Transplantology, Volume 3, Issue 3 (September 2022) – 6 articles

Basiliximab (BAS) is an interleukin-2 monoclonal antibody initially used as induction therapy after liver and kidney transplantation. BAS use after lung transplantation (LTx) has supplanted antithymocyte globulin (ATG) as the main induction immunosuppression over the years, but few studies have compared them. In this study, we aimed to compare the efficacy and safety between BAS and ATG in LTx. We performed a retrospective analysis of all LTx done in Portugal between January 2016 and December 2019. Three groups were made according to the initial induction status: BAS, ATG or no induction (NI). The occurrences of cytomegalovirus (CMV) infection, pneumonia, side effects, primary graft dysfunction (PGD), acute rejection, chronic allograft disfunction (CLAD) and death episodes were assessed during two years after LTx. A total of 124 patients were divided in 3 groups: 61 (49.2%) BAS; 43 (34.7%) ATG; 20 (16.1%) NI. The incidences of pneumonia and CMV were similar between induction groups. Additionally, there was no difference between the induction groups in PGD, acute rejection, CLAD, deaths and two-year survival. Side effects were reported only in ATG group (n = 20; 46.5%). In our study, BAS had a better safety profile than ATG in LTx with a similar efficacy. Full article

Background: Early reports of COVID-19 in lung transplant recipients (LTRs) showed high hospitalization and mortality rates. However, the outcomes of COVID-19 in LTRs since the advent of newer therapies and vaccines have been poorly defined. Methods: We evaluated the risks for SARS-CoV-2-related hospitalization and mortality in a cohort of LTRs at the Henry Ford Lung Transplant Program in Detroit, Michigan during the study period March 2020–March 2022. Univariate logistic regression, followed by multivariable modeling were performed to estimate the odds ratio (OR) with 95% confident intervals (CI). Results: Sixty-four laboratory-confirmed SARS-CoV-2 infections were identified in 59 patients. For the primary analysis of the hospitalization and mortality risks, we included these 59 patients with symptomatic COVID-19. SARS-CoV-2 infections were confirmed with real-time polymerase chain reaction (RT-PCR) from a nasopharynx swab. The mean age (±STD) was 61 (±12), 63% were males, 27% were African Americans, and the time from lung transplant to COVID-19 was 5.5 (±4.8) years. Thirty-four (57.6%) patients were hospitalized, and the inpatient mortality rate was 24% (8/34). A multivariable analysis showed that patients with a higher baseline forced expiratory volume (FEV1) were less likely to be hospitalized (OR = 0.91 and 95% CI 0.87–0.98, p = 0.02). Seventy-five percent (75%; 6/8) of patients on invasive mechanical ventilation died, compared with only 8% mortality rate in those without mechanical ventilation (OR = 36.0 and 95% CI 4.2–310.4, p < 0.01). Although a trend toward a higher risk of death was observed in those infected during the Alpha (p = 0.17) and Delta (p = 0.22) waves, no significant risk was detected after adjusting for other covariates. Five LTRs were diagnosed with COVID-19 twice. Thirty of the sixty-four COVID-19 cases (46.8%) occurred in LTRs that had received at least two doses of any of the available mRNA vaccines at a median of 123 days (IQR 98–164 days) after vaccination. Twelve of the thirty (40%) were hospitalized, and four patients (33%) died during their hospitalizations. Conclusions: In our LTR population, the hospitalization and mortality rates associated with COVID-19 were high despite the increased use of new therapies. Vaccine-breakthrough infections were common and were associated with poor outcomes. Studies are needed to determine optimal prevention and therapeutic strategies to improve COVID-19 outcomes in LTRs. Full article

The three most common modalities of graft surveillance in pediatric heart transplant (HT) recipients include echocardiography, coronary angiography, and endomyocardial biopsy (EMB). The survival outcomes after HT in children have improved considerably in recent years. However, allograft rejection and cardiac allograft vasculopathy remain the leading cause of death or re-transplantation. The routine surveillance by EMB and coronary angiography are invasive and risky. Newer noninvasive echocardiographic techniques, including tissue Doppler imaging (TDI), 2-D speckle tracking echocardiography, CT coronary angiography (CTCA), cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) and invasive techniques such as intravascular ultrasound (IVUS), functional flow reserve (CFR) of coronary arteries, optical coherence tomography (OCT), have emerged as powerful tools which may help early recognition of sub-clinical rejection, response to treatment, early detection, and progression of CAV. The multimodality imaging approach, including noninvasive and invasive tests, is the future for the transplanted heart to detect dysfunction, rejections, and early CAV. This review illustrates noninvasive and invasive imaging techniques currently used or could be considered for clinical use in detecting heart transplant rejection, dysfunction, and CAV in children. Full article

COVID-19 can be associated with lung fibrosis. Although lung fibrosis after COVID-19 is a relatively rare finding, the mere fact that globally a very large number of patients have had COVID-19 leads to a significant burden of disease. However, patients with COVID-19-associated lung fibrosis have different clinical and radiological features. The aim of this review is to define the different phenotypes of COVID-19-associated lung fibrosis, based on the medical literature. We found that two phenotypes have emerged. One phenotype is COVID-19-related acute respiratory distress syndrome (CARDS); the other phenotype is post-COVID-19 pulmonary fibrosis (PCPF). Both phenotypes have different risk factors, clinical, and radiological features, and differ in their pathophysiological mechanisms and prognoses. A long-term follow-up of patients with pulmonary complications after COVID-19 is warranted, even in patients with only discrete fibrosis. Further studies are needed to determine the optimal treatment because currently the literature is scarce, and evidence is only based on small case series or case reports. Full article

Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers, however, have adopted an early antimetabolite withdrawal in addition to other interventions. The epidemiological problem concerns also dialysis patients and waitlisted patients who have a higher COVID-19 infection diffusion with respect to kidney transplant recipients. Several factors influence mortality among kidney transplant recipients. Among these factors are the age, race, and comorbidity factors, such as hypertension, diabetes mellitus, obesity, and previous respiratory problems. Treatment is still limited. The only effective antiviral drug is remdesivir that should be administered before the development of the cytokine storm. Vaccination seems to be useful, but due to the concomitant immunosuppression limiting its efficacy, at least three or four doses should be administered. Full article

The use of novel oral anticoagulants in patients with impaired renal function or undergoing immunosuppressive therapy is limited due to the risk of drug-to-drug interactions and anticoagulation-related adverse events. This article aims to assess the current data on the safety of direct-acting oral anticoagulant-based therapy in the population of kidney transplant recipients and patients with impaired renal function. The most important factors affecting the safety of treatment are the incidence of bleeding events, thromboembolic events, deaths and drug-to-drug interactions. The available data were compared to the findings on warfarin-based anticoagulation. Findings on the use of novel oral anticoagulants in kidney transplant recipients are limited yet promising in terms of safety and efficacy of use. However, current recommendations state that the co-administration of non-vitamin K antagonist oral anticoagulants with several immunosuppressive agents is contraindicated. Full article