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

A Randomized Trial of a Multicomponent Intervention to Promote Medication Adherence: The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).

2018

2018 Mar 15

1523-6838

<p><strong>BACKGROUND: </strong>Poor adherence to immunosuppressive medications is a major cause of premature graft loss among children and young adults. Multicomponent interventions have shown promise but have not been fully evaluated.</p>

<p><strong>STUDY DESIGN: </strong>Unblinded parallel-arm randomized trial to assess the efficacy of a clinic-based adherence-promoting intervention.</p>

<p><strong>SETTING &amp; PARTICIPANTS: </strong>Prevalent kidney transplant recipients 11 to 24 years of age and 3 or more months posttransplantation at 8 kidney transplantation centers in Canada and the United States (February 2012 to May 2016) were included.</p>

<p><strong>INTERVENTION: </strong>Adherence was electronically monitored in all participants during a 3-month run-in, followed by a 12-month intervention. Participants assigned to the TAKE-IT intervention could choose to receive text message, e-mail, and/or visual cue dose reminders and met with a coach at 3-month intervals when adherence data from the prior 3 months were reviewed with the participant. "Action-Focused Problem Solving" was used to address adherence barriers selected as important by the participant. Participants assigned to the control group met with coaches at 3-month intervals but received no feedback about adherence data.</p>

<p><strong>OUTCOMES: </strong>The primary outcomes were electronically measured "taking" adherence (the proportion of prescribed doses of immunosuppressive medications taken) and "timing" adherence (the proportion of doses of immunosuppressive medications taken between 1 hour before and 2 hours after the prescribed time of administration) on each day of observation. Secondary outcomes included the standard deviation of tacrolimus trough concentrations, self-reported adherence, acute rejection, and graft failure.</p>

<p><strong>RESULTS: </strong>81 patients were assigned to intervention (median age, 15.5 years; 57% male) and 88 to the control group (median age, 15.8 years; 61% male). Electronic adherence data were available for 64 intervention and 74 control participants. Participants in the intervention group had significantly greater odds of taking prescribed medications (OR, 1.66; 95% CI, 1.15-2.39) and taking medications at or near the prescribed time (OR, 1.74; 95% CI, 1.21-2.50) than controls.</p>

<p><strong>LIMITATIONS: </strong>Lack of electronic adherence data for some participants may have introduced bias. There was low statistical power for clinical outcomes.</p>

<p><strong>CONCLUSIONS: </strong>The multicomponent TAKE-IT intervention resulted in significantly better medication adherence than the control condition. Better medication adherence may result in improved graft outcomes, but this will need to be demonstrated in larger studies.</p>

<p><strong>TRIAL REGISTRATION: </strong>Registered at ClinicalTrials.gov with study number NCT01356277.</p>

10.1053/j.ajkd.2017.12.012

29602631

Outcomes Among Children Who Received a Kidney Transplant in the United States From a Hepatitis B Core Antibody-Positive Donor, 1995-2010.

2015

2015 Oct 14

2048-7207

<p><strong>BACKGROUND: </strong>Accepting kidneys for transplant from donors with a history of hepatitis B virus infection may increase the availability of organs for those with end-stage kidney disease. In adult recipients, kidney transplants from hepatitis B virus core antibody-positive donors have resulted in favorable graft and patient survival rates. However, pediatric organ transplant recipients have developing immune systems and a higher risk of infectious complications than adults. Accordingly, little is known about the outcomes of children who have received a kidney transplant from a hepatitis B virus core antibody-positive donor.</p>

<p><strong>METHODS: </strong>We included 11 898 children ≤18 years of age who received a first kidney transplant in the United States between January 1, 1995, and December 31, 2010, and who were recorded in the Scientific Registry of Transplant Recipients. We examined differences in graft and patient survival rates among children who received a kidney transplant from a hepatitis B virus core antibody-positive donor.</p>

<p><strong>RESULTS: </strong>There were 199 children (1.7%) who received a kidney transplant from a hepatitis B virus core antibody-positive donor. More than 80% of these transplants occurred in recipients who were hepatitis B virus core antibody and surface antigen negative. After a median follow-up of 7.9 years, there were no significant differences in the adjusted graft (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.80-1.31]) or patient (HR, 1.12 [95% CI, 0.73-1.73]) survival rates according to donor core antibody status.</p>

<p><strong>CONCLUSIONS: </strong>It may be acceptable, on a case-by-case basis, to consider hepatitis B virus core antibody-positive donors for kidney transplants to seroprotected children with end-stage kidney disease.</p>

10.1093/jpids/piv070

J Pediatric Infect Dis Soc

26501473