Human leukocyte antigen antibody sensitization, lung transplantation, and health equity.

Women with advanced lung disease, particularly Black and Hispanic women, are more likely than other patients to have anti-human leukocyte (HLA) antibodies against potential donors. Sensitized patients, especially those who are highly sensitized, are less likely to be listed for lung transplant or to be considered candidates for mechanical circulatory support. They are also at higher risk for waitlist death. Institutional variability in approach to HLA antibody screening and pre-transplant management creates barriers to transplant that disproportionately impact Black and Hispanic women. At the same time, our understanding of the clinical significance of pre-transplant antibodies lags behind the sophistication of our screening assays. The lack of national data on pre- and post-transplant HLA antibody characteristics hinders research into strategies to mitigate concerns about these antibodies and to improve access to lung transplant among sensitized patients. Ongoing work should be done to identify clinically higher risk antibodies, to develop better strategies for safely crossing antibodies at the time of transplant, and to model changes in lung allocation to give priority to sensitized patients for a HLA antibody-antigen compatible donors. These priorities mandate a commitment to collaborative, multicenter research and to real time translation of results to clinical practice and allocation policy.

The clinical value of donor-derived cell-free DNA measurements in kidney transplantation.

Early diagnosis is critical to minimizing the damage rejection can do to the transplanted kidney. Donor-derived cell-free DNA (dd-cfDNA) represents non-encapsulated fragmented DNA that is continuously shed into the bloodstream from the allograft undergoing injury, with a half-life of about 30 min. This article reviews the available evidence regarding the diagnostic value of dd-cfDNA in kidney transplantation, as a result of which two assays, Allosure and Prospera, have garnered Medicare approval. We provide information on important scenarios and contexts including antibody-mediated rejection, T-cell mediated rejection, pre-test probability of rejection, timing of the test, repeat transplants, and background cell-free DNA levels to help our understanding of the test characteristics and utility of these assays in clinical practice. Data on multimodality assays including gene expression profiles and serial monitoring of dd-cfDNA in high risk situations are emerging.

Immunologic Risk Assessment and Approach to Immunosuppression Regimen in Kidney Transplantation.

The outcomes of kidney transplantation show a steady improvement with an increasing number of transplantations and decreasing incidence of acute rejection episodes. Successful transplantation begins with a comprehensive immunologic risk assessment and judicious choice of therapeutic agents. In this review, we discuss the trends in transplant immunosuppression practices and outcomes in the United States. We discuss practical testing algorithms for clinical decision making in induction therapy and fine-tuning maintenance immunosuppression. We introduce assessment tools for immune monitoring after transplantation and speculate on future directions in management.

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity.

PURPOSE OF REVIEW: This review highlights the current literature on both infectious and noninfectious diarrhea in renal transplant recipients and provides a diagnostic algorithm for the evaluation of posttransplant diarrhea. RECENT FINDINGS: Renal transplant recipients share certain predisposing characteristics for the development of posttransplant diarrhea, including a generalized immunosuppressed state and exposure to polypharmacy, most notably broad-spectrum antimicrobial therapy. The main causes of diarrhea after transplantation are infections, immunosuppressive drugs, antibiotics and other drugs. As the cause of posttransplant diarrhea varies greatly depending on several factors, recommending a single optimal diagnostic algorithm is extremely difficult. SUMMARY: Physicians should be familiar with common causes that result in posttransplant diarrhea. A directed approach to diagnosis and treatment will not only help to resolve diarrhea, but also prevent potentially life-threatening consequences, such as loss of the graft. Prospective studies are needed to better assess true prevalence, risk factors and complications of diarrhea by norovirus, rotavirus and adenovirus in kidney transplant patients.