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

2021

e791

2021 Dec

2373-8731

<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>

10.1097/TXD.0000000000001244

Transplant Direct

34805493

Early Detection of SARS-CoV-2 and other Infections in Solid Organ Transplant Recipients and Household Members using Wearable Devices.

2021

2021 Mar 18

1432-2277

<p>The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns and blood oxygen saturation, show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in &gt;80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2 and other infections are also reviewed.</p>

10.1111/tri.13860

Transpl Int

33735480