A Complement to Traditional Treatments for Antibody-Mediated Rejection? Use of Eculizumab in Lung Transplantation: A Review and Early Center Experience.

OBJECTIVE: To review the efficacy and safety of eculizumab for prevention and treatment of antibody-mediated rejection (AMR) in lung transplant recipients (LTRs). DATA SOURCES: A literature search of PubMed and the Cochrane Controlled Trials Register (2007 to mid-October 2023) was performed using the following search terms: eculizumab, complement inhibitor, solid organ transplant, lung transplant, and AMR. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language studies were reviewed and considered. DATA SYNTHESIS: Eculizumab, a monoclonal antibody that binds complement protein C5 to inhibit its cleavage and subsequent generation of the membrane attack complex, is currently approved to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia and neuromyelitis optica spectrum disorder. Given the role of antibodies directed against donor antigens that are produced by allospecific B-cells and plasma cells in AMR, eculizumab is being investigated for use within this indication. Three case reports have described the successful use of eculizumab for the prevention and treatment of AMR in LTRs. Given this lack of robust data, evidence for the use of eculizumab in other solid organ transplant recipients is of increased value. Early experiences from a single center's use of eculizumab in LTRs are also described. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Lung transplant is a recognized treatment for end-stage lung disease, though complications posttransplant can be associated with significant morbidity and mortality. While prevention and management of AMR remains a substantial challenge without comprehensive guidance from societal guidelines, recently published literature may be helpful to guide clinical practice using alternative treatment options. However, this remains an area of great clinical importance, given the impact of AMR on long-term allograft function. CONCLUSIONS: Optimizing use of current therapies, as well as identifying and advancing novel therapeutic modalities such as eculizumab, are vital for the improvement of AMR prevention and treatment in LTRs to extend long-term allograft function and survival.

Outcomes of Children with Fetal and Lactation Immunosuppression Exposure Born to Female Transplant Recipients.

Solid organ transplantation (SOT) is a lifesaving procedure for those with end-stage kidney, liver, heart, lung, and intestinal diseases, including females of childbearing age who wish to proceed with pregnancy following transplantation. While there is clear risk associated with use of mycophenolate during pregnancy, the risks associated with use of other immunosuppressant agents are less well understood, and the timing of use in pregnancy may be pertinent when considering the risk versus benefit for individual patients. In addition to overall fetal outcomes, including gestational age, birth weight, and mortality, this review summarizes published literature on additional complications that have been examined in association with maternal use during pregnancy and postpartum while breastfeeding. Compared with non-transplant pregnancies, pregnancies in transplant recipients are associated with lower birth weight and earlier gestational age. Effects associated with particular immunosuppressant agents in the infant include renal dysfunction from calcineurin inhibitors, myelosuppression from azathioprine, and decreased circulating immune cells with several agents. However, these effects are noted to primarily be transient, though the decrease in immune cells may predispose the infant to increased infectious complications in the first year of life. Utilizing relative infant dose estimations, nearly all commonly utilized immunosuppressants are likely safe during breastfeeding given the limited exposure to the infant.

Evaluation of anti-factor Xa concentrations using a body mass index-based enoxaparin dosing protocol for venous thromboembolism prophylaxis in trauma patients.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a body mass index (BMI)-based enoxaparin prophylaxis dosing protocol at achieving target anti-factor Xa (anti-Xa) concentrations in the trauma population. METHODS: This retrospective chart review evaluated anti-Xa concentrations in adult trauma patients who received prophylactic enoxaparin over a three-month period. The primary outcome was the percentage of patients that achieved target anti-Xa concentrations after ≥3 doses of enoxaparin. Secondary outcomes included correlations of anti-Xa concentrations with enoxaparin dose per BMI, total body weight (TBW), and estimated blood volume (EBV). The prevalence of clinically relevant bleeding and venous thromboembolism was also recorded. Multivariable logistic regression was used to identify associated variables for target anti-Xa concentration attainment. RESULTS: Ninety-nine consecutive patients were included in the study. Included patients were predominately male (69.7%) and Black (50.5%) with a mean age of 44.1 years. Target anti-Xa concentrations were achieved in 62.6% of patients. Anti-Xa concentrations were moderately correlated with enoxaparin dose per EBV (ρ = 0.57), followed by dose per TBW (ρ = 0.46), and dose per BMI (ρ = 0.20). Multivariable logistic regression demonstrated that categorization of enoxaparin dose per EBV and per TBW were the only statistically significant predictors of reaching target anti-Xa concentrations (p = <0.001). CONCLUSIONS: In adult trauma patients, the rate of achieving target anti-Xa concentrations remains suboptimal and provides room for further improvement. Enoxaparin dose per EBV was more closely correlated with anti-Xa concentrations when compared to TBW and BMI. Dosing per EBV and TBW was the only variables associated with reaching target anti-Xa concentrations within the study. Further investigation is warranted to elucidate optimal EBV- and TBW-based dosing regimens.

Persistent BK polyomavirus-DNAemia may warrant cystoscopy to rule out urologic carcinoma: A case report and review of the literature.

There is minimal literature describing the clinical workup of patients with persistent BKPyV-DNAemia despite aggressive immunosuppressive reduction. We present a case herein of persistent BKPyV-DNAemia with significant discordance of BK viruria level in a kidney transplant recipient found to have bladder carcinoma. Based on our findings, we recommend evaluating the urine of patients with persistent BKPyV-DNAemia for BK viruria. If there is significant discordance in the level of BKPyV-DNAemia and viruria, cystoscopy should be pursued to rule out bladder or uroepithelial malignancies.