Recurrent Treatment of Refractory Acute Cellular Rejection with Alemtuzumab after Lung Transplantation.

We present an exceptional case of a lung transplant recipient successfully treated by multiple courses of alemtuzumab for refractory acute cellular rejection. The patient experienced multiple episodes of acute cellular rejection following the transplantation procedure. Alemtuzumab was initiated as third-line rejection treatment and was repeated six times. Each treatment course resulted in complete recovery of the pulmonary function and depletion of T- and B-lymphocytes and NK cells. The onset of rejection was consistently preceded by the recovery of NK cells, while T- and B-lymphocytes remained depleted. This suggests a rejection process mediated by NK cells. This case contributes to recent research findings suggesting that NK cells play a significant role in acute cellular rejection in lung transplant recipients and stresses the importance to further investigate the role of NK cells in rejection. Furthermore, it demonstrates that acute cellular rejection following lung transplantation can be repeatedly managed by treatment with alemtuzumab. DATA AVAILABILITY STATEMENT: The authors confirm that the data supporting the findings of this study are available within the article.

Challenges for the improvement of valganciclovir prophylaxis in solid organ transplantation and the possible role of therapeutic drug monitoring in adults.

Cytomegalovirus (CMV) infection frequently occurs after solid organ transplantation and is associated with an increased morbidity and mortality. Fortunately, the development of valganciclovir prophylaxis has lowered the incidence of CMV infection and its complications in immunosuppressed solid organ transplant recipients. However, breakthrough infections during valganciclovir prophylaxis and late CMV infection after cessation of valganciclovir prophylaxis still occur with the current prophylactic strategy. Additionally, valganciclovir resistance has emerged among CMV strains, which complicates the treatment of CMV infections. Furthermore, the use of valganciclovir is associated with myelotoxicity, which can lead to the premature withdrawal of prophylaxis. It is important to address these current issues in order to improve the standard care after solid organ transplantation. This paper will therefore discuss the clinical practice of valganciclovir prophylaxis, elaborate on its issues and suggest how to improve the current prophylactic strategy with a possible role for therapeutic drug monitoring.

A Decade of Experience With Alemtuzumab Therapy for Severe or Glucocorticoid-Resistant Kidney Transplant Rejection.

Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of alemtuzumab therapy are unclear. Therefore, all cases of alemtuzumab anti-rejection therapy between 2012 and 2022 in our institution were investigated. Graft survival, graft function, lymphocyte depletion, serious infections, malignancies, and patient survival were analyzed and compared with a reference cohort of transplanted patients who did not require alemtuzumab anti-rejection therapy. A total of 225 patients treated with alemtuzumab were identified and compared with a reference cohort of 1,668 patients. Over 60% of grafts was salvaged with alemtuzumab therapy, but graft survival was significantly poorer compared to the reference cohort. The median time of profound T- and B lymphocyte depletion was 272 and 344 days, respectively. Serious infection rate after alemtuzumab therapy was 54.1/100 person-years. The risk of death (hazard ratio 1.75, 95%-CI 1.28-2.39) and infection-related death (hazard ratio 2.36, 95%-CI 1.35-4.11) were higher in the alemtuzumab-treated cohort. In conclusion, alemtuzumab is an effective treatment for severe kidney transplant rejection, but causes long-lasting lymphocyte depletion and is associated with frequent infections and worse patient survival outcomes.

Investigational drugs for the treatment of kidney transplant rejection.

INTRODUCTION: Kidney transplant rejection remains an important clinical problem despite the development of effective immunosuppressive therapy. Two major types of rejection are recognized, T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), which have a different pathophysiology and are treated differently. Unfortunately, long-term outcomes of both TCMR and ABMR remain unsatisfactory despite current therapy. Hence, alternative therapeutic drugs are urgently needed. AREAS COVERED: This review covers novel and investigational drugs for the pharmacological treatment of kidney transplant rejection. Potential therapeutic strategies and future directions are discussed. EXPERT OPINION: The development of alternative pharmacologic treatment of rejection has focused mostly on ABMR, since this is the leading cause of kidney allograft loss and currently lacks an effective, evidence-based therapy. At present, there is insufficient high-quality evidence for any of the covered investigational drugs to support their use in ABMR. However, with the emergence of targeted therapies, the potential arises for individualized treatment strategies. In order to generate more high-quality evidence for such strategies and overcome the obstacles of classic randomized controlled trials, we advocate the implementation of adaptive trial designs and surrogate clinical endpoints. We believe such adaptive trial designs could help to understand the risks and benefits of promising drugs such as tocilizumab, clazakizumab, belimumab, and imlifidase.

[Acute kidney injury, an avoidable problem]. / Acute nierschade, een vermijdbaar probleem.

OBJECTIVE: To analyse the incidence, risk factors and avoidability of acute kidney injury in adult patients admitted to a Dutch hospital. DESIGN: Retrospective cohort study. METHOD: We assessed all consecutive admissions in our clinic during one week for the development of acute kidney injury and its cause. We compared medical information between patients with and without acute kidney injury to identify risk factors. We reviewed whether the current advice on kidney injury was followed to estimate the avoidability of acute kidney injury. RESULTS: 347 patients were older than 18 years and admitted for more than 1 day. Acute kidney injury occurred in 16.4% of patients. Almost half of the patients already developed acute kidney injury at home, before admission. Acute kidney damage was encountered in all medical specialties. Chronic kidney disease, diabetes mellitus and heart failure were significantly more common in patients with acute kidney injury. Patients with acute kidney injury used significantly more RAS-inhibitors and loop diuretics. The renal function completely restored in half of cases. Two thirds of acute kidney injury was probably avoidable if volume depletion had been optimized or medication with hemodynamic effects had been adjusted in time according to the guidelines. CONCLUSION: Acute kidney injury is not only a common and underestimated problem in the daily practice of all doctors, but it is also probably avoidable. Awareness of the risk of acute kidney injury by doctors, pharmacists and patients can contribute to the reduction of acute kidney injury and its serious consequences.