Humoral immunity to SARS-CoV-2 in kidney transplant recipients and dialysis patients: IgA and IgG patterns unraveled after SARS-CoV-2 infection and vaccination.

BACKGROUND: Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. METHODS: Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. RESULTS: Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. CONCLUSION: Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.

Prevention of tunneled cuffed catheter dysfunction with prophylactic use of a taurolidine urokinase lock: A randomized double-blind trial.

BACKGROUND: The efficacy and cost-effectiveness of prophylactic thrombolytic locks in hemodialysis patients at high-risk of thrombotic dialysis catheter dysfunction is uncertain. We investigated this question in a double-blinded randomized controlled study. METHODS: Prevalent hemodialysis patients from 8 Belgian hemodialysis units, with ≥2 separate episodes of thrombotic dysfunction of their tunneled cuffed catheter during the 6 months before inclusion, were randomized to either: taurolidine heparin locks thrice weekly (control arm) or the same locks twice a week combined with taurolidine urokinase locks once a week before the longest interval without HD (TaurolockU arm). The primary efficacy outcome was the incidence rate of catheter thrombotic dysfunction requiring thrombolytic locks to restore function. RESULTS: 68 hemodialysis patients (32 controls, 36 urokinase) were followed during 9875 catheter days between May 2015 and June 2017. Incidence rate of thrombotic catheter dysfunction was 4.8 in TaurolockU vs 12.1/1000 catheter days in control group (rate ratio 0.39; 95%CI 0.23-0.64). 15/36 (42%) catheters in the treatment group required at least one therapeutic urokinase lock vs 23/32 (72%) in the control group (P = 0.012). The two groups did not differ significantly in catheter-related bloodstream infection and combined cost of prophylactic and therapeutic catheter locks. The TaurolockU group had a numerically higher number of episodes of refractory thrombosis. CONCLUSIONS: Prophylactic use of urokinase locks is highly effective in reducing the number of thrombotic catheter dysfunctions in catheters with a history of recurring dysfunction. Prophylactic use of urokinase locks did not reduce the overall costs associated with catheter locks and was associated with a numerically higher number of episodes of refractory thrombosis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

Urokinase-containing locking solution in the prevention of dialysis catheter dysfunction: a double blind randomized controlled trial.

INTRODUCTION: The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction. METHODS: Patients with a history of at least two separate TCC thrombotic dysfunctions treated with urokinase lock during the 6 months preceding inclusion are recruited in eight Belgian dialysis units. Patients are randomized in two groups: the control group receiving Taurolock™-HEP500 (heparin 500 IU/mL, taurolidine, citrate 4%) after each hemodialysis session and the treatment group receiving Taurolock-U 25,000 (urokinase 25,000, taurolidine, citrate 4%) once a week and the standard Taurolock-HEP500 at the end of the two others sessions. The primary outcome is the incidence rate of TCC thrombotic dysfunction defined by the use of urokinase. The secondary outcomes are the incidence rate of TCC removal and systemic thrombolysis. For the study, both patients and healthcare staff are blinded to treatment allocation. CONCLUSIONS: The present trial is the first to investigate the effect of Taurolock-U 25,000 catheter lock once a week as secondary prevention in hemodialysis patients with the highest risk of TCC-related thrombotic dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

Immunogenicity and safety of an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency who failed to respond or to maintain antibody levels after prior vaccination: results of two open, randomized, comparative trials.

An investigational AS02(v)-adjuvanted hepatitis B (HB-AS02) was compared with a licensed conventional recombinant hepatitis B vaccine (HBVAXPRO™; Sanofi Pasteur MSD, Lyon, France) in pre-dialysis, peritoneal dialysis and hemodialysis patients aged ≥18 years who had failed either to respond to prior vaccination with a conventional hepatitis B vaccine (Study A; n=251) or to maintain protective antibody concentrations after prior hepatitis B vaccination (Study B; n=181). These were open, randomized, comparative trials. Mean (range) age was 65.9 (31-92) and 64.6 (29-92) years in the two studies, respectively. In Study A, two doses of HB-AS02 given one month apart were found to be superior to two doses of the licensed vaccine in terms of seroprotection rate (76.9% versus 37.6%) and anti-HBs geometric mean antibody concentration (GMC; 139.3 versus 6.9mIU/ml), with antibody concentrations ≥100mIU/ml in 61.1% and 15.4% of subjects in the two groups, respectively. In Study B, one month after administration of a single booster dose, seroprotection rates were 89.0% in the HB-AS02 group and 90.8% in the licensed vaccine group, 81.3% and 60.9% of subjects had antibody concentrations ≥100mIU/ml, and anti-HBs GMCs were 1726.8 and 189.5mIU/ml. HB-AS02 was found to be more reactogenic than the licensed vaccine. In summary, the investigational HB-AS02 vaccine induced higher seroprotection rates and anti-HBs GMCs than a licensed conventional hepatitis B vaccine in uremic patients who had failed to respond or to maintain protective antibody titers after prior hepatitis B vaccination.

Rapid, enhanced, and persistent protection of patients with renal insufficiency by AS02(V)-adjuvanted hepatitis B vaccine.

The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02 with that of HB-AS04. In this phase III, open, randomized study, 151 hepatitis B vaccine-naïve pre-dialysis, peritoneal dialysis, and hemodialysis patients aged 15 years and older received three doses of HB-AS02 at 0, 1, and 6 months. Another 149 similar patients received four doses of HB-AS04 at 0, 1, 2, and 6 months, and all were followed up for 12 months. HB-AS02 elicited more rapid and persistent seroprotection than HB-AS04, with rates of 77 and 39%, respectively, 1 month after the second vaccine dose, and 94 and 79%, respectively, at 12 months. Superiority of HB-AS02 over HB-AS04 in anti-hepatitis B geometric mean concentrations was found at all time points. HB-AS02 was more reactogenic than HB-AS04, but adverse events were mainly transient, of mild to moderate intensity with no reportable vaccine-related serious events. We conclude that a three-dose primary course of HB-AS02 induced more rapid, enhanced, and persistent protection in patients with renal insufficiency than the licensed four-dose primary schedule of HB-AS04. This adjuvanted vaccine affords greater protection with reduced need for booster doses in patients at high risk of hepatitis B infection.