Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices.

Introduction: The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short-term graft survival. However, improvements in longer-term outcomes have been much less apparent.

Clinical conundrums in pediatric kidney transplantation: What we know about the role of angiotensin II type I receptor antibodies in pediatric kidney transplantation and the path forward.

Antibodies to angiotensin II type 1 receptor (AT1R-Abs) are among the most well-studied non-HLA antibodies in renal transplantation. These antibodies have been shown to be common in pediatric kidney transplantation and associated with antibody-mediated rejection (AMR), vascular inflammation, development of human leukocyte donor-specific antibodies (HLA DSA), and allograft loss. As AT1R-Ab testing becomes more readily accessible, evidence to guide clinical practice for testing and treating AT1R-Ab positivity in pediatric kidney transplant recipients remains limited.

Non-HLA Antibodies to G Protein-coupled Receptors in Pediatric Kidney Transplant Recipients: Short- and Long-term Clinical Outcomes.

Background: Angiotensin II type 1 receptor antibodies (AT1R-Abs) and endothelin-type A receptor antibodies (ETAR-Abs) are G protein-coupled receptor activating autoantibodies associated with antibody-mediated rejection, vascular pathology, increased cytokines, allograft dysfunction, and allograft loss in pediatric kidney transplant recipients in the first 2 y posttransplantation. The impact of AT1R-Ab and ETAR-Ab positivity on longer-term 5-y transplant outcomes is unknown.

Methods: One hundred pediatric kidney transplant recipients were tested for ETAR-Ab and AT1R-Ab on serially collected blood samples in the first 2 y posttransplant.

Validation of a prediction system for risk of kidney allograft failure in pediatric kidney transplant recipients: An international observational study.

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included.

Angiotensin II type 1 receptor antibodies and native kidney function in pediatric liver and intestinal transplant recipients.

Background: Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored.

Methods: Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period.

Envarsus XR® pharmacokinetics in adolescents post-kidney transplantation - A pilot study.

Introduction: Envarsus XR® (LCPT), a once daily dosage formulation of tacrolimus, is an FDA-approved medication in adult renal transplant recipients (RTRs). There are limited data on its pharmacokinetics (PK) in adolescent RTRs. We report here the PK profile of LCPT in adolescent RTRs.

Deceased donor organ allocation in pediatric transplantation: A historical narrative.

Background: Since the earliest clinical successes in solid organ transplantation, the proper method of organ allocation for children has been a contentious subject. Over the past 30-35 years, the medical and social establishments of various countries have favored some degree of preference for children on the respective waiting lists. However, the specific policies to accomplish this have varied widely and changed frequently between organ type and country.

Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.

Background: Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression.

Methods: We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab.

De novo lupus-like glomerulonephritis after pediatric non-kidney organ transplantation.

Background: We propose a novel clinically significant finding, de novo lupus-like glomerulonephritis (DNLLGN), in patients with autoantibodies and kidney abnormalities in pediatric liver transplant (LT) and intestinal inclusive transplants (ITx).

Methods: We describe the clinical, serologic, and histopathologic presentation and kidney outcomes in eight patients from our center found to have DNLLGN on kidney biopsy.

Results: Pediatric recipients of non-kidney solid organ transplants developed an unusual de novo immune complex glomerulonephritis with morphologic similarity to lupus nephritis.

Associations among erythropoietic, iron-related, and FGF23 parameters in pediatric kidney transplant recipients.

Background: In pediatric kidney transplant recipients, anemia is common and oftentimes multifactorial. Hemoglobin concentrations may be affected by traditional factors, such as kidney function and iron status, as well as novel parameters, such as fibroblast growth factor 23 (FGF23).

Methods: Here, we evaluated associations among erythropoietic, iron-related, and FGF23 parameters in a cohort of pediatric kidney transplant recipients, hypothesizing that multiple factors are associated with hemoglobin concentrations.

Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections).

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation.

Introduction: Autoantibody to angiotensin II type 1 receptor (AT1R-Ab) has been recognized as a non-human leukocyte antigen (HLA) antibody relevant in transplantation. Endothelin type A receptor antibody (ETAR-Ab) has been strongly associated with AT1R-Ab, but the data in kidney transplantation are scarce.

Methods: We examined the relationship of ETAR-Ab and AT1R-Ab with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibody (DSA) in a cohort of pediatric renal transplant recipients.

AT1R Activating Autoantibodies in Hematopoietic Stem Cell Transplantation.

Angiotensin II type 1 receptor activating autoantibodies (AT1R-AAs) have gained attention in solid organ transplant as non-HLA antibodies associated with rejection, vasculopathy, and graft dysfunction. These antibodies have also been reported in the context of pre-eclampsia, scleroderma, and isolated hypertension. Here, we present 3 post-hematopoietic stem cell transplant (HSCT) cases with patients demonstrating elevated levels of AT1R-AAs detected within the first year post-HSCT.

Establishing core outcome domains in pediatric kidney disease: report of the Standardized Outcomes in Nephrology-Children and Adolescents (SONG-KIDS) consensus workshops.

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology-Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals).

The Improving Renal Outcomes Collaborative: Blood Pressure Measurement in Transplant Recipients.

Background And Objectives: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients.

Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies.

Introduction: Angiotensin II type 1 receptor antibody (AT1R-Ab), is a non-human leukocyte antigen (HLA) antibody implicated in poor renal allograft outcomes, although its actions may be mediated through a different pathway than HLA donor-specific antibodies (DSAs). Our aim was to examine serum cytokine profiles associated with AT1R-Ab and distinguish them from those associated with HLA DSA in serially collected blood samples from a cohort of pediatric renal transplant recipients.

Methods: Blood samples from 65 pediatric renal transplant recipients drawn during the first 3 months posttransplant, at 6, 12, and 24 months posttransplant, and during suspected episodes of kidney transplant rejection were tested for AT1R-Ab, HLA DSA, and a panel of 6 cytokines (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-8, IL-1β, IL-6, and IL-17).

Angiotensin II type I receptor antibodies in pediatric solid organ transplant.

Minimizing immunologic complications is critical for long-term patient survival in pediatric solid organ transplant recipients. Multiple factors distinguish pediatric from adult organ transplant recipients which may influence the risk and manifestations of immunologic responses. Angiotensin II type 1 receptor antibody (AT1R-Ab) is a non-HLA antibody that has been has been associated with poor clinical outcomes in adult kidney transplant recipients.

Angiotensin II Type 1 receptor antibodies are associated with inflammatory cytokines and poor clinical outcomes in pediatric kidney transplantation.

Angiotensin II type 1 receptor (AT1R) antibody has been linked to poor allograft outcomes in adult kidney transplantation. However, its clinical consequences in children are unknown. To study this, we examined the relationship of AT1R antibody with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibodies (DSA) in a cohort of pediatric renal transplant recipients.

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection.

Background: Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients.

Methods: We examined seven patients with treatment-refractory C4d + AMR.

The Clinical Impact of Non-HLA Antibodies in Solid Organ Transplantation.

Antibody-mediated rejection in solid organ transplantation is associated with significant organ dysfunction and allograft loss. Donor-specific antibodies against human leukocyte antigens (HLAs) have been a major focus for research, clinical testing, and therapies. Recently, non-HLA autoantibodies to various endothelial antigens including angiotensin II type 1 receptor, endothelin-1 type A receptor, Major Histocompatibility Complex Class 1-Related Chain A, perlecan, and collagen V are emerging as both potential mediators of allograft dysfunction and targets for intervention.

Accelerated rejection, thrombosis, and graft failure with angiotensin II type 1 receptor antibodies.

Background: Angiotensin II type 1 receptor antibodies (AT1R-Abs) have been implicated in renal transplant rejection and failure; however, the mechanism of allograft damage, patterns of clinical presentation, and response to desensitization of AT1R-Abs have not been clearly established.

Case Diagnosis/treatment: We present the case of a 7-year-old boy with preformed AT1R-Abs who developed accelerated vascular and cellular rejection and renal allograft thrombosis despite desensitization and treatment with angiotensin receptor blockade. Although an association between AT1R-Abs and microvascular occlusion has been previously described, we are the first to describe an association between AT1R-Abs and renal artery thrombosis, leading to devastating early allograft failure.

Loss of p16INK4A expression in low-grade ovarian serous carcinomas.

According to a tumor progression model, low-grade ovarian serous carcinomas may evolve from serous borderline tumors or micropapillary tumors. We sought to investigate the role of and associations between BRAF mutational status, extracellular signal regulated kinase activation, and p16(INK4A) expression in various types of ovarian serous tumors. We analyzed 29 typical ovarian serous borderline tumors, 8 micropapillary tumors, 4 low-grade invasive ovarian serous carcinomas, and 24 high-grade invasive ovarian serous carcinomas for the BRAF mutational status at codon 600; in addition, expression levels of the downstream signaling protein extracellular signal regulated kinase and the p16(INK4A) tumor suppressor protein were assessed by immunohistochemistry.

Childhood obesity and the built environment.

Purpose Of Review: Neighborhood factors are increasingly examined for their role in the childhood obesity epidemic. Whereas studies on the impacts of neighborhood factors on adult obesity are relatively common, studies examining these same factors on childhood obesity are far fewer.

Recent Findings: Using the Ecological Systems Theory (EST) as a model, we sought to examine the strength of the literature with respect to neighborhood factors as outlined in EST.