Lessons from SENCOVAC: A prospective study evaluating the response to SARS-CoV-2 vaccination in the CKD spectrum Lecciones aprendidas del SENCOVAC: estudio prospectivo que evalúa la respuesta a la vacunación frente a SARS-CoV-2 en los pacientes con enfermedad renal crónica

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.

Lessons from SENCOVAC: A prospective study evaluating the response to SARS-CoV-2 vaccination in the CKD spectrum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.

Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination.

Continuous evaluation of the coronavirus disease 2019 (COVID-19) vaccine effectiveness in hemodialysis (HD) patients is critical in this immunocompromised patient group with higher mortality rates due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The response towards vaccination in HD patients has been studied weeks after their first and second SARS-CoV-2 vaccination dose administration, but no further studies have been developed in a long-term manner, especially including both the humoral and cellular immune response. Longitudinal studies that monitor the immune response to COVID-19 vaccination in individuals undergoing HD are therefore necessary to prioritize vaccination strategies and minimize the pathogenic effects of SARS-CoV-2 in this high-risk group of patients. We followed up HD patients and healthy volunteers (HV) and monitored their humoral and cellular immune response three months after the second (V2+3M) and after the third vaccination dose (V3+3M), taking into consideration previous COVID-19 infections. Our cellular immunity results show that, while HD patients and HV individuals secrete comparable levels of IFN-γ and IL-2 in ex vivo stimulated whole blood at V2+3M in both naïve and COVID-19-recovered individuals, HD patients secrete higher levels of IFN-γ and IL-2 than HV at V3+3M. This is mainly due to a decay in the cellular immune response in HV individuals after the third dose. In contrast, our humoral immunity results show similar IgG binding antibody units (BAU) between HD patients and HV individuals at V3+3M, independently of their previous infection status. Overall, our results indicate that HD patients maintain strong cellular and humoral immune responses after repeated 1273-mRNA SARS-CoV-2 vaccinations over time. The data also highlights significant differences between cellular and humoral immunity after SARS-CoV-2 vaccination, which emphasizes the importance of monitoring both arms of the immune response in the immunocompromised population.

Impact of public restrictive measures on hypertension during the COVID-19 pandemic: existing evidence and long-term implications.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in December 2019 and emerged into an ongoing global pandemic. Both the pandemic itself and the associated public restrictive measures of social mobility established with different intensity over different periods in various countries have significantly affected the everyday activities and lifestyles of people all over the world. The impact of lockdown and quarantine measures on hypertension incidence and blood pressure (BP) control is an important topic that requires further investigation. The aim of this review is: a) to present the current evidence regarding the actual effects of public restrictive measures on BP levels and control, originating primarily from studies investigating the impact of public restrictive measures on BP control with the use of various BP phenotypes; b) to summarize the possible pandemic-related effects of factors known to affect BP levels, including both traditional (e.g. dietary habits including alcohol and sodium intake, body weight, smoking and physical activity) and non-traditional (e.g. sleep patterns, air pollution, environmental noise, delayed diagnosis and medication adherence) ones.

Acute and chronic kidney disease and risk of hospital mortality during COVID-19 pandemic waves in the pre-vaccination era.

Background: Chronic kidney disease (CKD) is a risk factor for death from coronavirus disease 2019 (COVID-19), and COVID-19 may cause acute kidney injury (AKI) which also influences outcomes. There is little information on the independent contribution of CKD and AKI to the risk of death in COVID-19 on different waves, as CKD is a key risk factor for AKI. Methods: We have studied the epidemiology of CKD and AKI in 2878 patients hospitalized for COVID-19 and their independent association with in-hospital mortality in the two largest pre-vaccination COVID-19 waves in Madrid, Spain. Hospitalized COVID-19 patients were grouped into four mutually exclusive categories: previous-CKD, community-acquired AKI (CA-AKI), hospital-acquired AKI (HA-AKI) and normal renal function throughout hospitalization. Results: Pre-existent or acquired kidney involvement was observed in 35.5% and 36.8% of COVID-19 patients in the 1st and 3rd waves, respectively. Overall, 13.9% of patients with normal kidney function on arrival developed HA-AKI. In the 3rd wave, CA-AKI was more common than in the 1st wave. Overall, 9%-20% of CKD cases and 22%-40% of AKI cases remained undiagnosed in the discharge report. CKD, CA-AKI and HA-AKI were independently associated with risk of death in multivariate analysis, with HA-AKI, which was usually mild, being the most relevant independent risk factor for in-hospital mortality. A model including kidney involvement category, age, Charlson index, admission lactate dehydrogenase and lymphocytes predicted death with a receiver operating characteristic area under the curve of 0.898. Conclusion: In conclusion, CKD and AKI were common in pre-vaccination waves among hospitalized COVID-19 patients and were independent risk factors for death, even when AKI was mild to moderate, and despite improvements in treatment.

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.

Preparing European Nephrology for the next pandemic: lessons from the ERACODA collaboration.

Owing to the vulnerability of patients with chronic kidney disease to infectious diseases, the coronavirus disease 2019 (COVID-19) pandemic has been particularly devastating for the nephrology community. Unfortunately, the possibility of future COVID-19 waves or outbreaks of other infectious diseases with pandemic potential cannot be ruled out. The nephrology community made tremendous efforts to contain the consequences of the COVID-19 pandemic. Despite this, the COVID-19 pandemic has highlighted several shortcomings in our response to the pandemic and has taught us important lessons that can be utilized to improve our preparedness for any future health crises of similar nature. In this article we draw lessons from the European Renal Association COVID-19 Database (ERACODA) project, a pan-European collaboration initiated in March 2020 to understand the prognosis of COVID-19 in patients on kidney function replacement therapy. We discuss challenges faced in generating timely and robust evidence for informed management of patients with kidney disease and give recommendations for our preparedness for the next pandemic in Europe. Limited collaboration, the absence of common data architecture, and the sub-optimal quality of available data posed challenges in our response to COVID-19. Aligning different research initiatives, strengthening electronic health records, and involving experts in study design and data analysis will be important in our response to the next pandemic. The European Renal Association may take a leading role in aligning research initiatives via its engagement with other scientific societies, national registries, administrators, and researchers.

RICORS2040: the need for collaborative research in chronic kidney disease.

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true.

Humoral response after the fourth dose of the SARS-CoV-2 vaccine in the CKD spectrum: a prespecified analysis of the SENCOVAC study.

BACKGROUND: There is scarce evidence on fourth doses of SARS-CoV-2 vaccines in chronic kidney disease (CKD) patients. We have evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analyzed factors associated to persistent negative humoral response and to higher anti-Spike antibody titers as well as the efficacy of vaccination on COVID-19 severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titers in HD (P = 0.001) and ND-CKD (P = 0.014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titers at 12 months were independently associated to repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titers and not being a KT. Breakthrough COVID-19 was registered in 137 (6%) patients, of whom 5% required admission. Admitted patients had prior titers below 620 UI/ml and median values were lower (P = 0.020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titers or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titers or KT recipients) derived the least benefit in terms of antibody titers. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titers.

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study.

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.

Construct Validity and Test-Retest Reliability of a Free Mobile Application to Evaluate Aerobic Capacity and Endurance in Post-COVID-19 Syndrome Patients-A Pilot Study.

Introduction: Disability associated with the symptoms of post-COVID-19 syndrome is one of its main features and can have a considerable impact on care and rehabilitation units. This, linked to a decreased aerobic capacity and endurance in post-COVID-19 syndrome patients, increases interest in studying the potential of mobile applications to assess performance capacity. The purpose of this research was to study how a free mobile application assesses aerobic capacity and endurance and its relationship with aerobic capacity, test-retest reliability, and endurance evaluated by a conventional test, along with fatigue and health-related quality of life. Methods: An observational study was conducted. RUNZI®, a free mobile application, was used by mounting a Samsung Galaxy S8 smartphone using a strap on the right forearm while all participants simultaneously performed a 6-Minute Walking Test (6MWT). Construct validity between the 6MWT and the total distance performed evaluated by RUNZI® was explored. Additionally, evaluation scales to assess fatigue (MFIS) and health-related quality of life (SF-36) were used to analyze the construct validity of RUNZI®. For test−retest reliability of the app, the same instructions about the 6MWT and procedure with the app were given to all participants at two different time periods. Results: A total of 16 post-COVID-19 syndrome patients (15 females and 1 male) completed the procedure. Distance measured with the RUNZI® showed an excellent correlation with the 6MWT assessed conventionally (p < 0.0001; r = 0.851). No statistical correlations were found between the distance assessed by the RUNZI® app with MFIS and the SF-36. Test−retest reliability was found to be close to statistical significance (p = 0.058) for distance (m) measured by RUNZI® with an ICC of 0.482. Conclusions: Instrumental 6MWT assessed by the RUNZI® app for the Android® operating system showed an excellent correlation with conventional 6MWT, indicating its construct validity in post-COVID-19 syndrome patients. Further, values for the test−retest reliability for the free mobile application were close to statistical significance with a reliability considered poor in an indoor setting.

A GBD 2019 study of health and Sustainable Development Goal gains and forecasts to 2030 in Spain.

This study aimed to report mortality, risk factors, and burden of diseases in Spain. The Global Burden of Disease, Injuries, and Risk Factors 2019 estimates the burden due to 369 diseases, injuries, and impairments and 87 risk factors and risk factor combinations. Here, we detail the updated Spain 1990-2019 burden of disease estimates and project certain metrics up to 2030. In 2019, leading causes of death were ischaemic heart disease, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and lung cancer. Main causes of disability adjusted life years (DALYs) were ischaemic heart disease, diabetes, lung cancer, low back pain, and stroke. Leading DALYs risk factors included smoking, high body mass index, and high fasting plasma glucose. Spain scored 74/100 among all health-related Sustainable Development Goals (SDGs) indicators, ranking 20 of 195 countries and territories. We forecasted that by 2030, Spain would outpace Japan, the United States, and the European Union. Behavioural risk factors, such as smoking and poor diet, and environmental factors added a significant burden to the Spanish population's health in 2019. Monitoring these trends, particularly in light of COVID-19, is essential to prioritise interventions that will reduce the future burden of disease to meet population health and SDG commitments.

The last pre-pandemic European Renal Association Registry report: age at start of kidney replacement therapy in Europe.

The European Renal Association (ERA) Registry Annual Report 2019 will be its last pre-pandemic report. From 2020 on, registry data will incorporate any potential impact of coronavirus disease 2019 (COVID-19) on kidney replacement therapy (KRT) practices in Europe. The 2019 report focussed on age comparisons and found substantial differences in the distribution of primary renal disease, treatment modality, kidney donor type and the survival probabilities for different age categories. The report presents data that support a correlation (R 2 = 0.43, P < 0.00001) between the incidence of KRT per million population (pmp) and the median age at the start of KRT in the different regions and countries, suggesting that initiating KRT at an older median age may be a determinant of KRT incidence. The causes of the lower age at KRT in some countries should be explored. These may include, but are not limited to, KRT not being offered to the elderly or the elderly refusing KRT. In this regard, there was a correlation between the median age at the start of KRT and per capita gross domestic product (GDP) (R 2 = 0.26, P < 0.0046), suggesting that the availability of resources may be a factor that limits the offer of KRT to the elderly. The UK may represent a case to study these issues. Both age at initiation of KRT and KRT incidence are below the European median and lower than that expected for GDP. Furthermore, there are differences between the various countries within the UK, as well as documented racial differences, the latter being a piece of information missing for most European countries.

Long-Term Dynamic Humoral Response to SARS-CoV-2 mRNA Vaccines in Patients on Peritoneal Dialysis.

INTRODUCTION: Patients on peritoneal dialysis (PD) present an impaired humoral response against SARS-CoV-2, at least after the initial vaccination and booster dose. Until now, the effect of a fourth dose has not been established. The aim of the present study is to evaluate the long-term dynamics of the humoral response of PD patients to multiple doses of SARS-CoV-2 vaccines, focusing on the effect of the fourth dose. METHODS: This is an analysis of the prospective and multicentric SENCOVAC study. We included patients on PD without additional immunosuppression that had received at least 3 SARS-CoV-2 mRNA vaccine doses. We evaluated anti-spike antibody titers after the initial vaccination, third and fourth doses, using prespecified fixed assessments (i.e., baseline, 28 days, 3, 6, and 12 months after completing the initial vaccine schedule). Breakthrough infections were also collected. RESULTS: We included 164 patients on PD (69% males, 62 ± 13 years old). In patients who had received only two doses, the rates of positive humoral response progressively decreased from 96% at 28 days to 80% at 6 months, as did with anti-spike antibody titers. At 6 months, 102 (62%) patients had received the third vaccine dose. Patients with the third dose had higher rates of positive humoral response (p = 0.01) and higher anti-spike antibody titers (p < 0.001) at 6 months than those with only 2 doses. At 12 months, the whole cohort had received 3 vaccine doses, and 44 (27%) patients had an additional fourth dose. The fourth dose was not associated to higher rates of positive humoral response (100 vs. 97%, p = 0.466) or to statistically significant differences in anti-spike antibody titers as compared to three doses (p = 0.371) at 12 months. Prior antibody titers were the only predictor for subsequent higher anti-spike antibody titer (B 0.53 [95%CI 0.27-0.78], p < 0.001). The 2 (1.2%) patients that developed COVID-19 during follow-up had mild disease. CONCLUSIONS: PD presents an acceptable humoral response with three doses of SARS-CoV-2 vaccines that improve the progressive loss of anti-spike antibody titers following two vaccine doses.

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study.

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.

Anti-Spike antibodies three months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Introduction Patients on hemodialysis are at high-risk for complications derived from coronavirus disease-19 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity three months after the booster dose. Methods This is a multicentric and prospective study assessing IgG anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results A total of 711 patients (67% male, 67 [20-89] years) were included. Of which, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, p = 0.001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, p = 0.693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated to mRNA-1273 booster (p = 0.001), lower time from booster (p = 0.043) and past breakthrough SARS-CoV-2 infection (p<0.001). Conclusions In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated to mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection. Graphical Graphical

Humoral Response to Third Dose of Sars-Cov-2 Vaccines in the CKD Spectrum: The Sencovac Study

BACKGROUND AND AIMS There is incomplete information on the impact of a third dose of the SARS-CoV-2 vaccine in advance chronic kidney disease (CKD). The aim of the present analysis was to evaluate the kinetics of humoral response in the CKD spectrum (KT, HD, PD and ND-CKD) 6 months after completing the initial vaccine schedule. Some patients of each group received a third dose before 6 months, providing a pragmatic insight into real-world responses to different vaccine schedules in patients with advanced CKD not on dialysis, on dialysis or in KT recipients. METHOD The SENCOVAC study describes the humoral response and safety of different SARS-CoV-2 vaccines in a real-world setting in 3687 CKD patients: 787 kidney transplant (KT), 319 peritoneal dialysis (PD), 2297 haemodialysis (HD) and 284 non-dialysis-CKD (ND-CKD) patients. Anti-Spike antibodies were assessed in an efficacy analysis at 28 days (n = 1755), 3 months (n = 1386), and 6 months (n = 1018, of whom 628 had received a third vaccine dose). Adverse events (AEs) were registered during follow-up, including SARS-CoV-2 infections in the safety analysis. RESULTS Among the patients included in the efficacy analysis, KT recipients presented lower anti-Spike antibody titers than other CKD cohorts at 28 days and 3 months (P < .001 for all). A total of 943 patients [249 (26%) KT, 108 (11%) PD, 511 (54%) HD and 75 (8%) ND-CKD] had negative baseline anti-Spike antibodies. Again, at 28 days or 3 months, KT recipients developed lower anti-Spike antibody titers than PD (P < .001), HD (P < .001) and ND-CKD (P< .001) patients. At 6 months, patients that had received a third vaccine dose had higher anti-Spike antibody titers than those without the third dose [1837 (507–9726) UI/mL versus 80 (19–409) ml/UI;P < .001] and this was evident in all CKD cohorts. Anti-Spike titers after the third dose were higher in patients boosted with mRNA-1273 than with BNT162b2 [1710 (322–9615) versus 472 (34–2094);P < .001). At 6 months, in patients that had received a third dose, a positive humoral response (anti-Spike antibodies > 36 UI/mL) was achieved in 584 (93%): 94 (80%) of 118 KT recipients, 20 (100%) of 20 patients on PD, 436 (96%) of 455 patients on HD and 34 (97%) of 35 patients with ND-CKD (Fig. 1). Among patients without humoral response 3 months after completing the initial vaccination schedule, 72 (69%) seroconverted after the third dose (62% KT, 76% HD, 100% ND-CKD, all PD patients had a positive humoral response at 3 months). Independent predictors of a positive humoral response at 6 months were not-KT (HR for KT 0.26, P = .011), third dose (HR 22.9, P < .001), initial mRNA-1273 (HT 1.78, P = .017) and humoral response at 3 months (HR 26.2, P < .001). Breakthrough SARS-CoV-2 infections occurred in 1.1% of patients, and mortality was 14.6%, none after the third dose. CONCLUSION In the CKD spectrum, anti-Spike antibody titers continued to decrease from 3 to 6 months after complete vaccination, and KT recipients presented higher rates of negative humoral response at 6 months. A third dose of mRNA vaccine increased anti-Spike antibody titers but was still insufficient to spur a humoral immune response in at least 38% of KT recipients and 24% of patients on HD that lacked anti-SARS-CoV-2 antibodies 3 months post-initial vaccination. New strategies are urgently needed to protect CKD patients that remain negative for anti-SARS-CoV-2 antibodies, given the high mortality of breakthrough SARS-CoV-2 infections.FIGURE 1: Presence of anti-Spike antibodies during follow-up in the different CKD cohorts. Data expressed as % of patients with presence of anti-Spike antibodies (i.e. titer > 36 IU/mL). GRAPHICAL Graphical

Impact of different COVID-19 waves on kidney replacement therapy epidemiology and mortality: REMER 2020.

BACKGROUND: Kidney replacement therapy (KRT) confers the highest risk of death from coronavirus disease 2019 (COVID-19). However, most data refer to the early pandemic waves. Whole-year analysis compared with prior secular trends are scarce. METHODS: We present the 2020 REMER Madrid KRT registry, corresponding to the Spanish Region hardest hit by COVID-19. RESULTS: In 2020, KRT incidence decreased 12% versus 2019, while KRT prevalence decreased by 1.75% for the first time since records began and the number of kidney transplants (KTs) decreased by 16%. Mortality on KRT was 10.2% (34% higher than the mean for 2008-2019). The 2019-2020 increase in mortality was larger for KTs (+68%) than for haemodialysis (+24%) or peritoneal dialysis (+38%). The most common cause of death was infection [n = 419 (48% of deaths)], followed by cardiovascular [n = 200 (23%)]. Deaths from infection increased by 167% year over year and accounted for 95% of excess deaths in 2020 over 2019. COVID-19 was the most common cause of death (68% of infection deaths, 33% of total deaths). The bulk of COVID-19 deaths [209/285 (73%)] occurred during the first COVID-19 wave, which roughly accounted for the increased mortality in 2020. Being a KT recipient was an independent risk factor for COVID-19 death. CONCLUSIONS: COVID-19 negatively impacted the incidence and prevalence of KRT, but the increase in KRT deaths was localized to the first wave of the pandemic. The increased annual mortality argues against COVID-19 accelerating the death of patients with short life expectancy and the temporal pattern of COVID-19 mortality suggests that appropriate healthcare may improve outcomes.