Medical Director, Kidney Transplant Program
The Children's Hospital of Philadelphia
Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS): A Biomarker Cohort Study in Children
Sandra Amaral1, Brendan Keating2, Juhi Kumar3.
1Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States; 2Transplant Surgery, Univ of Pennsylvania, Philadelphia, PA, United States; 3Pediatrics, Weill-Cornell, New York, NY, United States
Introduction: Children with ESRD require multiple transplants over a lifetime, incurring repeated surgical and immunological risks with each newly transplanted organ. Allograft injury occurs primarily due to acute cellular rejection (ACR) and/or antibody mediated rejection (AMR) and viral infections, such as BK virus associated nephropathy (BKVN). A major hindrance to promoting long-term allograft survival is the lack of non-invasive diagnostic and prognostic biomarkers to reliably detect early allograft injury before clinical manifestations arise.
Methods: The VIRTUUS study is a NIH-sponsored, multi-center prospective cohort study of pediatric kidney transplant recipients across the United States and Canada. The study aims to examine whether or not previously validated urinary cell messenger RNA (mRNA) and metabolite profiles in adult kidney transplant recipients are diagnostic and prognostic of ACR and BKVN in pediatric kidney transplant recipients. Specifically, we will investigate whether the adult urinary cell mRNA 3-gene signature composed of 18S-normalized CD3ε, CXCL10 mRNA and 18S rRNA is able to discriminate allograft biopsies with ACR from biopsies without rejection. We will examine trajectories of these mRNA signatures to evaluate whether they can predict ACR before biopsy-confirmed ACR and changes in serum creatinine. We will also examine whether a combined metabolite profile and urinary cell mRNA 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR. Lastly, we will investigate whether levels of BKV VP-1 mRNA in urinary cells are diagnostic of BKVN, and whether urinary cell levels of plasminogen activator inhibitor-1 (PAI-1) mRNA predict allograft failure.
Results: We began recruitment in 2017 and anticipate recruiting 450 incident subjects < 18 years of age who receive a kidney transplant between 2017 and 2020. We are collecting urine samples prospectively at multiple time points during the first post-transplant year and at times of allograft biopsies done for surveillance or indication. To date, we have created a REDCap database to support data collection and research coordinators have been trained on data entry. Lab technicians have received training on urine processing and shipping to support study fidelity and feasibility with webinars and videos available to provide ongoing education to staff.
Conclusions: If these validated adult noninvasive diagnostic and prognostic urine biomarkers of kidney allografts characterize early kidney allograft injury in pediatric recipients, our study will create opportunities for non-invasive immune surveillance to inform preemptive treatment decisions before clinical signs arise, resulting in better long-term allograft outcomes.
11:15 - 11:45
|Back to Basics: Talking Instead of Texting||Peer mentoring<span uk-icon="video-camera"></span>||Stanley Park - Ballroom 1|
11:45 - 12:30
|Social Media: Friend or Foe||Debaters<span uk-icon="video-camera"></span>||Stanley Park - Ballroom 1|
10:00 - 11:00
|Novel Methods for Post-Transplant Surveillance||Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS): A Biomarker Cohort Study in Children <span uk-icon="video-camera"></span>||Bayshore D|
08:00 - 09:30
|Clinical Experiences in Renal Transplantation||U-REAACT: Using mobile health to promote medication adherence in youth with kidney transplants<span uk-icon="video-camera"></span>||Bayshore D|