Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * krev imunologie MeSH
- příjemce transplantátu * MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 imunologie aplikace a dávkování MeSH
- vakcíny proti COVID-19 imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Acute kidney injury in deceased donors (D-AKI) is one of the common causes of donor kidney discard. The risk factors for D-AKI and its impact on kidney transplantation outcomes are not yet fully understood. METHODS: This single-center, retrospective cohort study included 388 donors referred between June 2021 and December 2022. D-AKI was defined and staged according to kidney disease: Improving global outcomes criteria, and donor clinical variables were analyzed to identify risk factors for D-AKI. Delayed graft function and estimated glomerular filtration rate (eGFR) at 6 mo were evaluated in 369 kidney grafts transplanted from donors with and without D-AKI. RESULTS: AKI was present in 171 deceased donors (44.1%), with 117 (30.2%) classified as AKI stage 1 and 54 (14%) as AKI stages 2 or 3. Donor history of hypertension (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.21-3.10; P = 0.005), history of diabetes (OR 2.2; 95% CI, 1.21-3.98; P = 0.008), and anoxia as the cause of death (OR 2.61; 95% CI, 1.5-4.61; P < 0.001) were independently associated with an increased risk of D-AKI. Multivariable mixed models identified donor age (β -0.49; 95% CI, -0.71 to -0.28; P < 0.001) as the only independent risk factor for lower eGFR at 6 mo. D-AKI was not associated with delayed graft function or lower eGFR at 6 mo. CONCLUSIONS: Hypertension, diabetes, and anoxia as the cause of death were identified as risk factors for AKI in deceased donors. D-AKI should not be used as the sole criterion to assess the risk of poor graft outcomes. A broader range of donor variables should be considered when evaluating graft viability.
- Publikační typ
- časopisecké články MeSH
Pacienti s chronickým onemocněním ledvin představují z hlediska infekčních komplikací jednu z vůbec nejrizikovějších skupin pacientů. Covid‐19 má na tuto populaci celou řadu zásadních dopadů, a je proto nutné k prevenci a léčbě tohoto onemocnění přistupovat v souladu se současným stavem poznání. V následujícím článku budou shrnuta poslední platná doporučení ohledně vakcinace proti onemocnění covid‐19 i jeho léčby se zaměřením na praktické možnosti zlepšení odpovědi na vakcinaci a další metody ochrany této ohrožené populace.
BACKGROUND: Infliximab selectively targets recently activated effector cells and, as an induction agent, might enable the safe elimination of mycophenolate from maintenance immunosuppression in kidney transplantation. METHODS: This is a phase II international multicenter open-label single-arm confidence interval (CI)-based clinical trial of the BIO-DrIM EU consortium aimed at assessing the efficacy and safety of rabbit antithymocyte globulin and infliximab induction in kidney transplantation. Sixty-seven primary kidney transplant recipients at low risk (panel-reactive antibodies <20%, no donor-specific antibodies [DSA]) received rabbit antithymocyte globulin (2 × 1.5 mg/kg, postoperative days 0 and 1) and infliximab (5 mg/kg, postoperative day 2), followed by mycophenolate-free tacrolimus-based immunosuppression for 12 mo. The primary endpoint was efficacy failure, defined as a composite of acute rejection, graft loss, or poor graft function (estimated glomerular filtration rate <40 mL/min) at 12 mo and was based on the endpoint of the comparator study. Additionally, a historical propensity-matched control cohort was established. RESULTS: Primary endpoint occurred in 22 of 67 patients (32.84%), with upper bound of an exact 1-sided 95% CI of 43.47%, which met the predefined criteria (efficacy failure of <40% and upper-bound 95% CI of <50%) and was similar in the historical matched cohort. By 12 mo, 79.1% of patients remained on the study protocol. Lower rates of BK replication (6% versus 22.4%; P = 0.013) but higher rates of de novo DSAs (11.9% versus 1.5%; P = 0.039) were observed in the study cohort. CONCLUSIONS: A similar efficacy of the study immunosuppression regimen to the comparator study and the historical matched cohort was found. However, a higher de novo DSA emergence points to an increased risk of antibody-mediated rejection (NCT04114188).
- MeSH
- antilymfocytární sérum * MeSH
- imunosupresiva škodlivé účinky MeSH
- imunosupresivní léčba MeSH
- infliximab škodlivé účinky MeSH
- inhibitory enzymů MeSH
- lidé MeSH
- přežívání štěpu MeSH
- protilátky MeSH
- rejekce štěpu prevence a kontrola MeSH
- takrolimus * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
BACKGROUND: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. METHODS: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. RESULTS: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. CONCLUSIONS: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).
- Publikační typ
- časopisecké články MeSH
- MeSH
- imunosupresiva škodlivé účinky MeSH
- inhibitory kalcineurinu * škodlivé účinky MeSH
- lidé MeSH
- prognóza MeSH
- takrolimus škodlivé účinky MeSH
- transplantace ledvin škodlivé účinky MeSH
- trombotické mikroangiopatie * etiologie chemicky indukované patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- úvodníky MeSH
Although severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid (SARS-CoV-2 mRNA) vaccines are effective in kidney transplant recipients (KTRs), their immune response to vaccination is blunted by immunosuppression. Other tools enhancing vaccination response are therefore needed. Interestingly, aligning vaccine administration with circadian rhythms (chronovaccination) has been shown to boost immune response. However, its applicability in KTRs, whose circadian rhythms are likely disrupted by immunosuppressants, remains unclear. To assess the impact of vaccination timing on seroconversion in the KTRs population, we analyzed data from 553 virus-naïve KTRs who received 2 doses of messenger ribonucleic acid (mRNA) vaccine. Bayesian logistic regression was employed, adjusting for previously identified predictors of seroconversion, including allograft function, maintenance immunosuppressants, or time since transplantation. SARS-CoV-2 immunoglobulin G (IgG) levels were measured with a median of 47 days after the second dose. The results did not reveal a reliable effect of timing of the first dose but did indicate that earlier timing for the second dose brings a notable benefit-every 1-hour delay in the application was associated with a 16% reduction in the odds of seroconversion (OR 0.84, 95% CI 0.71, 0.998). Similar results were obtained from quantile regression modeling IgG levels. In conclusion, morning vaccination is emerging as a promising and easily implementable strategy to enhance vaccine response in KTRs.
- MeSH
- chronické selhání ledvin chirurgie imunologie MeSH
- cirkadiánní rytmus imunologie MeSH
- COVID-19 * prevence a kontrola imunologie MeSH
- dospělí MeSH
- humorální imunita * MeSH
- imunoglobulin G krev imunologie MeSH
- imunosupresiva aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- příjemce transplantátu MeSH
- protilátky virové * krev imunologie MeSH
- rejekce štěpu imunologie prevence a kontrola MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 * imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
