Publications by authors named "Charles Varnell"

Objective: Assessing barriers to adherence provides helpful information to clinicians. The objective of this study was to describe the clinical utility of the Barriers Assessment Tool (BAT) using clinical data for a large, midwestern U.S.

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Background: Abnormal serum magnesium (Mg) concentrations are common and associated with worse mortality in kidney-transplant recipients. Many kidney and transplant-related factors affect Mg homeostasis. The concentration of the active form, ionized Mg (iMg), is not measured clinically, and total Mg (tMg) and iMg correlations have conflicted.

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Article Synopsis
  • Tacrolimus is the main immunosuppressant used in kidney transplants, requiring careful monitoring of drug levels due to its narrow therapeutic range and metabolism by specific genes (CYP3A4/5).
  • A study of 93 patients under 21 showed that those with intermediate or normal metabolizer status (CYP3A5 IM/NM) took longer to reach the desired drug levels and required more dose adjustments compared to poor metabolizers (PM).
  • The findings suggest that preemptive genetic testing for CYP3A5 variants could help personalize dosing, reduce adjustments, and optimize treatment for transplant patients.
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Background: To date, the evidence for proteasome-inhibitor (PI) based antibody mediated rejection (AMR) therapy has been with the first-generation PI bortezomib. Results have demonstrated encouraging efficacy for early AMR with lesser efficacy for late AMR. Unfortunately, bortezomib is associated with dose-limiting adverse effects in some patients.

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The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care.

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Background: We report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).

Methods: Patient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.

Results: From September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients.

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Learning health systems (LHS) align science, informatics, incentives, and culture for continuous improvement and innovation. In this organizational system, best practices are seamlessly embedded in the delivery process, and new knowledge is captured as an integral byproduct of the care delivery experience aimed to transform clinical practice and improve patient outcomes. The objective of this review is to describe how building better health systems that integrate clinical care, improvement, and research as part of an LHS can improve care within pediatric nephrology.

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Rationale & Objective: Nonadherence to medical regimens increases the risk of graft loss among adolescent and young adult recipients of kidney transplants. Interventions that improve adherence may decrease rejection rates, but their perceived costs are a barrier to clinical implementation. We developed a model to assess the cost-effectiveness of an adherence promotion strategy, the Medication Adherence Promotion System (MAPS).

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Rationale & Objective: Adolescent and young adult kidney transplant recipients have a high risk of rejection related to suboptimal adherence. Multicomponent interventions improve adherence in controlled trials, but clinical implementation is lacking. We describe an initiative to reduce allograft rejection using evidence-based adherence promotion strategies.

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Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss.

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Objective: Hypervitaminosis A is well-described but overlooked in chronic kidney disease (CKD) and has been associated with hypercalcemia, contributing to mineral bone disease. Our objective is to assess prevalence of hypervitaminosis A and its association with bone health in an advanced-CKD population.

Methods: We performed a retrospective review of 58 children with CKD 4-5 to examine the association between vitamin A levels and bone health and compared these values between a primarily formula-fed (FF) and nonprimarily formula-fed cohort (NFF).

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Background: Nonadherence to immunosuppression is common among pediatric, adolescent, and young adult kidney transplant recipients and a leading cause of graft loss. Assessing barriers to medication adherence in clinical practice may identify patients at risk for rejection and provide therapeutic targets.

Methods: Kidney transplant patients and/or their caregivers were assessed for 14 barriers to medication adherence using the barriers assessment tool.

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Article Synopsis
  • A study evaluated the impact of COVID-19 on children with kidney transplants by collecting clinical data from 22 centers and 281 tested patients.
  • 24 patients (8.5%) tested positive, with 63% showing symptoms; most were treated as outpatients, and serious complications were absent.
  • The overall incidence of COVID-19 in pediatric kidney transplant patients was low, estimated at 0.6%, indicating favorable short-term outcomes for this group.
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Background And Objectives: Kidney biopsy is an essential tool for the diagnosis and treatment of patients with kidney disease; however, because of its invasive nature, bleeding complications may arise.

Design, Setting, Participants, & Measurements: We performed a meta-analysis of prospective or retrospective observational studies and randomized, controlled trials in pediatric patients undergoing native or transplant kidney biopsy in an inpatient or outpatient setting in MEDLINE-indexed studies from January 1998 to November 1, 2017 to determine the proportion of patients who develop hematoma, need blood transfusion, or need an additional intervention due to a complication after kidney biopsy.

Results: Twenty-three studies of 5504 biopsies met inclusion criteria.

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Pediatric kidney transplant recipients must follow a complicated regimen of timely adherence to immunosuppressant medication, routine blood work, and medical follow-up visits. Failure to adhere to the recommended regimen can result in medical complications and costly treatment. We developed a novel risk score to identify patients at risk for poor adherence behaviors and evaluated whether it would predict future health care utilization and charges.

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MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls.

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Patient-identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post-transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient-centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non-judgmental discussion around adherence.

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Primary cilia sense environmental conditions, including osmolality, but whether cilia participate in the osmotic response in renal epithelial cells is not known. The transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known.

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Our study was developed to ascertain reference ranges of 11-dehydrothromboxane B2 (11-dhTXB2) in the urine of healthy pediatric subjects. Urine samples were analyzed using the AspirinWorks™ assay that measures levels of 11-dehydrothromboxane B2. 128 individuals (2 months to 18 years) were identified as healthy and not receiving aspirin.

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Catatonia is a distinct neuropsychiatric syndrome with prominent motor manifestations. Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic syndrome usually precipitated by malignant hypertension. Given the overlapping neuropathology in both syndromes, we present a case of catatonia precipitated by PRES, with full resolution of the former after successful treatment of the latter.

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