Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level >4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with antibody response. T-cell response was evaluated in a subset of participants. Results were compared to a control group of 56 healthcare workers. Among KTRs, we found a seropositivity rate of 70% (133/190) after the third dose (37%, 70/190, after the second vaccine dose); and 27% (52/190) achieved levels above 4160 AU/ml after the third dose, compared to 93% of controls. Variables associated with antibody response included higher antibody levels after the second dose (odds ratio [OR] 30.8 per log AU/ml, 95% confidence interval [CI]11-86.4, p < 0.001); and discontinuation of antimetabolite prior to vaccination (OR 9.1,95% CI 1.8-46.5, p = 0.008). T-cell response was demonstrated in 13% (7/53). In conclusion, third dose BNT162b2 improved immune response among KTRs, however 30% still remained seronegative. Pre-vaccination temporary immunosuppression reduction improved antibody response.

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.

Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study).

INTRODUCTION: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients. METHODS AND ANALYSIS: BECAME is a single-centre, open-label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participants per arm will be also tested for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial. ETHICS AND DISSEMINATION: The trial is approved by local ethics committee of Rabin Medical Center (RMC-0192-21). All participants will be required to provide written informed consent. Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee. TRAIL REGISTRATION NUMBER: NCT04961229.

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study.

OBJECTIVES: We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. METHODS: This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. RESULTS: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m2, 95% confidence interval (CI) 1.014-1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782-3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015-1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146-3.443, p 0.014). No serious adverse events resulting from the vaccine were reported. CONCLUSIONS: Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.

Association of obesity and muscle mass with risk of albuminuria in renal transplant recipients.

BACKGROUND: Increased albuminuria is a predictor of graft loss in kidney graft recipients. It is unknown whether obesity is an independent risk factor for the development of increased albuminuria in this population. The aim of this study was to elucidate the association between obesity and albuminuria in renal transplant recipients. METHODS: We enrolled 330 renal transplant recipients and prospectively collected demographic, anthropomorphic, clinical and laboratory variables susceptible to influence albumin excretion. The outcome was albuminuria, measured using accurately timed urine collections. Data from 201 patients were analyzed after exclusion of participants with missing data and patients enrolled less than 6 months since renal transplantation. Analysis was carried out for an early and a late period, defined according to the 2.4-year median follow-up time. RESULTS: Body mass index (BMI), waist circumference and urinary creatinine excretion rate were independent predictors of albuminuria in the late post-transplant period, indicating that the predictive value of body mass index for albuminuria is related to both increased abdominal fat mass and increased muscle mass. BMI was an independent predictor of microalbuminuria. Waist circumference and urinary creatinine were independent predictors of microalbuminuria for values above certain cutoffs: 110% of the accepted thresholds defining abdominal obesity and 1500 mg/day, respectively. CONCLUSIONS: These associations, which have not previously been reported, suggest, but do not prove, that an imbalance between metabolic demand and nephron mass may be responsible for increased albuminuria in the renal transplant population.

The urine albumin-to-creatinine ratio: assessment of its performance in the renal transplant recipient population.

BACKGROUND AND OBJECTIVES: Microalbuminuria predicts graft loss and death in the renal transplant population. Measurement of the urinary albumin-to-creatinine ratio (UACR) is recommended for its detection. There is uncertainty regarding the optimal UACR cutoff values. Few studies have examined the accuracy of UACR in the general population and none have been conducted in renal transplant recipients. The aim of this study is to determine the performance of UACR in the renal transplant population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Renal transplant recipients with a daily urinary albumin excretion rate of up to 300 mg accurately carried out a 24-hour urine collection and provided a morning urine sample for the measurement of albuminuria and UACR. The performance measures of UACR for the detection of microalbuminuria (30 to 300 mg/d) were calculated using different cutoffs. RESULTS: Median albuminuria was 23 mg/d, and median UACR was 17 mg/g. The area under the receiver-operating characteristic curve was 0.94 in men and 0.98 in women. The optimal cutoff was 21 mg/g in men and 24 mg/g in women. In men, the 30-, 17-, and 21-mg/g cutoffs provided a sensitivity of 0.79, 0.89, and 0.87. In women, the 30-, 25-, and 24-mg/g cutoffs provided a sensitivity of 0.90, 0.97, and 1.0. CONCLUSIONS: These data show that in the renal transplant population, lower gender-specific cutoffs should be used for the detection of microalbuminuria than the recommended 30-mg/g cutoff. These data support the need for a reappraisal of the 30-mg/g cutoff for the detection of microalbuminuria.