First name
Asha
Last name
Moudgil

Title

Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

Year of Publication

2021

Number of Pages

e791

Date Published

2021 Dec

ISSN Number

2373-8731

Abstract

<p>Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients.</p>

<p><strong>Methods: </strong>Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (-normalized mRNA, and ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure.</p>

<p><strong>Results: </strong>To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted.</p>

<p><strong>Conclusions: </strong>Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.</p>

DOI

10.1097/TXD.0000000000001244

Alternate Title

Transplant Direct

PMID

34805493

Title

Developing a framework for evaluating kidney transplantation candidacy in children with multiple comorbidities.

Year of Publication

2015

Number of Pages

5-13

Date Published

2015 Jan

ISSN Number

1432-198X

Abstract

<p>Children with multiple comorbidities, including neurodevelopmental delay, can develop end-stage kidney disease (ESKD). When and if these children should be eligible for kidney transplantation is an area of debate within the pediatric nephrology community and the public. Discussions focus on expected survival and quality of life posttransplant, as well as resource allocation decisions, as donor kidneys remain a limited resource. This paper focuses on the evidence available regarding outcomes in this population and the ethical issues that should be considered. The authors offer a framework for transplant teams evaluating children with comorbidities for kidney transplant, focusing on the benefits and burdens that transplantation can be expected to achieve.</p>

DOI

10.1007/s00467-013-2704-4

Alternate Title

Pediatr. Nephrol.

PMID

24452328

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