-5, TNF-α, and IL-6 levels occurred in the breakthrough infection group compared to the booster immunization group (p = 0.013, 0.039, 0.024, 0.017, and 0.039, respectively). The SARS-CoV-2 antigen-specific IgG and cytokine levels were not significantly different between the two groups. The breakthrough infection group had significantly higher percentages of central and effector memory T cells and regulatory T cells than the comparison group (p = 0.008, 0.031, and 0.026, respectively). Breakthrough infections may induce stronger cellular and humoral immune responses than booster immunizations in hemodialysis patients.

Efficacy of molnupiravir and sotrovimab in Japanese dialysis patients with COVID-19 in clinical practice during the Omicron (BA.1 and BA.2) pandemic.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.