Improving the histologic detection of DSA-negative antibody-mediated rejection in kidney transplants.

Emerging treatments for antibody-mediated rejection (ABMR, NEJM391(2):122-132) have increased the importance of ABMR detection when donor-specific antibody (DSA) is negative. We addressed this issue in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703) using three centralized tests in 690 kidney transplant biopsies: DSA (One Lambda Inc.

Management recommendations for kidney transplantation in patients with plasma cell dyscrasia.

Patients with plasma cell dyscrasia, including multiple myeloma, AL amyloidosis, and monoclonal gammopathy of renal significance, face a high burden of end-stage kidney disease, which limits survival and quality of life. Although kidney transplant offers potential benefits, it remains underused because of the high risk of recurrence and historically poor outcomes. A multidisciplinary panel of transplant nephrologists, hematologists/oncologists, and pathologists convened to evaluate contemporary evidence and evolving strategies in kidney transplant for plasma cell dyscrasias and end-stage kidney disease.

Merkel Cell Carcinoma in Solid Organ Transplant Recipients: Prognosis and Response to Immunotherapy.

Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with an increased risk of occurrence in immunocompromised patients, including solid organ transplant recipients (SOTR). As the number of SOTR rises worldwide, MCC cases in this population are also expected to increase. While anti-programmed death-(ligand)1 (anti-PD-(L)1) immunotherapy generates durable tumor responses in ∼50% of immunocompetent (IC) patients with advanced MCC, its efficacy and safety in SOTR remain uncertain as these patients have been excluded from most clinical trials.

A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes.

Background: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.

Methods: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.

Real-world evidence regarding cancer, mortality, and graft failure risk with de novo belatacept use among kidney transplant recipients in the United States.

Belatacept is a selective T cell costimulation blocker used in maintenance immunosuppression for kidney transplant recipients (KTRs), but evidence on cancer risk and other outcomes is limited. This retrospective cohort study used linked US transplant and cancer registry data on KTRs treated with belatacept (N = 1514) or tacrolimus (N = 7570) as initial maintenance therapy. We used multivariable Cox regression models to compare the incidence of invasive cancer, cutaneous squamous cell carcinoma, posttransplant lymphoproliferative disorder (PTLD), death, and graft failure/retransplantation (GF/RT) between belatacept and tacrolimus users.

Serum and urine nucleic acid screening tests for BK polyomavirus-associated nephropathy in kidney and kidney-pancreas transplant recipients.

Background: BK polyomavirus-associated nephropathy (BKPyVAN) occurs when BK polyomavirus (BKPyV) affects a transplanted kidney, leading to an initial injury characterised by cytopathic damage, inflammation, and fibrosis. BKPyVAN may cause permanent loss of graft function and premature graft loss. Early detection gives clinicians an opportunity to intervene by timely reduction in immunosuppression to reduce adverse graft outcomes.

Cure models, survival probabilities, and solid organ transplantation for patients with colorectal cancer.

A previous cancer diagnosis can preclude patients from consideration for solid organ transplantation. Statistical models may improve candidate selection. We fitted statistical cure models and estimated 5-year cancer-specific survival (5yCSS) for colorectal cancer patients in the United States using registry data.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations.

Transplant Onconephrology: An Update.

Transplant onconephrology is a growing specialty focused on the health care of kidney transplant recipients with cancer. Given the complexities associated with the care of transplant patients, along with the advent of novel cancer therapies such as immune checkpoint inhibitors and chimeric antigen-receptor T cells, there is a dire need for the subspecialty of transplant onconephrology. The management of cancer in the setting of kidney transplantation is best accomplished by a multidisciplinary team, including transplant nephrologists, oncologists, and patients.

Scope and Consistency of Cancer Outcomes Reported in Randomized Trials in Kidney Transplant Recipients.

Introduction: Cancer is an important outcome in kidney transplantation, but the scope and consistency of how cancer is defined and reported in trials involving kidney transplant recipients has not been evaluated. This study aimed to assess the range and variability of cancer outcomes in trials involving kidney transplant recipients.

Methods: The ClinicalTrials.

Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell therapy.

Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers to successful organ transplantation. B cell-depleting treatments are used to reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the primary source for anti-HLA antibodies is long-lived plasma cells, which are ineffectively targeted by B cell depletion.

CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review.

Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown.

Epidemiology of Renal Cell Carcinoma: 2022 Update.

Context: International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate opportunities to reduce its incidence through prevention and surveillance.

Objective: To retrieve and summarize global incidence and mortality rates of KC and risk factors associated with its development, and to describe known familial syndromes and genetic alterations that represent biologic risk factors.

Immune Checkpoint Inhibitor Use in Solid Organ Transplant Recipients: A Systematic Review.

Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs.

The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients.

The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another.

Kidney recipients with allograft failure, transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers.

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers.

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020.

Changes in cancer incidence and outcomes among kidney transplant recipients in the United States over a thirty-year period.

Recipients of kidney transplants have elevated cancer risk compared with the general population. Improvements over time in transplant care and cancer treatment may have affected incidence and outcomes of cancer among recipients of kidney transplant. To evaluate this, we used linked United States transplant and cancer registry data to study 101,014 adult recipients of kidney transplants over three decades (1987-1996, 1997-2006, 2007-2016).

Contemporary patterns in kidney graft survival from donors after circulatory death in the United States.

Background: Kidney transplants from donors after circulatory death (DCD) make up an increasing proportion of all deceased donor kidney transplants in the United States (US). However, DCD grafts are considered to be of lower quality than kidneys from donors after brain death (DBD). It is unclear whether graft survival is different for these two types of donor kidneys.

Burden of excess mortality after implementation of the new kidney allocation system may be borne disproportionately by middle-aged recipients.

Under the new kidney allocation system (KAS), implemented in 2014, the distribution of the best quality donor kidney grafts shifted between age groups, but it is unclear whether this change translates to meaningful differences in post-transplant outcomes. We conducted a retrospective cohort study of 20,345 deceased donor kidney transplant recipients before and 4,605 recipients after implementation of the KAS using data from the United Network of Organ Sharing. Overall, two-year mortality was greater among recipients in the post-KAS era compared with the pre-KAS era (6.