First name
Juhi
Last name
Kumar

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

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

Year of Publication

2021

Number of Pages

298-304

Date Published

2021 02

ISSN Number

1523-4681

Abstract

<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>

DOI

10.1002/jbmr.4182

Alternate Title

J Bone Miner Res

PMID

32960469

Title

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

Year of Publication

2021

Date Published

2021 Mar 18

ISSN Number

1432-2277

Abstract

<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>

DOI

10.1111/tri.13860

Alternate Title

Transpl Int

PMID

33735480

Title

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

Year of Publication

2020

Number of Pages

398-406

Date Published

2020 Jul-Aug

ISSN Number

2590-0595

Abstract

<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>

DOI

10.1016/j.xkme.2020.03.005

Alternate Title

Kidney Med

PMID

32775979

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