Transplantology, Volume 2, Issue 2 (June 2021) – 13 articles

We report clinical features, treatments and outcomes in 18 lung transplant recipients with laboratory confirmed SARS-CoV-2 infection. We performed a single center, retrospective case series study of lung transplant recipients, who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. Clinical, laboratory and radiology findingswere obtained. Treatment regimens and patient outcome data were obtained by reviewing the electronic medical record. Mean age was 49.9 (22–68) years, and twelve (67%) patients were male. The most common symptoms were fever (n = 9, 50%), nausea/vomiting (n = 7, 39%), cough (n = 6, 33%), dyspnea (n = 6, 33%) and fatigue (n = 6, 33%). Headache was reported by five patients (28%). The most notable laboratory findings were elevated levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Computed Tomography (CT) of the chest was performed in all hospitalized patients (n = 11, 7%), and showed ground-glass opacities (GGO) in 11 patients (100%), of whom nine (82%) had GGO combined with pulmonary consolidations. Six (33%) patients received remdesivir, five (28%) intravenous dexamethasone either alone or in combination with remdesivir, and 15 (83%) were treated with broad spectrum antibiotics including co-amoxicillin, tazobactam-piperacillin and meropenem. Four (22%) patients were transferred to the intensive care unit, two patients (11%) required invasive mechanical ventilation who could not be successfully extubated and died. Eighty-nine percent of our patients survived COVID-19 and were cured. Two patients with severe COVID-19 did not survive. Full article

Large animal studies of long-term ischemia reperfusion are hampered by the use of immunosuppressive drugs to inhibit the influence of the allogeneic response. In small animals, this can be controlled by using inbred strains of the animal. For obvious reasons, this is not possible in large animals such as pigs. Since studies in pigs usually are the last step before first-in-man studies, this remains a problem trying to resemble a clinical situation. In the following short paper, we describe a novel auto kidney transplantation model that can be used for long term ischemia reperfusion studies. We also suggest a control setting to balance out the possible influence of an increased surgical trauma. Full article

Previous research suggests that effective lifestyle interventions for solid organ transplant (SOT) recipients must be tailored to address the unique life circumstances of this population. As few studies have investigated this design consideration, this study aimed to explore the perspectives and experiences of SOT recipients after completing a Group Lifestyle Balance™ [GLB]-based intervention incorporating either (a) standard population-based nutrition guidance or (b) nutrigenomics-based nutrition guidance. All active participants in the Nutrigenomics, Overweight/Obesity, and Weight Management-Transplant (NOW-Tx) pilot study were invited to participate. Data were collected through focus groups and individual interviews. Ninety-five percent (n = 18) of the NOW-Tx pilot study participants enrolled in the current study: 15 participated in 3 focus groups; 3 were interviewed individually. Three themes were common to both intervention groups: (1) the post-transplant experience; (2) beneficial program components; (3) suggestions for improvement. A unique theme was identified for the nutrigenomics-based intervention, comprising the sub-themes of intervention-specific advantages, challenges, and problem-solving. The readily available and adaptable GLB curriculum demonstrated both feasibility and acceptability and was aligned with participants’ needs and existing health self-management skills. The addition of nutrigenomics-based guidance to the GLB curriculum may enhance motivation for behaviour change in this patient population. Full article

Ischemia reperfusion injury (IRI) is one of the most important mechanisms involved in delayed or reduced graft function after kidney transplantation. It is a complex pathophysiological process, followed by a pro-inflammatory response that enhances the immunogenicity of the graft and the risk of acute rejection. Many biologic processes are involved in its development, such as transcriptional reprogramming, the activation of apoptosis and cell death, endothelial dysfunction and the activation of the innate and adaptive immune response. Recent evidence has highlighted the importance of complement activation in IRI cascade, which expresses a pleiotropic action on tubular cells, on vascular cells (pericytes and endothelial cells) and on immune system cells. The effects of IRI in the long term lead to interstitial fibrosis and tubular atrophy, which contribute to chronic graft dysfunction and subsequently graft failure. Furthermore, several metabolic alterations occur upon IRI. Metabolomic analyses of IRI detected a “metabolic profile” of this process, in order to identify novel biomarkers that may potentially be useful for both early diagnosis and monitoring the therapeutic response. The aim of this review is to update the most relevant molecular mechanisms underlying IRI, and also to discuss potential therapeutic targets in future clinical practice. Full article

Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatible living donor. The desensitization protocol consisted of Rituximab administration and immunoadsorption while the pre-transplant protocol, which was initiated 14 days before the transplant, included Tacrolimus, Mofetil Mycophenolate (MMF), antimicrobial and antiviral prophylaxis. Induction therapy consisted of anti-thymocyte globulins and steroids, while maintenance after transplantation consisted of steroid, tacrolimus and MMF. When the first occurrence of leukopenia was observed six weeks after the transplant, firstly antimicrobial/antiviral prophylaxis was stopped and later also MMF treatment was interrupted but severe neutropenia relapsed after MMF resuming treatment. Immunological and virological causes were excluded. The patient was treated with Filgrastim. Bone marrow biopsy, which was performed to exclude a hematological cause of severe persistent neutropenia, revealed a bone marrow hypoplasia with neutrophils maturation interrupted at the early stages. This case highlights the need to establish diagnostic and therapeutic guidelines for PTN which take in consideration all the therapeutic steps including the pre-transplant phase in particular in the context of AB0i where immunosuppression is more consistent. Full article

Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifying which would be the most appropriate immunosuppressive maintenance therapy. The combination of a steroid and a calcineurin inhibitor is the current immunosuppressive regimen of choice for autoimmune hepatitis. A gradual withdrawal of glucocorticoids is also recommended. On the other hand, ursodeoxycholic acid should be initiated soon after liver transplant to prevent recurrence and improve graft and patient survival in primary biliary cholangitis recipients. Unlike the previously mentioned autoimmune diseases, there are not immunosuppressive or disease-modifying agents available for patients with primary sclerosing cholangitis. However, colectomy and annual colonoscopy are key components during the post-liver transplant period. Full article

Although machine perfusion is a hot topic today, we are just at the beginning of understanding the underlying mechanisms of protection. Recently, the first randomized controlled trial reported a significant reduction of ischemic cholangiopathies after transplantation of livers donated after circulatory death, provided the grafts were treated with an endischemic hypothermic oxygenated perfusion (HOPE). This approach has been known for more than fifty years, and was initially mainly used to preserve kidneys before implantation. Today there is an increasing interest in this and other dynamic preservation technologies and various centers have tested different approaches in clinical trials and cohort studies. Based on this, there is a need for uniform perfusion settings (perfusion route and duration), and the development of general guidelines regarding the duration of cold storage in context of the overall donor risk is also required to better compare various trial results. This article will highlight how cold perfusion protects organs mechanistically, and target such technical challenges with the perfusion setting. Finally, the options for viability testing during hypothermic perfusion will be discussed. Full article

Uterus transplantation (UTx) offers women with absolute uterine factor infertility the option to gestate and birth their own biologically related child. The first birth following living donation UTx happened in 2014. The first birth following deceased donation happened in December 2017, with further successes since. Interest in deceased donation UTx is increasing. The authors established a database to track UTx clinical trials and outcomes. Utilising this database and existing literature, this article reviews the first reported cases of deceased donation UTx and outcomes, and drawing upon comparisons with living donor UTx, comments upon the future for this area of reproductive transplantation research. This is the first article to bring together the literature on deceased donation UTx procedures and outcomes. Full article

Cytomegalovirus (CMV) prophylaxis with valganciclovir is the standard of practice in most transplant centers, but treatment-related leukopenia can limit valganciclovir’s use. Therefore, we evaluated letermovir, a novel antiviral agent recently approved for use in hematopoietic cell transplant patients as CMV prophylaxis, in lung transplant recipients unable to tolerate valganciclovir due to severe leukopenia. We performed a retrospective analysis of all lung transplant patients at our center who received letermovir for CMV prophylaxis between 1 December 2018 and 1 January 2020. A repeated measures mixed model was used to analyze white blood cell (WBC) trends, and descriptive statistics were used to analyze secondary endpoints, including CMV DNAemia, renal function, immunosuppression dosing, and allograft function. Seventeen patients were administered letermovir during the study period due to valganciclovir-induced leukopenia (median WBC nadir 1.1 K/uL, range <0.30–2.19 K/uL). Median WBC improvement was noted in 15 (88.2%) patients after starting letermovir. Breakthrough CMV DNAemia necessitating treatment occurred in two patients, with one of the two cases being due to patient noncompliance. CMV resistance to letermovir was detected in two patients, necessitating a change to an alternative agent in one of these patients. No major side effects were reported in any patient. Letermovir is a generally safe and effective alternative for CMV prophylaxis in lung transplant recipients unable to tolerate valganciclovir due to leukopenia. Full article

After decades of pioneering advances and improvements, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Despite this success, the high risk of premature death and frequent occurrence of graft failure remain important clinical and research challenges. The current burst of studies and other innovative initiatives using artificial intelligence (AI) for a wide range of analytical and practical applications in biomedical areas seems to correlate with the same trend observed in publications in the kidney transplantation field, and points toward the potential of such novel approaches to address the aforementioned aim of improving long-term outcomes of kidney transplant recipients (KTR). However, at the same time, this trend underscores now more than ever the old methodological challenges and potential threats that the research and clinical community needs to be aware of and actively look after with regard to AI-driven evidence. The purpose of this narrative mini-review is to explore challenges for obtaining applicable and adequate kidney transplant data for analyses using AI techniques to develop prediction models, and to propose next steps in the field. We make a call to act toward establishing the strong collaborations needed to bring innovative synergies further augmented by AI, which have the potential to impact the long-term care of KTR. We encourage researchers and clinicians to submit their invaluable research, including original clinical and imaging studies, database studies from registries, meta-analyses, and AI research in the kidney transplantation field. Full article

Renal hypoxia has recently been implicated as a key contributor and indicator of various glomerular diseases. As such, monitoring changes in renal oxygenation in these disorders may provide an early diagnostic advantage that could prevent potential adverse outcomes. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is an emerging noninvasive technique for assessing renal oxygenation in glomerular disease. Although BOLD MRI has produced promising initial results for the use in certain renal pathologies, the use of BOLD imaging in glomerular diseases, including primary and secondary nephrotic and nephritic syndromes, is relatively unexplored. Early BOLD studies on primary nephrotic syndrome, nephrotic syndrome secondary to diabetes mellitus, and nephritic syndrome secondary to systemic lupus erythematosus have shown promising results to support its future clinical utility. In this review, we outline the advancements made in understanding the use of BOLD MRI for the assessment, diagnosis, and screening of these pathologies. Full article

Sexual life and fertility are compromised in end stage kidney disease both in men and in women. Successful renal transplantation may rapidly recover fertility in the vast majority of patients. Pregnancy modifies anatomical and functional aspects in the kidney and represents a risk of sensitization that may cause acute rejection. Independently from the risks for the graft, pregnancy in kidney transplant may cause preeclampsia, gestational diabetes, preterm delivery, and low birth weight. The nephrologist has a fundamental role in correct counseling, in a correct evaluation of the mother conditions, and in establishing a correct time lapse between transplantation and conception. Additionally, careful attention must be given to the antirejection therapy, avoiding drugs that could be dangerous to the newborn. Due to the possibility of medical complications during pregnancy, a correct follow-up should be exerted. Even if pregnancy in transplant is considered a high risk one, several data and studies document that in the majority of patients, the long-term follow-up and outcomes for the graft may be similar to that of non-pregnant women. Full article