Transplantology, Volume 3, Issue 1 (March 2022) – 11 articles

This brief communication about machine perfusion of potential human donor hearts describes its historical development. Included in the review are both the isolated perfusion of donor hearts retrieved from heart beating and non-heart-beating donors. Additionally, some detail of in-situ (within the donor body) normothermic regional reperfusion of the heart and other organs is given. This only applies to the DCD donor heart. Similarly, some detail of ex-situ (outside the body) heart perfusion is offered. This article covers the entire history of the reperfusion of donor hearts. It takes us up to the current day describing 6 years follow-up of these donor machine perfused hearts. These clinical results appear similar to the outcomes of heart beating donors if reperfusion is managed within 30 min of normothermic circulatory determined death. Future developments are also offered. These are 3-fold and include: i. the pressing need for objective markers of the clinical outcome after transplantation, ii. the wish for isolated heart perfusion leading to improvement in donor heart quality, and iii. a strategy to safely lengthen the duration of isolated heart perfusion. Full article

Throughout the years, much progress has been made in the field of renal transplantation; however, along with new developments, new problems have arisen. While transplantation is the optimal choice in patients suffering from end-stage renal disease, it is always connected to certain commonly associated risks, in particular those caused by opportunistic infections. One such risk includes the reactivation of cytomegalovirus (CMV), an issue commonly affecting all kinds of transplant recipients. Similarly, with the rise of the ever-evolving global SARS-CoV-2 pandemic, patients must be constantly monitored for any respiratory symptoms, and observed closely under the care of their attending physician. Treating these patients has become extremely difficult due to limitations caused by COVID-19 protocols (for instance, the reduction of immunosuppression dosages and the avoidance of lymphocyte-depleting induction therapy) and the lack of knowledge surrounding this relatively new and worsening risk factor. In order to give patients optimal care, these arising problems need to be studied and addressed. Full article

Waiting list mortality together, with limited availability of organs, are one of the major challenges in liver transplantation (LT). Especially in the paediatric population, another limiting factor is the scarcity of transplantable liver grafts due to additional concerns regarding graft size matching. In adults, donation after circulatory death (DCD) liver grafts have been used to expand the donor pool with satisfactory results. Although several studies suggest that DCD livers could also be used in paediatric recipients with good outcomes, their utilisation in children is still limited to a small number of reports. Novel organ perfusion strategies could be used to improve organ quality and help to increase the number of DCD grafts utilised for children. With the current manuscript, we present the available literature of LT using DCD grafts in paediatric recipients, discussing current challenges with the use of these livers in children and how machine perfusion technologies could be of impact in the future. Full article

Immunocompromised patients with respiratory viral infections are at increased risk of fungal superinfections, including Pneumocystosis. Within the scope of the COVID-19 pandemic, Pneumocystis jirovecii co-infections are being increasingly reported. Differential diagnosis often creates a dilemma, due to multiple overlapping clinical and radiographic features. Awareness of fungal co-infections in the context of the COVID-19 pandemic is crucial to initiate prophylactic measures, especially in high-risk individuals. We report the second case of Pneumocystis jirovecii pneumonia and COVID-19 co-infection in a renal transplant recipient in Poland. Full article

Kidney transplant programs have different approaches to induction immunosuppression, and conflicting data exist on the role of steroid maintenance in recipients with glomerulonephritis (GN). GN patients are unique because of a higher risk for immune system exhaustion due to prior exposure to immunosuppressants to treat their GN; this raises questions regarding the optimal immunosuppression needed for transplant success and reduction of complications. We sought to assess the effect of induction type and steroid maintenance on the recipient and kidney graft survival in those with IgA nephropathy (IgAN), systemic lupus erythematosus related GN (SLE), small-vessel vasculitis (SVV), and anti-glomerular basement membrane disease (anti-GBM). We analyzed the Scientific Registry of Transplant Recipients (SRTR) database for adult, primary kidney recipients with the above glomerulonephritides through September 2019. Kaplan–Meier curves were generated to examine kidney graft and recipient survival. We used multivariable Cox proportional hazard models to investigate the impact of induction type and steroid maintenance in each group separately. Our study included 9176 IgAN, 5355 SLE, 1189 SVV, and 660 anti-GBM recipients. Neither induction type nor steroid maintenance therapy influenced recipient or death-censored graft survival in this cohort of recipients. Our findings provide an opportunity for recipients with a history of one of the studied glomerulonephritides to receive a more tailored immunosuppression regimen, considering their previous exposure to immunosuppressants. Full article

HSCT from an unrelated HLA-mismatched donor (MMUD) is one of the alternatives where an HLA-matched donor is not found. The aim of this study was to compare GvHD prophylaxis with anti-thymocyte globulin (ATG) vs. post-transplant cyclophosphamide (PT-Cy). Thirty-nine adult patients were uniformly treated with rabbit ATG-Cy-A-MTX and peripheral blood stem cell (PBSC) and 40 adult patients with PT-Cy-MMF-tacrolimus and PBSC. This retrospective study was registered at ClinicalTrials.gov NCT04598789. Three-year overall survival was 42% vs. 64% for ATG and PT-Cy (p < 0.0005), three-year treatment-related mortality (TRM) was 36% vs. 8% (p = 0.0033) and the three-year relapse incidence (RI) was 15% vs. 28% (p = NS), respectively. The incidences of day-100 GvHD graded II–IV and III–IV were 39% vs. 7% (p = 0.0006) and 11% vs. 0% (p = 0.04), respectively, whereas the three-year cGvHD incidences were 48% vs. 13% (p = 0.0005), respectively. We were able to show how PT-Cy can reduce the incidence of GvHDs and TRM in adults, but relapse remains an issue. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global healthcare crisis. Kidney transplant (KTx) patients and the patients with chronic kidney disease are two of the most vulnerable populations to the risks of coronavirus disease 2019 (COVID-19). A systematic literature search on PubMed and Web of Science was conducted. We analyzed published case reports, case series and articles on COVID-19’s clinical presentation, management, outcomes and vaccination among kidney transplant recipients. A total of 33 studies were included in the study, which included 1676 KTx recipients and 108 waiting list patients infected with COVID-19. These studies reported the clinical presentation, management and immunosuppressive adjustment among the KTx recipients. The remaining studies focused on other aspects, such as vaccination and transplantation, during the COVID-19 pandemic. Mortality due to COVID-19 was observed to be the highest for KTx recipients, followed by patients on hemodialysis, and lowest in the general population. There is no definitive treatment of COVID-19 yet, and managing transplant patients is enigmatic of this: the treatment is based on symptom management. There is an urgent need for guidelines on managing kidney transplant recipients and immunosuppressive adjustments for the course of COVID-19 treatment. Full article

BK polyomavirus (BKV) mainly causes infection in uroepithelial and renal tubular epithelial cells of either immunocompetent or immunocompromised hosts. Despite asymptomatic or mild clinical features in immunocompetent hosts with BK infection, serious complications are frequently found in immunocompromised patients, especially patients with kidney transplantation. Accordingly, BKV-associated nephropathy (BKVN) demonstrates a wide range of clinical manifestations, including ureteric stenosis and hemorrhagic cystitis. In addition, BKV re-infection in post-kidney transplantation is also a main cause of kidney allograft dysfunction and graft loss. Since the direct anti-BKV is unavailable, immune response against BKV infection is the main mechanism for organism control and might be a novel strategy to treat or suppress BKV. As such, the innate immunity, consisting of immune cells and soluble molecules, does not only suppress BKV but also enhances the subsequent adaptive immunity to eradicate the virus. Furthermore, the re-activation of BKV in BKVN of kidney-transplanted recipients seems to be related to the status of innate immunity. Therefore, this review aims to collate the most recent knowledge of innate immune response against BKV and the association between the innate immunity status of kidney-transplanted recipients and BKV re-activation. Full article

Machine perfusion techniques are becoming standard care in the clinical donation and transplantation setting. However, more research is needed to understand the mechanisms of the protective effects of machine perfusion. For preservation related experiments, porcine kidneys are acceptable alternatives to human kidneys, because of their size and similar physiology. In this experiment, the use of slaughterhouse kidneys was evaluated with normothermic kidney perfusion (NKP), thereby avoiding the use of laboratory animals. Porcine kidneys were derived from two local abattoirs. To induce different degrees of injury, different warm ischemic times and preservation techniques were used. After preservation, kidneys were reperfused for 4 h with two different NKP solutions to test renal function and damage. The effect of the preservation technique or a short warm ischemic time was clearly seen in functional markers, such as creatinine clearance and fractional sodium excretion levels, as well as in the generic damage marker lactate dehydrogenase (LDH). Porcine slaughterhouse kidneys are a useful alternative to laboratory animals for transplantation- and preservation-related research questions. To maintain kidney function during NKP, a short warm ischemic time or hypothermic machine perfusion during the preservation phase are mandatory. Full article

Due to atrophic bladder, patients undergoing long-term dialysis experience vesicoureteral reflux and complicated urinary tract infections after kidney transplantation. A 58-year-old woman underwent living donor kidney transplantation after 41 years of dialysis. She had no contraindications, with good cardiac function and minimal artery calcification despite the long history of hemodialysis. Immunosuppression was initiated with tacrolimus, mycophenolate mofetil, prednisolone, and basiliximab. Ureteroneocystostomy with an antireflux technique was carefully conducted as her bladder volume was 15 mL. The postoperative clinical course was uneventful with immediate graft function. The bladder volume gradually increased to 81 mL at discharge, 3 weeks postoperatively. The patient was initially depressed due to frequent urination early post-transplant but recovered soon after as the bladder volume gradually increased to 400 mL. The patient has not yet reported a urinary tract infection episode. This case highlights living donor kidney transplantation-induced recovery of bladder function with careful ureteroneocystostomy, despite the long dialysis history. Full article