SARS-CoV-2 antibody dynamics among kidney transplant recipients 3 months after BNT162b2 vaccination: a prospective cohort study.

Data regarding immunogenicity of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among kidney transplant recipients in the months following vaccination are lacking. We aimed to investigate humoral immune response at 3-4 months post-vaccination among a cohort of kidney transplant recipients, compared with a control group of dialysis patients. Anti-spike antibodies were tested at 1 and 3-4 months after vaccination. Of 259 kidney transplant recipients tested at a median time of 110 days from second vaccine dose, 99 (38%) were seropositive, compared with 83% (101/122) of control patients. Younger age, better renal function and lower immunosuppression levels were associated with seropositivity. A total of 14% (13/94) of participants seropositive at 1 month became seronegative at follow-up and 11% (18/165) became seropositive. The latter were mainly individuals with higher antibody levels at 1 month. Antibody levels at 3-4 months were significantly reduced in both study groups, although the decline was more pronounced in the control group. Kidney transplant recipients present poor antibody response to mRNA SARS-CoV-2 vaccination, with only 38% seropositive at 3-4 months. Nevertheless, the decay in antibody response over time is modest, and some patients may present delayed response, reaching adequate antibody levels at 3-4 months. Low seropositivity rates in this group call for investigating other immunization strategies.

Longevity of Humoral Response Six Months Following BNT162b2 Vaccine in Dialysis Patients.

Background: End-stage kidney disease substantially increases the risk of severe COVID-19. However, despite early robust immunogenicity of the mRNA-SARS-CoV-2 vaccination in patients with hemodialysis, the longevity of humoral response in this high-risk population is still unknown. Methods: A prospective cohort study aimed to evaluate the longevity of serologic response in patients with hemodialysis, compared with a control group, 6 months following the second dose of the BNT162b2 vaccine. We assessed antibody response by quantitative measurement of IgG antibodies against the receptor-binding domain of the Spike protein (anti-S1-RBD IgG). Study outcomes were defined as a seropositivity rate and log-transformed anti-S1-RBD IgG levels at 6 months, and the change in antibody levels between 3 and 6 months. Findings: The cohort included 104 patients with hemodialysis and 84 controls. At a median time of 184 days (IQR, 183-188) following the second dose of the vaccine, 83/104 (79.8%) patients with hemodialysis maintained seropositivity for the anti-S1-RBD IgG level compared to 83/84 (98.8%) in the control group (p < 0.001). The log-transformed antibody level was significantly lower in the hemodialysis group (2.23 ± 0.39 log AU/ml vs. 2.69 ± 0.65 log AU/ml, respectively, p < 0.001). Older age and hypoalbuminemia were the only variables that were found to be associated with reduced log-transformed antibody levels in univariate and multivariate analysis. There was no interaction between dialysis status and an antibody-level decline rate (p = 0.972). Conclusion: Among patients with hemodialysis, a seropositivity rate and anti-S1-RBD antibody titers were substantially reduced compared with a control group, at 6 months following the second dose of the BNT162b2 vaccine. These findings support the prioritization of patients with hemodialysis for a third "booster" dose.

Reduction of exposure to tacrolimus trough level variability is associated with better graft survival after kidney transplantation.

PURPOSE: High tacrolimus trough drug level variability was found to be associated with reduced graft survival. The primary goal of this study was to find whether reduction of exposure to high tacrolimus trough level variability in patients in which previously had high variability was associated with better graft survival. METHODS: All tacrolimus drug level values in patients that underwent kidney transplantation at our center between 2006 and 2015 were collected. Exposure to variability was calculated using a time-weighted coefficient of variability (TWCV). Time-dependent univariate and multivariate Cox proportional hazard models were used to analyze the primary outcome of graft survival and to determine a cutoff value for TWCV as a predictor of this outcome. RESULTS: A total of 878 patients were included in the study with a median follow-up of 1263 days. TWCV above 25% was significantly associated with reduced graft survival (HR3.66, 95% CI 2.3-5.8, p < 0.001). Of the 480 patients (54.7%) who had a cumulative TWCV of > 25% at a certain time during the follow-up, 110 (22.9%) later returned to a cumulative TWCV of less than 25%. Reduction of TWCV to values below 25% was associated with a hazard of graft loss that was not different from patients who had cumulative TWCV of less than 25% during the entire follow-up period (HR 1.81, 95% CI 0.71-4.62, p = 0.218 and HR 1.08, 95% CI 0.39-2.99, p = 0.780) in univariate and multivariate analyses, respectively. CONCLUSIONS: Monitoring TWCV can help detect the high-risk patients. Interventions intended to reduce variability on long-term graft survival may have a positive effect on graft survival.

Association of the combination of time-weighted variability of tacrolimus blood level and exposure to low drug levels with graft survival after kidney transplantation.

Background: The variability of tacrolimus blood levels has been shown to be associated with inferior graft survival. However, the effect of variability during the early post-transplantation period has not been evaluated. We sought to evaluate the association between time-weighted variability in the early post-transplantation period and graft survival. We also explored the interaction between drug level variability and exposure to inadequate drug levels. Methods: This retrospective cohort study included all patients who underwent kidney transplantation in the Rabin Medical Center and were treated with tacrolimus. Time-weighted coefficient of variability (TWCV) was defined as time-weighted standard deviation divided by the mean drug level. Univariate and multivariate Cox proportional hazard model was used with the primary outcome of patients and graft survival. Results: The study population included 803 patients who underwent kidney transplantation between 1 January 2000 and 29 September 2013. The high tertile of TWCV of tacrolimus blood levels was associated with reduced graft survival by univariate and multivariate analyses [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.14-2.53, P = 0.01 and HR 1.74, 95% CI 1.14-2.63, P = 0.01, respectively]. The interaction between high TWCV and exposure to inadequately low drug levels was significantly associated with reduced survival (P = 0.004), while the interaction between TWCV and high drug blood levels was not. One hundred and thirty patients (16.2%) had the combination of high TWCV and exposure to low drug values (<5 ng/mL). These patients had reduced graft survival by univariate and multivariate analyses (HR 2.42, 95% CI 1.57-3.74, P < 0.001 and HR 2.6, 95% CI 1.65-4.11, P < 0.001, respectively). Conclusions: The combination of high TWCV and exposure to low drug levels might identify high-risk patients in the early post-transplantation period.

Haemoglobin variability in the early post-transplant period: association with graft survival and mortality.

AIM: Haemoglobin (Hb) variability is associated with poor survival in patients with chronic kidney disease. Association of Hb variability after kidney transplantation with patients' and graft survival has not been adequetly studied. METHODS: This retrospective study used registry data to examine the association between Hb variability in the early post-transplant period (first 6 months) and graft survival after kidney transplantatin. Kaplan-Meier and Cox regression analyses were used for univariate and multivariate associations between mortality, death censored graft survival and the composite outcome of both, in 752 patients after kidney transplantation. Hb values were collected each month during the first 6 months after transplantation, and Hb variavility was calculated using the residual standard deviation method. RESULTS: The highest quartile of Hb variability was associated with inferior graft and patients' survival in univariate (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.51 to 3.13; P < 0.001) and multivariate models (HR 1.5; 95% CI 1.029 to 2.18; P = 0.035). This association was mainly due to increased death censored graft failure in the high variability group (HR 2.75; 95% CI 1.73 to 4.38; P < 0.001) and (HR 1.67; 95% CI 1.023 to 2.74; P = 0.04) in the univariate and multivariate models, respectively. There was no association between Hb variability and the risk of death (HR 1.51; 95% CI 0.88 to 2.57; P = 0.132). CONCLUSION: High Hb variability is independently associated with inferior graft survival in patients after kidney transplantation.

Failure to achieve early bacterial eradication increases clinical failure rate in acute otitis media in young children.

BACKGROUND: The objective of this study was to determine the association between early bacteriologic failure and clinical failure in acute otitis media (AOM). METHODS: Children with AOM aged 3-35 months enrolled in studies documenting both bacteriologic outcomes by tympanocentesis on day 4-6 and clinical outcomes on day 11-16 (immediate posttreatment visit) constituted our study group. Bacteriologic outcomes were studied for children with AOM caused by Streptococcus pneumoniae, nontypeable Haemophilus influenzae or both. The relative risk (RR) for clinical failure of children with bacteriologic failure compared with children with bacteriologic eradication was the main outcome measure. RESULTS: Nine hundred seven episodes were analyzed. Clinical failure occurred in 7.3% of 660 patients with bacterial eradication versus 32.8% of 247 patients with bacteriologic failures. The overall RR (95% confidence interval) for clinical failure was 4.41 (95% CI: 3.19-6.11), with little variation between pathogens. After correction for age, gender, ethnic origin, previous otitis history, and previous antibiotic treatment, the rate was 6.52 (95% CI: 4.26-9.99). Across clinical studies with 8 antibiotic drug regimens for AOM, the rate of clinical failure correlated with bacteriologic failure (r = 0.8967; P = 0.003). CONCLUSIONS: In young children with culture-positive AOM, failure to eradicate the pathogen from middle ear fluid within the first few days of treatment leads to a significant risk for clinical failure.