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

Race and Ethnicity Predict Bone Markers and Fracture in Pediatric Patients With Chronic Kidney Disease.

2021

298-304

2021 02

1523-4681

<p>Studies in healthy children have shown racial-ethnic differences in bone markers and bone outcomes including fractures. At present, limited studies have evaluated the impact of race and ethnicity on bone markers and fractures within the pediatric chronic kidney disease (CKD) population. In a cohort study of 762 children between the ages of 1.5 years and 18 years, with CKD stages 1 to 4 from the CKD in children (CKiD) cohort, the relationship between racial-ethnic group and bone markers (parathyroid hormone [PTH], 25-hydroxyvitamin D [25-OHD], 1,25-dihydroxyvitamin D [1,25(OH) D], and C-terminal fibroblast growth factor [FGF23]) was determined using linear mixed models. Additionally, logistic regression was used to evaluate racial-ethnic differences in prevalent fracture upon study entry. Black race was associated with 23% higher PTH levels (confidence interval [CI], 2.5% to 47.7%; p = .03), 33.1% lower 25-OHD levels (CI, -39.7% to -25.7%; p &lt; .0001), and no difference in C-terminal FGF23 or 1,25(OH) D levels when compared to whites. Hispanic ethnicity was associated with 15.9% lower C-terminal FGF23 levels (CI, -28.3% to -1.5%; p = .03) and 13.8% lower 25-OHD levels (CI, -22.2% to -4.5%; p = .005) when compared to whites. Black and Hispanic children had 74% (odds ratio [OR] 0.26; CI, 0.14 to 0.49; p = .001) and 66% (OR 0.34; CI, 0.17 to 0.65; p &lt; .0001) lower odds of any fracture than white children at study entry, respectively. Race and ethnicity are associated with differences in bone markers and despite lower 25-OHD levels, both black and Hispanic children with CKD reported a lower prevalent fracture history than white children. The current findings in the CKD population are similar to racial-ethnic differences described in healthy children. Additional studies are needed to better understand how these differences might impact the management of pediatric CKD-MBD. © 2020 American Society for Bone and Mineral Research (ASBMR).</p>

10.1002/jbmr.4182

J Bone Miner Res

32960469

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

Association Between Chronic Kidney Disease-Mineral Bone Disease (CKD-MBD) and Cognition in Children: Chronic Kidney Disease in Children (CKiD) Study.

2020

398-406

2020 Jul-Aug

2590-0595

<p><strong>Rationale &amp; Objective: </strong>Chronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.</p>

<p><strong>Study Design: </strong>Observational study.</p>

<p><strong>Participants: </strong>702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.</p>

<p><strong>Predictors: </strong>Plasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]D).</p>

<p><strong>Outcomes: </strong>Neurocognitive tests of intelligence, academic achievement, and executive functions.</p>

<p><strong>Analytical Approach: </strong>Linear regression models to analyze the cross-sectional associations between logFGF-23, 25(OH)D, 1,25(OH)D, PTH, calcium, and phosphorus scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.</p>

<p><strong>Results: </strong>At baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73&nbsp;m. In fully adjusted analyses, 25(OH)D, 1,25(OH)D, PTH, calcium, and phosphorus scores did not associate with cognitive test scores. In fully adjusted analyses, logFGF-23 was associated with abnormal test scores for attention regulation (&nbsp;&lt;&nbsp;0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (β&nbsp;=&nbsp;2.3&nbsp;[1.0, 3.6]), Variability (β=1.4 [0.4,&nbsp;-2.4]), and Hit Reaction Time (β&nbsp;=&nbsp;1.3&nbsp;[0.2, 2.4]). Children in the highest FGF-23 tertile group had 7% and 9% greater cognitive risk for&nbsp;Hit Reaction Time and Errors of Omission compared with those in the lowest tertile, respectively. In fully adjusted analyses, higher FGF-23 tertile was associated with increased cognitive risk (&nbsp;&lt;&nbsp;0.05) for Errors of Omission (β&nbsp;=&nbsp;0.4&nbsp;[0.1,&nbsp;0.7]) and Hit Reaction Time (β&nbsp;=&nbsp;0.4&nbsp;[0.1, 0.7]).</p>

<p><strong>Limitations: </strong>The study does not assess the cumulative&nbsp;effects of FGF-23 excess on cognitive function over time. Within-population stratified analyses were not performed due to limited sample size.</p>

<p><strong>Conclusions: </strong>In children with CKD, higher plasma FGF-23 level is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of glomerular filtration rate.</p>

10.1016/j.xkme.2020.03.005

Kidney Med

32775979