The aim of this study was to investigate whether the combination of low-dose sirolimus (SRL) and low-dose extended-release tacrolimus (TAC) compared to normal-dose extended-release TAC results in a difference in the renal function and comparable rates of rejection, graft and patient survival at 36 months after transplantation. This study was an open-label, multicenter randomized, controlled trial. Patients were randomized to once-daily normal-dose extended-release TAC (control group) or once-daily combination therapy of SRL and low-dose extended-release TAC (interventional group). The primary endpoint was the cumulative incidence of chronic kidney disease (CKD) defined as grade ≥3 (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) at 36 months after transplantation. In total, 196 patients were included. CKD at 36 months was not different between the control and interventional group (50.8%, 95% CI: 39.7%-59.9%) vs. 43.7%, 95% CI: 32.8%-52.8%). Only at 6 months after transplantation, the eGFR was higher in the interventional group compared to the control group (mean eGFR 73.1±15 vs. 67.6±16 mL/min/1.73 m2, p=0.02) in the intention-to-treat population. No differences in the secondary endpoints and the number of serious adverse events were found between the groups. Once daily low-dose SRL combined with low-dose extended-release TAC does ultimately not provide less CKD grade ≥3 at 36 months compared to normal-dose extended-release TAC.

BACKGROUND:

The rapid development and universal access to vaccines represent a milestone in combating the coronavirus disease 2019 (COVID-19) pandemic. However, there are major concerns about vaccine response in immunocompromised populations in particular transplant recipients. In the present study, we aim to comprehensively assess the humoral response to COVID-19 vaccination in both orthotopic organ transplant and allogeneic hematopoietic stem cell transplant recipients.

METHODS:

We performed a systematic review and meta-analysis of 96 studies that met inclusion criteria.

RESULTS:

The pooled rates of seroconversion were 49% (95% confidence interval [CI], 43%-55%) in transplant recipients and 99% (95% CI, 99%-99%) in healthy controls after the second dose of vaccine. The pooled rate was 56% (95% CI, 49%-63%) in transplant recipients after the third dose. Immunosuppressive medication is the most prominent risk factor associated with seroconversion failure, but different immunosuppressive regimens are associated with differential outcomes in this respect. Calcineurin inhibitors, steroids, or mycophenolate mofetil/mycophenolic acid are associated with an increased risk of seroconversion failure, whereas azathioprine or mammalian target of rapamycin inhibitors do not. Advanced age, short interval from receiving the vaccine to the time of transplantation, or comorbidities confers a higher risk for seroconversion failure.

CONCLUSIONS:

Transplant recipients compared with the general population have much lower rates of seroconversion upon receiving COVID-19 vaccines. Immunosuppressants are the most prominent factors associated with seroconversion, although different types may have differential effects.

BACKGROUND: The impact of different immunosuppression regimes on the health-related quality of life (HRQoL) and the severity of fatigue in liver transplant recipients is largely unknown. We investigated the impact of a sirolimus-based regimen compared with a tacrolimus (TAC)-based regimen on the HRQoL and the severity of fatigue. METHODS: In this multicenter, open-label, randomized, controlled trial, 196 patients were randomized 90 d after transplantation to (1) once daily normal-dose TAC or (2) once daily combination therapy of low-dose sirolimus and TAC. HRQoL was measured with the EQ-5D-5L questionnaire, the EQ-visual analog scale, and the severity of fatigue questionnaire Fatigue Severity Score (FSS). The EQ-5D-5L scores were translated to societal values. We examined the HRQoL and the FSS over the course of the study by fitting generalized mixed-effect models. RESULTS: Baseline questionnaires were available for 87.7% (172/196) of the patients. Overall, patients reported the least problems in the states of self-care and anxiety/depression and the most problems in the states of usual activities and pain/discomfort. No significant differences in HrQol and FSS were seen between the 2 groups. During follow-up, the societal values of the EQ-5D-5L health states and the patient's self-rated EQ-visual analog scale score were a little lower than those of the general Dutch population in both study arms. CONCLUSIONS: The HRQoL and FSS were comparable in the 36 mo after liver transplantation in both study groups. The HRQoL of all transplanted patients approximated that of the general Dutch population, suggesting little to no residual symptoms in the long term after transplantation. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.