Innate Immunity Response to BK Virus Infection in Polyomavirus-Associated Nephropathy in Kidney Transplant Recipients

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.

Development of a Porcine Slaughterhouse Kidney Perfusion Model

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.

Living Donor Kidney Transplantation for a Recipient after 41 Years of Hemodialysis

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.

An Eight-Year Followup Study after Heart Transplantation: The Relevance of Psychosocial and Psychiatric Background

A heart transplantation (HT) is performed when a patient’s heart health has been severely compromised. However, the health care needs of a patient throughout the transplantation process are also significant. In order to investigate these postoperative heart transplant challenges, this study has two objectives: to find which psychosocial and psychiatric variables relate to good prognosis at the end of the followup period and to assess cognitive status and quality of life at the end of the study. Therefore, we divided the sample according to the completion success and then studied and compared the differences in participants’ personality, coping mechanisms, locus of control, clinical, and epidemiological information. Cognitive function and quality of life assessments were also undertaken for participants who completed their followup period. Higher significant differences were found in openness to experience (personality), self-perceived support (locus of control), and positive reinterpretation (coping) among those who completed the followup period. On the other hand, a higher age and current or historical psychiatric diagnoses were more prevalent in the group who did not complete the followup period. Our assessment of the participants after the followup period showed normal levels of cognitive function and quality of life.

A Retrospective Review of Calcineurin Inhibitors’ Impact on Cytomegalovirus Infections in Lung Transplant Recipients

Immunosuppressive therapy reduces the risk for allograft rejection but leaves recipients susceptible to infections. Cytomegalovirus (CMV) is one of the most frequent causes for infection after transplantation and increases the risk for allograft rejection. As lung transplant recipients (LTRs) need to be under immunosuppression for life, they are a vulnerable group. To determine the potential association between the development of CMV infection and the calcineurin inhibitor (CNI) blood levels within previous 90 days, a retrospective review of LTRs was performed. Data from recipients who underwent a lung transplantation (LTx) at our center from January 2011 to December 2018 were collected. The studied recipients, after case/control matching, included 128 CMV-infection cases. The median time from the transplant to the first positive CMV viral load was 291.5 days. In our study, more patients were treated with tacrolimus (91.9%) than with cyclosporine (8.1%). Drug blood levels at selected timepoints showed no statistically significant difference between cases and controls. However, we found that CMV infection was more frequent in the donor-seropositive/recipient-seronegative group, interstitial lung disease (ILD) recipients, LTRs who underwent basiliximab induction, cyclosporine treated recipients, and LTRs with lymphopenia (at the time of CMV infection and 90 days before). In this review of LTRs, no association between the CNI blood level and CMV infection was seen, although other immunity-related factors were found to be influencing, i.e., basiliximab induction, cyclosporine treatment, and lymphopenia.

Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.

Laparoscopic Living-Donor Nephrectomy of a Horseshoe Kidney: A Case Report and Review of the Literature

We present the case of a living-donor nephrectomy of a horseshoe kidney. The recipient was a 33-year-old male with a history of end-stage renal disease secondary to IgA nephropathy. The donor was his 33-year-old partner who on preoperative cross-sectional imaging was found to have a horseshoe kidney with a single artery, vein and ureter. The donor operation was performed using a laparoscopic hand-assisted technique with transection of the interpolar fibrotic band using a stapler device. The backtable organ preparation was performed in a standard fashion with addition of a reinforcing hemostatic suture of the stapled fibrotic band. The donated kidney was transplanted extraperitoneally in the right iliac fossa of the recipient. The patient had an unremarkable postoperative course and was discharged home on post operative day 2 with normalizing renal function. To our knowledge, this is the first living donor nephrectomy of a horseshoe kidney performed using a laparoscopic hand-assisted technique.

Strategies to Improve Immune Suppression Post-Liver Transplantation: A Review

Since the first liver transplantation operation (LT) in 1967 by Thomas Starzl, efforts to increase survival and prevent rejection have taken place. The development of calcineurin inhibitors (CNIs) in the 1980s led to a surge in survival post-transplantation, and since then, strategies to prevent graft loss and preserve long-term graft function have been prioritized. Allograft rejection is mediated by the host immune response to donor antigens. Prevention of rejection can be achieved through either immunosuppression or induction of tolerance. This leads to a clinical dilemma, as the choice of an immunosuppressive agent is not an easy task, with considerable patient and graft-related morbidities. On the other hand, the induction of graft tolerance remains a challenge. Despite the fact that the liver exhibits less rejection than any other transplanted organs, spontaneous graft tolerance is rare. Most immunosuppressive medications have been incriminated in renal, cardiovascular, and neurological complications, relapse of viral hepatitis, and recurrence of HCC and other cancers. Efforts to minimize immunosuppression are directed toward decreasing medication side effects, increasing cost effectiveness, and decreasing economic burden without increasing the risk of rejection. In this article, we will discuss recent advances in strategies for improving immunosuppression following liver transplantation.

Stem-Cell Transplantation in Adult Patients with Relapsed/Refractory Hodgkin Lymphoma

Although the majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy, in 85–90% of early stage and 70–80% of advanced-stage disease cases, relapse remains a major problem. Autologous stem-cell transplantation (auto-HCT) after salvage chemotherapy is currently considered to be the standard of care for patients who relapse after first-line chemotherapy or for whom first-line treatment fails. The curative capacity of auto-HCT has been improving with the introduction of new drug-based salvage strategies and consolidation strategies after auto-HCT. Allogeneic stem-cell transplantation (allo-HCT) represents a reasonable treatment option for young patients who relapse or progress after auto-HCT and have chemosensitive disease at the time of transplantation. Allo-HCT is a valid treatment strategy for patients with relapse/refractory HL (r/r HL) because the results have improved over time, mainly with the safe combination of allo-HCT and new drugs. Bearing in mind that outcomes after haploidentical stem-cell transplantation (haplo-HCT) are comparable with those for matched sibling donors and matched unrelated donors, haplo-HCT is now the preferred alternative donor source for patients with r/r HL without a donor or when there is urgency to find a donor if a matched related donor is not present. The development of new drugs such as anti-CD 30 monoclonal antibodies and checkpoint inhibitors (CPI) for relapsed or refractory HL has demonstrated high response rates and durable remissions, and challenged the role and timing of HCT. The treatment of patients with HL who develop disease recurrence or progression after allo-HCT remains a real challenge and an unmet need.

Animal Models in Allogenic Solid Organ Transplantation

Animal models provide the link between in vitro research and the first in-man application during clinical trials. They provide substantial information in preclinical studies for the assessment of new therapeutic interventions in advance of human clinical trials. However, each model has its advantages and limitations in the ability to imitate specific pathomechanisms. Therefore, the selection of an animal model for the evaluation of a specific research question or evaluation of a novel therapeutic strategy requires a precise analysis. Transplantation research is a discipline that largely benefits from the use of animal models with mouse and pig models being the most frequently used models in organ transplantation research. A suitable animal model should reflect best the situation in humans, and the researcher should be aware of the similarities as well as the limitations of the chosen model. Small animal models with rats and mice are contributing to the majority of animal experiments with the obvious advantages of these models being easy handling, low costs, and high reproductive rates. However, unfortunately, they often do not translate to clinical use. Large animal models, especially in transplantation medicine, are an important element for establishing preclinical models that do often translate to the clinic. Nevertheless, they can be costly, present increased regulatory requirements, and often are of high ethical concern. Therefore, it is crucial to select the right animal model from which extrapolations and valid conclusions can be obtained and translated into the human situation. This review provides an overview in the models frequently used in organ transplantation research.