Immunosuppressive therapy and oral anticoagulation in kidney transplant recipients: Direct oral anticoagulants versus vitamin-k antagonists.

BACKGROUND: direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. AIM OF THIS STUDY: evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. METHODS: a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. RESULTS: Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). CONCLUSION: DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed.

Kinetics of humoral immune response and severity of infection after three doses of SARS-CoV-2 mRNA vaccine in a large cohort of kidney transplant recipients.

BACKGROUND: COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients. METHODS: We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022. A subset of 336 patients, who received three-doses of SARS-CoV-2 vaccine, was analyzed in terms of kinetics of humoral immune response and compared to a control group of 94 healthcare workers. Antibody response was tested before vaccination (T0), 15 and 90 days after the second dose (T1 and T2), on the day of the third dose (T3) and one month after the third dose (T4). RESULTS: We observed that 66 out of 743 subjects had COVID-19 infection pre-vaccination: 65.2% had severe symptoms, 27.3% were hospitalized (9 deaths), none were asymptomatic. After three doses, 51 patients had COVID-19 infection, 60.8% were asymptomatic, 27.5% reported mild symptoms, 3.9% showed severe symptoms, 7.8% were hospitalized (2 deaths). In the subset of 336 vaccinated patients, an antibody level > 0.8 U/ml was detected at T1, that increased at T2 and T3, peaking at T4. Independent factors associated with a negative antibody titer at T4 were decreasing estimated glomerular filtration rate, time from transplantation, and antimetabolites (all p < 0.001) and age (p = 0.007). CONCLUSIONS: The kinetics of humoral response after three doses of vaccine in kidney transplant patients is characterized by a late but effective immune response against SARS-CoV-2, reducing morbidity and mortality.