Immunogenicity and safety of COVID-19 BNT162b2 booster vaccine in end-stage kidney disease patients receiving haemodialysis in Yogyakarta, Indonesia: a cohort prospective study.

BACKGROUND: A significant decrease in antibody titres several months after COVID-19 primary vaccination in end-stage kidney disease (ESKD) patients receiving maintenance haemodialysis has recently been reported. The waning in antibody titres has led to the recommendations for a booster dose to increase the antibody titres after vaccination. Consequently, it is crucial to analyse the long-term humoral immune responses after COVID-19 primary vaccination and assess the immunogenicity and safety of booster doses in haemodialysis (HD) patients. METHODS: Patients on maintenance haemodialysis who received the primary vaccine of CoronaVac (Sinovac) vaccine were administered with BNT162b2 (Pfizer-BioNTech) as the booster dose. The immunogenicity was assessed before (V1), one month (V2) and eight months (V3) after the primary vaccination, as well as one month after the booster dose (V4). Patients were followed up one month after the booster dose to assess the adverse events (AEs). RESULTS: The geometric mean titre (GMT) of anti-SARS-CoV-2 S-RBD IgG antibody at 8 months after the primary vaccination increased significantly to 5,296.63 (95%CI: 2,930.89-9,571.94) U/mL (p = < 0.0001) compared to before the primary vaccination. The GMT also increased significantly to 19,142.56 (95% CI: 13,489.63-27,227.01) U/mL (p < 0.0001) 1 month after the booster vaccine. Meanwhile, the median inhibition rate of neutralizing antibodies (NAbs) at 8 months after the primary vaccine and 1 month after the booster dose were not significantly different (p > 0.9999). The most common AEs after the booster dose included mild pain at the injection site (55.26%), mild fatigue (10.53%), and swelling at the injection site (10.53%). No serious AEs were reported. CONCLUSIONS: The majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events.

Projecting the future: modelling Australian dialysis prevalence 2021-30.

Objectives To project the prevalence of people receiving dialysis in Australia for 2021-30 to inform service planning and health policy. Methods Estimates were based on data from 2011 to 2020 from the Australia & New Zealand Dialysis & Transplant (ANZDATA) Registry and the Australian Bureau of Statistics. We projected dialysis and functioning kidney transplant recipient populations for the years 2021-30. Discrete-time, non-homogenous Markov models were built on probabilities for transition between three mutually exclusive states (Dialysis, Functioning Transplant, Death), for five age groups. Two scenarios were employed - stable transplant rate vs a continued increase - to assess the impact of these scenarios on the projected prevalences. Results Models projected a 22.5-30.4% growth in the dialysis population from 14 554 in 2020 to 17 829 ('transplant growth') - 18 973 ('transplant stable') by 2030. An additional 4983-6484 kidney transplant recipients were also projected by 2030. Dialysis incidence per population increased and dialysis prevalence growth exceeded population ageing in 40-59 and 60-69 year age groups. The greatest dialysis prevalence growth was seen among those aged ≥70 years. Conclusion Modelling of the future prevalence of dialysis use highlights the increasing demand on services expected overall and especially by people aged ≥70 years. Appropriate funding and healthcare planning must meet this demand.

Gastrointestinal manifestations of long-term effects after COVID-19 infection in patients with dialysis or kidney transplantation: An observational cohort study.

BACKGROUND: Prolonged symptoms after corona virus disease 2019 (Long-COVID) in dialysis-dependent patients and kidney transplant (KT) recipients are important as a possible risk factor for organ dysfunctions, especially gastrointestinal (GI) problems, during immunosuppressive therapy. AIM: To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status. METHODS: This observational, prospective study included patients with COVID-19 infection, confirmed by reverse transcription polymerase chain reaction, with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset, either through the out-patient follow-up or by telephone interviews. RESULTS: The 645 eligible participants consisted of 588 cases with hemodialysis (HD), 38 patients with peritoneal dialysis (PD), and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these, 577 (89.5%) cases agreed to the interviews, while 64 (10.9%) patients with HD and 4 (10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups, respectively, and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524 (56%) and 21/34 (62%) in HD and PD, respectively, and 7/19 (37%) KT recipients. Fatigue was the most prevalent (96%) of the non-GI tract symptoms, whereas anorexia (90.9%), loss of taste (64.4%), and abdominal pain (62.5%) were the first three common GI manifestations of Long-COVID. Notably, there were 6 cases of mesenteric panniculitis from 19 patients with GI symptoms in the KT group. CONCLUSION: Different from patients with non-chronic kidney disease, there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.

What data collection methods work best for COVID19 outbreak surveillance for people with end stage kidney disease? An observational cohort study using the UK Renal Registry.

BACKGROUND: Patients on kidney replacement therapy (KRT) are vulnerable to severe illness from COVID-19. Timely, accurate surveillance is essential for planning and implementing infection control at local, regional and national levels. Our aim was to compare two methods of data collection for COVID-19 infections amongst KRT patients in England. METHODS: Adults receiving KRT in England were linked to two sources of data on positive COVID-19 tests recorded March-August 2020: (1) submissions from renal centres to the UK Renal Registry (UKRR) and (2) Public Health England (PHE) laboratory data. Patient characteristics, cumulative incidence by modality (in-centre haemodialysis (ICHD), home HD, peritoneal dialysis (PD) and transplant), and 28-day survival were compared between the two sources. RESULTS: 2,783/54,795 patients (5.1%) had a positive test in the combined UKRR-PHE dataset. Of these 2,783, 87% had positive tests in both datasets. Capture was consistently high for PHE (> 95% across modalities) but varied for UKRR (ranging from ICHD 95% to transplant 78%, p < 0.0001). Patients captured only by PHE were more likely to be on transplant or home therapies (OR 3.5 95% CI [2.3-5.2] vs. ICHD) and to be infected in later months (OR 3.3 95%CI [2.4-4.6] for May-June, OR 6.5 95%CI [3.8-11.3] for July-August, vs. March-April), compared to patients in both datasets. Stratified by modality, patient characteristics and 28-day survival were similar between datasets. CONCLUSIONS: For patients undergoing ICHD treatment the collection of data submitted directly by renal centres allows constant monitoring in real time. For other KRT modalities, using a national swab test dataset through frequent linkage may be the most effective method. Optimising central surveillance can improve patient care by informing interventions and assisting planning at local, regional and national levels.

Effect of Lymphocyte Phenotypic Alterations on the Humoral Response to Vaccination Against SARS-COV-2 in Dialysis Patients.

Background: The response to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies depending on comorbidities. This study evaluated the clinical and immunological factors affecting the humoral response of patients with end-stage renal disease (ESRD) to the BNT162b2 vaccine. Methods: Humoral immunity was evaluated in 54 ESRD patients using serum levels of anti-receptor-binding domain (RBD) and neutralizing antibodies (NAbs), measured by a chemiluminescent immunoassay 30 (T1), 60 (T2), and 120 (T3) days after the second vaccine dose. The results were correlated to baseline patient T- and B-lymphocyte subpopulations determined by flow cytometry. Results: The proportion of seroconverted patients based on the NAb titer decreased from 83.3% at T1 to 53.7% at T3. Age was negatively correlated to the NAb titer at T1 and T2. Patients receiving hemodiafiltration had higher NAb titers at T3. Diabetes was associated with a lower response rate at T3. Univariate analysis revealed a positive correlation between the naïve CD4 T-lymphocyte population and RBD titer at T1 and the NAb titer at T3, with no association observed with naïve CD8 T lymphocytes. NAb titers at T3 were significantly correlated with late-differentiated CD4 T lymphocytes and terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 T lymphocytes. RBD levels were positively correlated with naïve and memory B-lymphocyte counts at T3. Conclusions: Age, diabetes, and hemodialysis prescription had significant impacts on the response to vaccination. T- and B-lymphocyte phenotypes are major determinants of the humoral response potency to SARS-CoV-2 vaccination with BNT162b2 in patients with ESRD.

Platelet-albumin-bilirubin score and neutrophil-to-lymphocyte ratio predict intensive care unit admission in patients with end-stage kidney disease infected with the Omicron variant of COVID-19: a single-center prospective cohort study.

OBJECTIVES: The objective of this study was to develop clinical scores to predict the risk of intensive care unit (ICU) admission in patients with COVID-19 and end stage kidney disease (ESKD). METHODS: This was a prospective study in which 100 patients with ESKD were enrolled and divided into two groups: the ICU group and the non-ICU group. We utilized univariate logistic regression and nonparametric statistics to analyze the clinical characteristics and liver function changes of both groups. By plotting receiver operating characteristic curves, we identified clinical scores that could predict the risk of ICU admission. RESULTS: Out of the 100 patients with Omicron infection, 12 patients were transferred to the ICU due to disease aggravation, with an average of 9.08 days from hospitalization to ICU transfer. Patients transferred to the ICU more commonly experienced shortness of breath, orthopnea, and gastrointestinal bleeding. The peak liver function and changes from baseline in the ICU group were significantly higher, with p values <.05. We found that the baseline platelet-albumin-bilirubin score (PALBI) and neutrophil-to-lymphocyte ratio (NLR) were good predictors of ICU admission risk, with area under curve values of 0.713 and 0.770, respectively. These scores were comparable to the classic Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (p > .05). CONCLUSION: Patients with ESKD and Omicron infection who are transferred to the ICU are more likely to have abnormal liver function. The baseline PALBI and NLR scores can better predict the risk of clinical deterioration and early transfer to the ICU for treatment.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

Brazilian Dialysis Survey 2020.

INTRODUCTION: National data on chronic dialysis treatment are essential to support the development of health policies aimed at improving the treatment for thousands of people. OBJECTIVE: To report epidemiological data from the 2020 Brazilian Dialysis Survey, sponsored by the Brazilian Society of Nephrology. METHODS: A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire for the year, covering clinical and epidemiological aspects of patients in a chronic dialysis program, data on dialysis therapy, characteristics of dialysis units and the impact of the COVID-19 pandemic. RESULTS: 235 (28%) of the centers responded to the questionnaire. In July 2020, the estimated total number of patients on dialysis was 144,779. The estimated prevalence and incidence rates of patients per million population (pmp) were 684 and 209, respectively. Of the prevalent patients, 92.6% were on hemodialysis (HD) and 7.4% were on peritoneal dialysis (PD); 23% were on the transplant waiting list. A central venous catheter was used by a quarter of patients on HD. The incidence rate of confirmed COVID-19 between February and July 2020 was 684/10,000 dialysis patients, and the lethality rate was 25.7%. The estimated overall mortality and COVID-19 crude annual mortality rates were 24.5 and 4.2%, respectively. CONCLUSION: The absolute number of patients on chronic dialysis and prevalence rate continued to increase. The low use of PD as dialysis therapy was maintained and the use of long-term catheters for HD increased. The COVID-19 pandemic contributed to the increase in the overall mortality rate.

Home Hemodialysis: Core Curriculum 2021.

In the early days of dialysis, because of a lack of existing in-center infrastructure, home hemodialysis (HHD) was frequently used to expand dialysis programs. Recently, HHD has been thrust into the spotlight of kidney care programs once again. Patients and policymakers are demanding more choices for the management of kidney failure while controlling for cost. Perhaps it is not surprising that the kidney community's interest in HHD has been revived, especially during the COVID-19 pandemic. To meet this increased interest and demand, nephrologists and dialysis providers must embrace new technologies and improve their understanding of HHD systems. This installment of AJKD's Core Curriculum in Nephrology seeks to inform the reader about factors that can improve success in the training and retention of HHD patients. Benefits, pitfalls, and challenges of HHD are outlined. The features of novel and commonly used HHD equipment are also summarized. Examples of prescriptions and prescription adjustments to meet the needs of patients will also be reviewed. Finally, considerations related to medical management of HHD patients and their dialysis access at home are also included. HHD is an important tool for the management and rehabilitation of patients with kidney failure, which allows for patient-centered care and increased patient choice.

Potent SARS-CoV2-specific T-cell response in asymptomatic hemodialysis patients with hidden COVID-19 infection history.

BACKGROUND: COVID-19-related immune responses in patients with end-stage renal disease (ESRD) are characterized in detail by the humoral response, but their cellular immunity has not been clarified. Here, we evaluated virus-specific T cells in parallel with serology-related tests. METHODS: In this study, 104 ESRD patients at the hemodialysis ward of Imam Reza hospital at Tabriz (Iran) were enrolled. After blood sampling, SARS-CoV2-specific humoral and cellular immune responses were evaluated by SARS-CoV2-specific IgM/IgG ELISA and peptide/MHCI-Tetramers flow cytometry, respectively. RESULTS: Our results showed that 14 (13.5%) and 45 (43.3%) patients had specific SARS-CoV2 IgM and IgG in their sera, respectively. Immunophenotyping for SARS-CoV2-specific CD8+ T lymphocytes revealed that 68 (65.4%) patients had these types of cells. Among SARS-CoV2-specific CD8+ T lymphocytes positive subjects, 13 and 43 individuals had positive results for specific SARS-CoV2 IgM and IgG existence, respectively. Also, there was a relationship between specific SARS-CoV2 IgM (p = 0.031) and IgG (p < 0.0001) existence and having SARS-CoV2-specific TCD8+ lymphocytes in the studied population. CONCLUSION: Despite not having clinical symptoms, a high rate of SARS-CoV2-specific T-cell response in asymptomatic ESRD patients may reveal a high burden of asymptomatic COVID-19 infection in these patients.

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report.

PURPOSE: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are considered particularly susceptible to infection with SARS-CoV2 on the basis of the immunodeficiency associated with advanced age, comorbidity burden, medication use, and need for frequent visits to dialysis clinics. In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used as an adjunct to influenza vaccine. Early in the COVID-19 pandemic we speculated that administration of Ta1 to HD patients would result in reduced rate and severity of COVID-19 infection. We also hypothesized that HD patients treated with Ta1 who did become infected with COVID-19 would have a milder course of infection in terms of hospitalization rates, requirement for and length of ICU stays, requirement for mechanical ventilation, and survival. Further, we proposed that patients who avoided COVID-19 infection during the study would have decreased non-COVID-19 infections and hospitalizations compared to controls. PROCEDURES: The study launched in January 2021 and, as of July 1, 2022, 254 ESRD/ HD patients from five dialysis centers in Kansas City, MO have been screened. Of these, 194 patients have been randomized 1:1 to either Group A (1.6 mg Ta1 given subcutaneously twice weekly for 8 weeks), or Group B (control group not receiving Ta1). After the 8-week treatment period, subjects were followed for an additional 4 months and monitored for safety and efficacy. A data safely monitoring board reviewed all reported adverse effects and commented on study progress. RESULTS: To date, only 3 deaths have occurred in subjects treated with Ta1 (Group A), compared to 7 in the control (Group B). There have been 12 COVID-19 related serious adverse effects (SAEs; 5 in Group A, and 7 in Group B). The majority of patients have received a COVID-19 vaccine (91 patients in group A, and 76 patients in Group B) at various times throughout the study. Nearing completion of the study, blood samples have been collected and antibody responses to COVID-19 will be analyzed along with safety and efficacy endpoints when all subjects have completed the study.

Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis.

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.

One-year all-cause mortality in hospitalized patients with COVID-19 and end-stage renal disease undergoing hemodialysis.

INTRODUCTION: Patients with end-stage renal disease (ESRD) on dialysis and COVID-19 infection have an increased risk of in-hospital mortality, but whether these patients have a higher long-term mortality risk is unknown. MATERIALS AND METHODS: Retrospective chart review of 958 patients admitted with COVID-19 infection or those with ESRD admitted for any other reason between February 2020 and August 2020. We collected data on demographics, comorbidities, laboratory tests, and mortality. The primary outcome was all-cause 1-year mortality. The secondary outcome was in-hospital mortality. We used primarily logistic regression models to assess the mortality risk. RESULTS: In total, 651 patients without ESRD with COVID-19 (COVID+ESRD-), 259 with ESRD without COVID-19 (ESRD+COVID-), and 48 with ESRD with COVID-19 (COVID+ESRD+) were hospitalized between February 2020 and August 2020. Patients were followed after discharge until September 2021. The all-cause 1-year mortality rates were 24% in patients with COVID+ESRD-, 22% in ESRD+COVID- patients, and 40% in those with COVID+ESRD+ (p < 0.05). Compared to the COVID+ESRD- group, the unadjusted and adjusted odds ratio (OR) for all-cause 1-year mortality in the COVID+ESRD+ group was 2.13 (95% confidence interval (CI), 1.16 - 3.91) and 2.15 (95% CI,1.12 - 4.14), respectively. The unadjusted and adjusted OR for all-cause in-hospital mortality in the COVID+ESRD+ group was 1.79 (95% CI, 0.92 - 3.49); and 1.79 (95% CI, 0.88 - 3.65), respectively. We found no statistically significant difference between the COVID+ESRD- and ESRD+COVID- groups for both in-hospital and 1-year mortality (p > 0.05). CONCLUSION: Patients with COVID+ESRD+ have significantly higher odds for all-cause 1-year mortality compared to COVID+ESRD- patients. Future studies should investigate the mechanisms of long-term mortality risk in ESRD patients with COVID-19 infection.

Effects of SARS-CoV-2 vaccination on the severity of COVID-19 infection in patients on chronic dialysis.

BACKGROUND: COVID-19 is associated with increased morbidity and mortality in patients with end-stage kidney disease on dialysis. Efficacy of SARS-CoV-2 vaccination to prevent severe COVID-19 disease in end-stage kidney disease patients remains limited. We compared the incidence of COVID-19-related hospitalization and death in dialysis patients based on SARS-CoV-2 vaccine status. METHODS: Retrospective study of adults on chronic dialysis within Mayo Clinic Dialysis System in the Midwest (USA) between April 1st, 2020 and October 31st, 2022, who had a laboratory test positive for SARS-CoV-2 by PCR. Incidence of both COVID-19-related hospitalization and death were compared between vaccinated and unvaccinated patients. RESULTS: SARS-CoV-2 infection was identified in 309 patients, including 183 vaccinated and 126 unvaccinated. The incidence of death (11.1% vs 3.8%, p = 0.02) and hospitalization (55.6% vs 23.5%, p < 0.001) was significantly higher in unvaccinated compared to vaccinated patients. Age at infection, sex, Charlson comorbidity index, dialysis modality, and hospital stays did not differ between the two groups. The incidence of hospitalization was significantly higher in partially vaccinated (63.6% vs 20.9%, p = 0.004) and unboosted (32% vs 16.4%, p = 0.04) patients compared to fully vaccinated and boosted, respectively. Among the 21 patients who died in the whole cohort, 47.6% (n = 10) died during the pre-vaccine period. The composite risk of death or hospitalization was lower among vaccinated patients after adjusting for age, sex and Charlson comorbidity index (OR 0.24, 95% CI 0.15-0.40). CONCLUSIONS: This study supports the use of SARS-CoV-2 vaccination to improve COVID-19 outcomes in patients on chronic dialysis.

Prevalence and predictors of outcomes among ESRD patients with COVID-19.

BACKGROUND: End-stage renal disease patients on hemodialysis (ESRD) patients are at high risk for contracting COVID-19. In this propensity matched cohort study, we examined the prevalence of COVID-19 in emergency room (ER) patients and examined whether clinical outcomes varied by ESRD status. METHODS: Patients who visited George Washington University Hospital ER from April 2020 to April 2021 were reviewed for COVID-19 and ESRD status. Among COVID-positive ER patients, the propensity for ESRD was calculated using a logistic regression model to create a propensity-matched sample of ESRD vs non-ESRD COVID-19 patients. A multivariable model examined whether ESRD was an independent predictor of death and other outcomes in COVID-19 patients. RESULTS: Among the 27,106 ER patients, 2689 of whom were COVID-positive (9.9%). The odds of testing positive for COVID-19 were 0.97 ([95% CI: 0.78-1.20], p = 0.76) in ESRD vs non-ESRD patients after adjusting for age, sex, and race. There were 2414 COVID-positive individuals with non-missing data, of which 98 were ESRD patients. In this COVID-positive sample, ESRD patients experienced a higher incidence of stroke, sepsis, and pneumonia than non-ESRD individuals. Significant independent predictors of death included age, race, sex, insurance status, and diabetes mellitus. Those with no insurance had odds of death that was 212% higher than those with private insurance (3.124 [1.695-5.759], p < 0.001). ESRD status was not an independent predictor of death (1.215 [0.623-2.370], p = 0.57). After propensity-matching in the COVID-positive patients, there were 95 ESRD patients matched with 283 non-ESRD individuals. In this sample, insurance status continued to be an independent predictor of mortality, while ESRD status was not. ESRD patients were more likely to have lactic acidosis (36% vs 15%) and length of hospital stay ≥ 7 days (48% vs 31%), but no increase in odds for any studied adverse outcomes. CONCLUSIONS: In ER patients, ESRD status was not associated with higher odds for testing positive for COVID-19. Among ER patients who were COVID positive, ESRD was not associated with mortality. However, insurance status had a strong and independent association with death among ER patients with COVID-19.

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19.

INTRODUCTION: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. METHODS: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, ß2 microglobulin and albumin levels pre/post-dialysis and on 1st-2nd week. We compared levels among both techniques and control group (HD without COVID-19). RESULTS: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and ß2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. DISCUSSION: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. CONCLUSION: HDx appears to provide better clearance for TNFα and ß2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Outcomes of vaccinations against respiratory diseases in patients with end-stage renal disease undergoing hemodialysis: A systematic review and meta-analysis.

Due to the nature of the disease, end-stage renal disease (ESRD) patients suffer from dysfunction of the adaptive immune system, which leads to a poorer response to vaccination. Accordingly, it is crucial to evaluate the efficacy and safety of management strategies, including vaccinations, which could potentially reduce the risk of respiratory diseases, such as pneumonia, influenza, or COVID-19, and its associated outcomes. We searched PubMed, CENTRAL, ScienceDirect, Scopus, ProQuest, and Google Scholar databases using designated MeSH keywords. The risk of bias was assessed using ROBINS-I. The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Relative risk (RR) and 95% confidence interval (CI) were calculated. Heterogeneity was investigated using forest plots and I2 statistics. This systematic review included a total of 48 studies, with 13 studies of influenza (H1N1 and H3N2) vaccination and 35 studies of COVID-19 vaccination. H1N1 vaccination in ESRD patients undergoing hemodialysis induced lower seroconversion rates (RR 0.62, 95% CI: 0.56-0.68, p <0.00001) and lower seroprotection rates (RR 0.76, 95% CI: 0.70-0.83, p <0.00001) compared to controls. H3N2 vaccination in ESRD patients undergoing hemodialysis yielded lower seroconversion rates (RR 0.76, 95% CI: 0.68-0.85, p <0.00001) and lower seroprotection rates (RR 0.84, 95% CI: 0.77-0.90, p <0.00001) compared to controls. Twenty-nine studies demonstrate significantly lower antibody levels in ESRD patients undergoing hemodialysis compared to the controls following COVID-19 vaccination. This review presents evidence of lower seroconversion and seroprotection rates after vaccination against viral respiratory diseases in patients with ESRD undergoing hemodialysis. Since hemodialysis patients are more susceptible to infection and severe disease progression, a weakened yet substantial serological response can be considered adequate to recommend vaccination against respiratory diseases in this population. Vaccination dose, schedule, or strategy adjustments should be considered in stable ESRD patients on maintenance hemodialysis. Trial registration: Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255983, identifier: CRD42021255983.

Hemodialysis-Associated Immune Dysregulation in SARS-CoV-2-Infected End-Stage Renal Disease Patients.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1ß and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.