Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated With Antithymocyte Globulin: A Randomized Clinical Trial.

BACKGROUND: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. METHODS: In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). RESULTS: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. CONCLUSIONS: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. CLINICAL TRIALS REGISTRATION: NCT03123627.

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation.

BACKGROUND: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. METHODS: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI. RESULTS: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL. CONCLUSIONS: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery.

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

BACKGROUND: Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. METHODS: An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. RESULTS: A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8+ CD69+ INF-γ+ T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8+ CD69+ INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CONCLUSIONS: CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation.

A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome.

Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients.

[Randomized clinical trial on the effectiveness of a postal reminder to increase tetanus-diphtheria vaccination coverage in the young adult population]. / Ensayo clínico aleatorizado acerca de la efectividad del recordatorio postal para aumentar la cobertura vacunal contra tétanos-difteria en población adulta joven.

OBJECTIVE: To evaluate the effectiveness of individual postal reminders compared with no action of any kind in increasing the tetanus-diphtheria immunization rate in the population aged between 24 and 30 years old in an area where a general population strategy was simultaneously being conducted through information posters on tetanus vaccination. METHOD: We performed an open, randomized clinical trial with parallel groups among the population aged 24-30 years old in a basic health area with 13,523 inhabitants over a 3-month period in 2005. There were 311 patients in the control group and 311 in the experimental group, after exclusion of individuals correctly vaccinated according to the computerized medical records system. The intervention evaluated was a postal reminder on tetanus vaccination. The response variable was the immunization rate due to the intervention. Other variables studied were sex, age, reason for seeking vaccination, compliance with the vaccination timetable, whether vaccination was rejected, and whether prior vaccination was verified. The statistical analysis consisted of Student's t-test and the chi2 test, with a confidence level of 95% (p < 0.05). RESULTS: Vaccination coverage among the general population at the end of 2005 was 75.6%. After the postal reminder, 22.2% of the control group and 40.5% of the experimental group were correctly vaccinated. CONCLUSIONS: Individual postal reminders sent to the population aged between 24 and 30 years is effective in increasing the immunization rate in this age group. Periodic reminders could help to ensure continuity in vaccination of the adult population.

Ensayo clínico aleatorizado acerca de la efectividad del recordatorio postal para aumentar la cobertura vacunal contra tétanos-difteria en población adulta joven / Randomized clinical trial on the effectiveness of a postal reminder to increase tetanus-diphtheria vaccination coverage in the young adult population

Objetivo. Evaluar la efectividad de los recordatorios postales individualizados frente a ningún tipo de intervención, para incrementar la tasa de inmunización con vacuna contra tétanos-difteria en la población de entre 24 y 30 años de edad, en un área donde simultáneamente se efectúa una estrategia poblacional general mediante carteles informativos acerca de la vacuna antitetánica. Método. Ensayo clínico, aleatorizado, abierto, con grupos paralelos, en una ABS de 13.523 habitantes, realizado en la población de 24-30 años, durante parte de 2005, con una muestra de 311 pacientes en el grupo control y 311 en el grupo intervenido, tras excluir los bien vacunados según el registro informático de la historia clínica. La intervención que se evalúa es el recordatorio postal acerca de la vacunación antitetánica y su repercusión debida a la intervención sobre la tasa de inmunización. También se recogieron datos sobre: sexo, edad, motivo para haber venido a vacunarse, cumplimiento de horario, si se rehusa la vacuna y si se comprueba que ya estaba bien vacunado previamente. Para el análisis estadístico se utilizaron la t de Student y el test de la x2, con un nivel de confianza del 95% (p < 0,05). Resultados. La cobertura vacunal poblacional a finales de 2005 ha sido del 75,6%. Tras el recordatorio postal estaba bien vacunado un 22,2% del grupo control y un 40,5% del grupo intervenido. Conclusiones. El recordatorio postal individualizado a la población de 24 a 30 años de esta área de salud es efectivo para incrementar la tasa de inmunización en este grupo de edad, y la realización periódica puede asegurar una continuidad en la vacunación de la población adulta

Objective. To evaluate the effectiveness of individual postal reminders compared with no action of any kind in increasing the tetanus-diphtheria immunization rate in the population aged between 24 and 30 years old in an area where a general population strategy was simultaneously being conducted through information posters on tetanus vaccination. Method. We performed an open, randomized clinical trial with parallel groups among the population aged 24-30 years old in a basic health area with 13,523 inhabitants over a 3-month period in 2005. There were 311 patients in the control group and 311 in the experimental group, after exclusion of individuals correctly vaccinated according to the computerized medical records system. The intervention evaluated was a postal reminder on tetanus vaccination. The response variable was the immunization rate due to the intervention. Other variables studied were sex, age, reason for seeking vaccination, compliance with the vaccination timetable, whether vaccination was rejected, and whether prior vaccination was verified. The statistical analysis consisted of Student's t-test and the x2 test, with a confidence level of 95% (p < 0.05). Results. Vaccination coverage among the general population at the end of 2005 was 75.6%. After the postal reminder, 22.2% of the control group and 40.5% of the experimental group were correctly vaccinated. Conclusions. Individual postal reminders sent to the population aged between 24 and 30 years is effective in increasing the immunization rate in this age group. Periodic reminders could help to ensure continuity in vaccination of the adult population