IPTA Newsletter - September 2018


The IPTA Nominations Committee is seeking qualified candidates to be considered for open Councilor and Officer positions beginning in May 2019.

All applications will be reviewed by the IPTA Nominations Committee, who will present a final slate of candidate Officers and Councilors to the IPTA membership for the 2019 election.

The IPTA Nominations Committee welcomes nominations and applications from anyone who has been an IPTA member in good standing for at least 1 year. Service to IPTA on committees or special activities relevant to the society is an asset.

The deadline for online submission of applications is September 30th, 2018.

10th Congress of the International Pediatric Transplant Association

The planning of the 10th Congress is well underway and we are thrilled with the list of speakers that have confirmed their participation! The Plenary and SOTA speakers are listed in the online preliminary program at ipta2019.org. International collaboration is an important part of the IPTA 2019 Congress. We have actively pursued opportunities to partner with other transplant and pediatric organizations across the world. It is important that we all work together as a community to advance the science and practice of pediatric transplantation. The Vancouver Congress will showcase collaborative sessions between IPTA and the following organizations: European Society for Organ Transplantation (ESOT); American Association for the Study of Liver Diseases (AASLD); American Society for Histocompatibility & Immunogenetics (ASHI); the International Society for Heart and lung Transplantation (ISHLT); American Society of Transplantation (AST); The Transplantation Society - International CMV Consensus Group; American Society of Pediatric Nephrology (ASPN); Canadian Blood Services (CBS); American Society of Transplant Surgeons (ASTS), and more to come.

This newsletter’s literary highlights come from David M. Briscoe, MD. MRCP. Director, Transplant Research Program, Boston Children's Hospital and the Department of Pediatrics, Harvard Medical School, Boston MA.

  1. Seifert ME et al. Subclinical inflammation phenotypes and long-term outcomes after pediatric kidney transplantation. Am J Transplant 2018; 1-11 [PMID: 29766640]

    Despite improvements in short-term graft survival, long term outcomes following renal transplantation have not changed in over 20 years. One possibility is that standard clinical tests (e.g. creatinine and eGFR) only enable the diagnosis of intragraft disease once inflammation and fibrosis are present, which is more resistant to treatment. This is particularly relevant for pediatric kidney transplant recipients in whom creatinine-based eGFR is most imprecise because of the size mismatch between the child and the adult-sized kidney allograft. In this study, Seifert et al reported on the use of surveillance biopsies performed at 3 and/or 6 months post-transplant in a cohort of 120 pediatric recipients as a tool to identify subclinical inflammation (i.e. not detected using serum creatinine measurements). They also evaluated both the prevalence of pathological phenotypes seen on each biopsy and whether the use of surveillance had an impact on 5-year outcomes. This study represents one of the largest pediatric studies on surveillance biopsies to date. The major findings were: 1), that subclinical inflammation, either borderline or acute T cell-mediated rejection, was detectable in 36% of recipients by 6 months post transplant; 2), that the presence of subclinical inflammation in a surveillance biopsy is associated with increased risk for graft failure by year 5 post transplant; and 3), that treating subclinical rejection results in a better long-term outcome. They conclude that subclinical/borderline rejection is prevalent in pediatric recipients, that surveillance biopsies are safe and that intervention therapy has high potential to improve long-term outcomes. These findings also highlight the great need to monitor pediatric recipients with precision tools such as biomarker assays that support either the identity of high-risk patients or those recipients who are truly stable. It is also possible that precision biomarker assays may serve as a tool to identify pediatric recipients in need of surveillance biopsy.

  2. Faddoul G et al. Analysis of Biomarkers Within the Initial 2 Years Posttransplant and 5-Year Kidney Transplant Outcomes: Results From Clinical Trials in Organ Transplantation-17. Transplantation 2018 Apr;102(4):673-680 [PMID: 29189482]

    Several studies have demonstrated that increases in levels of the chemokines CXCL9 or CXCL10 in urine have a >70% sensitivity and specificity for association with intragraft inflammation/rejection. Their use as biomarkers has advantages to identify both low-risk stable patients as well as those at risk of graft failure. One of the larger studies evaluating urine biomarkers in the US enrolled 280 adult first kidney transplants as part of the NIH-sponsored Clinical Trials in Organ Transplantation (CTOT). This study revealed that urinary CXCL9 and/or other gene expression levels and assays including IFNy ELISPOT are excellent for detecting rejection. In the current study, Faddoul et al and the CTOT consortium reported the results of a follow up analysis of 5-year outcome data. Their analyses showed that early biomarker assays (within the first 2 years), including urinary CXCL9 levels, do not associate with long-term outcomes. In contrast, in this adult cohort they find that eGFR decline in the posttransplant period from 6 months to 2 years is a better surrogate of graft loss at 5 years. While this study highlights the utility of urine chemokine assays as biomarkers of rejection, it did not include pediatric recipients, in whom creatinine levels and eGFR are somewhat imprecise measures of early intragraft disease.

  3. Mincham CM et al. Evolution of renal function and urinary biomarker indicators of inflammation on serial kidney biopsies in pediatric kidney transplant recipients with and without rejection. Pediatr Transplant 2018 Aug;22(5):e13202. doi: 10.1111/petr.13202. Epub 2018 Apr 25. [PMID: 29696778]

    There is a great need to improve our ability to detect of subtle inflammation and subclinical rejection in pediatric renal transplant recipients. As discussed above (see Seifert et al), the use of surveillance biopsies can detect disease in over one-third of so-called ‘stable’ patients as assessed using standard creatinine-based clinical testing. This observation should serve as an added stimulus to advance the use of precision biomarkers in pediatric patients who are at risk of late diagnosis using current clinical assessment tools. To date, the search for reliable, sensitive and specific biomarkers has shown that the measurement of CXCL9 and CXCL10 in urine has high potential for utility as an early biomarker of intragraft disease. In this study, Mincham et al evaluated urinary CXCL10 levels in pediatric recipients as a follow up study from their group to evaluate longitudinal performance in the assessment of response to treatment. In this cohort, assays were performed at the same time as two consecutive renal biopsies, and urinary biomarker levels were correlated with pathology in a total of 49 biopsy pairs. Biopsy #1 was performed at a median of 11.7 months post-transplant and biopsy #2 was obtained 1.8 ± 0.8 months later. In their analysis the authors evaluated urinary CXCL10 levels as a ratio with urinary creatinine in order to enhance sensitivity. They also evaluated data on 134 unique metabolites according to a model previously reported by their group. Their major findings were: 1), that urine levels of CXCL10:Cr increase in association with rejection; 2), that levels decline ( P=0.01) following effective treatment of rejection; and 3), that low biomarker levels are present in patients without rejection. They also found that the metabolic measurements change directly in association with the degree of histological acuity on each biopsy. They conclude that urinary biomarkers associate with biopsy evidence of rejection in pediatric recipients, and that urinary levels of CXCL10:Cr are superior to serum creatinine as an index of histological disease.

Summary: Collectively, these three studies add strong support for the use of urinary biomarker assays as a precision tool in pediatric renal transplant recipients to identify: a), stable patients, b) patients in whom a surveillance biopsy is indicated, and c), to follow up the efficacy of an intervention treatment. Clinical trials are needed to further validate these possibilities and determine if the routine use of urinary biomarkers will advance care and outcomes in pediatric patients.

2019 IPTA Congress Awards

Nominations will open for the IPTA 2019 Awards on October 8. The selected candidates will be presented with their awards at the 2019 IPTA 10th Congress on Pediatric Transplantation.

IPTA Members are encouraged to nominate a colleague for any of the three awards being offered:

Purpose: To recognize a member who has made outstanding contributions to the field of pediatric transplantation over the course of their career.

Purpose:To recognize junior investigators who show scholarly promise, encourage them in their careers in pediatric transplantation and provide assistance to attend the IPTA Scientific Congress.

Purpose:To recognize an Allied Health Professional member who has rendered years of faithful service to the Society and/or who has made a significant contribution to pediatric transplantation.

Outreach Committee Update

Outreach Program Renewal and Launch: The IPTA is pleased to announce the renewal of its Outreach Program, established to support centers that seek to develop new solid organ transplant programs or to expand or enhance the quality of care in existing programs. The success of the Outreach Programs is enabled by enthusiastic participation of sponsoring programs, who will partner with applicant centers and can provide knowledge, expertise and education. Details regarding the Outreach Program guidelines and application process can be found HERE

Transplant Program Standards Development: In order to better understand requirements for establishing and supporting successful transplant programs, the IPTA Outreach Committee has developed a set of simple standards that may be used to evaluate transplant program needs. These standards are meant to support the development of best practices in centers seeking support by the IPTA Outreach Program, but may also serve as a reference for programs seeking their own program development. They are meant to be adaptable to the specific circumstances of transplant centers around the world. These standards are being launched in association with the Outreach Program Renewal, and are available for reference on the IPTA website. We anticipate that these standards will need to be further refined and the Outreach Committee is looking forward to active feedback and is committed to updating the standards with input from the IPTA member community.

On behalf of the IPTA Outreach Committee
Tom D. Blydt-Hansen, MDCM, FRCPC
Associate Professor of Pediatrics, University of British Columbia
Director, Multi-Organ Transplant Program, BC Children’s Hospital

Dear IPTA Colleagues,

The overarching goal of the Peer Mentoring initiative is to facilitate and improve the quality of publications being sent by our membership to transplant journals, especially Pediatric Transplantation. One means of achieving this goal is to assist our membership, especially junior faculty and faculty from emerging transplant communities, in manuscript preparation. This will allow for these members to have dialogue with those experienced in the publication process prior to final submission.

We are seeking interested individuals who would be willing to help out with this new initiative. Responsibilities would include providing reviewer style feedback to the mentee prior to manuscript submission, and being available for subsequent questions. All members, including non-physician members, are encouraged to participate.

If interested, please send your name, email, and any specific areas of research focus to peermentor@iptaonline.org.

Thank you in advance for your support,

Peer Mentoring Workgroup, IPTA
Chesney Castleberry, Workgroup Leader

Newsletter Announcements – Open to the Membership

Would you like to include an event announcement in the newsletter? Some potential examples of this may include:

  1. Event/meeting announcements
  2. Job opportunities/postings
  3. Requests for colleagues to join multi-center research collaborations

If you have any of these that you wish to include in the newsletter, please email to mary.smith@tts.org. Please note that in any announcement about events or job opportunities, no follow-up will be provided by IPTA – as such, full contact information for all of these events/opportunities should be included in the announcement. Please try to keep these relevant to the field of pediatric transplantation and pediatric organ failure.



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