Combination Automated Microfluidics Measurement of Urine C-C Motif Ligand 2, CXC-Motif Chemokine 9, CXC-Motif Chemokine 10, and Vascular Endothelial Growth Factor A for Monitoring Patients with a Kidney Transplant.

Key Points: Combining urine C-C motif ligand 2, CXC-motif chemokine 9, CXC-motif chemokine 10, and vascular endothelial growth factor A identifies stable transplant recipients without biopsy-proven acute rejection with >75% specificity and 94% negative predictive value. Measuring four urine analytes in combination using an automated platform is highly efficient (<70 minutes) and reproducible across three independent sites. Automated urine analyte measurement provides critical decision support and outperforms eGFR measurements alone for post-transplantation monitoring.

Evaluating Activated Regulatory T Cells as a Biomarker of Chronic Allograft Inflammation in Pediatric Kidney Transplant Recipients.

Background: There is a need for noninvasive immunological biomarkers that can identify stable kidney allograft immune quiescence to inform individualized immunosuppression.

Methods: We conducted a cross-sectional, pilot cohort study evaluating the relative abundance of regulatory T cells (Tregs) to effector T-cell (Teff) populations as a surrogate marker of long-term graft tolerance. We obtained fresh peripheral blood mononuclear cell samples from stable pediatric kidney transplant recipients, most with recent surveillance biopsies to identify the presence or absence of chronic inflammation.

Risk Factors of Post-Traumatic Stress in Pediatric Solid Organ Transplant Recipients.

Background: Life with end-stage organ failure is accompanied by an accumulation of traumatic medical or surgical experiences. Despite recovery after solid organ transplantation (SOT), many children and adolescents develop post-traumatic stress symptoms (PTSS). PTSS remain underappreciated as a major comorbidity in SOT programs, despite their association with decreased quality of life.

Adrenal insufficiency in pediatric kidney transplantation recipients.

Background: Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients.

Methods: This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects.

Tubular Injury Biomarkers to Predict CKD and Hypertension at 3 Months Post-Cisplatin in Children.

Key Points: Tubular injury biomarkers are not individually strong predictors of 3-month post-cisplatin CKD. When combined with clinical measures, tubular injury biomarkers can predict post-therapy hypertension and identify high-risk patients.

Background: Urine kidney injury biomarkers measured during cisplatin therapy may identify patients at risk of adverse subsequent kidney outcomes.

Sex differences in kidney metabolism may reflect sex-dependent outcomes in human diabetic kidney disease.

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females.

Follow-up biopsies identify high rates of persistent rejection in pediatric kidney transplant recipients after treatment of T cell-mediated rejection.

Background: Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients.

Methods: Patients from two pediatric transplant centers performing standard of care FUB at 1.

Parent and healthcare provider views of live varicella vaccination of pediatric solid organ transplant recipients.

Background: Live attenuated varicella vaccine (LAVV) has historically been contraindicated in children who are immunocompromised due to solid organ transplant (SOT) because of safety concerns. Recently, clinical guidelines were developed that support post-transplant varicella vaccination in selected SOT recipients based on emerging evidence of LAVV safety. This qualitative study sought to explore barriers and facilitators to implementing the new guidelines, as well as acceptability of LAVV among healthcare providers (HCPs) and parents.

Urinary TIMP-2*IGFBP-7 to diagnose acute kidney injury in children receiving cisplatin.

Background: Cisplatin is associated with acute kidney injury (AKI) and electrolyte abnormalities. Urine tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7) may be early cisplatin-AKI biomarkers.

Methods: We conducted a 12-site prospective cohort study with pediatric patients treated with cisplatin (May 2013-December 2017).

Metabolomic identification of predictive and early biomarkers of cisplatin-induced acute kidney injury in adult head and neck cancer patients.

Aim: Cisplatin causes acute kidney injury (AKI) in approximately one third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced AKI. Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI.

Noninvasive testing for mycophenolate exposure in children with renal transplant using urinary metabolomics.

Background: Despite the common use of mycophenolate in pediatric renal transplantation, lack of effective therapeuic drug monitoring increases uncertainty over optimal drug exposure and risk for adverse reactions. This study aims to develop a novel urine test to estimate MPA exposure based using metabolomics.

Methods: Urine samples obtained on the same day of MPA pharmacokinetic testing from two prospective cohorts of pediatric kidney transplant recipients were assayed for 133 unique metabolites by mass spectrometry.

Exploring the Ethical Considerations of Direct Contact in Pediatric Organ Transplantation: A Qualitative Study.

Background: Nonanonymized direct contact between organ recipients and donor families is a topic of international interest in the adult context. However, there is limited discussion about whether direct contact should be extended to pediatric settings due to clinician and researcher concerns of the potential harms to pediatric patients.

Methods: We interviewed pediatric organ recipients, their families, and donorfamilies in British Columbia, Canada, to determine their views on direct contact.

Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.

Background: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes.

Methods: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals.

Vitamin D Toxicity from an Unusual and Unexpected Source: A Report of 2 Cases.

Introduction: Hypervitaminosis D is a relatively uncommon etiology of hypercalcemia. Toxicity is usually caused by very high doses, mostly secondary to erroneous prescription or administration of vitamin D, and less commonly, contaminated foods or manufacturing errors of vitamin D-containing supplements.

Case Presentation: A 16-year-old male, previously healthy, presented with 2-week history of nonspecific symptoms (fatigue, gastrointestinal complaints).

High urinary CXCL10/Cr with onset of Burkitt lymphoma in a pediatric kidney transplant recipient.

Background: Urinary CXCL10/Cr is a promising diagnostic tool for early detection of TCMR in pediatric transplant recipients, and most studies focus on its utility in the context of localized allograft inflammation thus far. Other sources of inflammation that may be detected by CXCL10 are less clear.

Methods: We present a case review of a patient with BL, who was enrolled in a prospective trial of urinary CXCL10 monitoring.

Clinical indicators of slow graft function and outcome after pediatric kidney transplantation.

Background: Lesser degrees of perioperative ischemia-reperfusion injury that does not require dialysis may nonetheless influence allograft outcomes, necessitating evaluation of suitable surrogate indicators of perioperative allograft injury.

Methods: This retrospective analysis of pediatric kidney transplants evaluated two indicators representing pace and completeness of recovery, for association with 12-month estimated glomerular filtration rate (eGFR) and first-year rate of eGFR decline: time to creatinine nadir (TTN) and ratio of recipient/donor unadjusted GFR (uGFR ) at 1-month post-transplant. Donor, recipient, and perioperative risk factors were tested further for association with these 2 indicators.

Child and caregiver perspectives on access to psychosocial and educational support in pediatric chronic kidney disease: a focus group study.

Background: Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin.

Methods: Participants (=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals.

A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial.

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes.

Urinary metabolomics to develop predictors for pediatric acute kidney injury.

Background: Acute kidney injury (AKI) is characterized by an abrupt decline in glomerular filtration rate (GFR). We sought to identify separate early urinary metabolomic signatures at AKI onset (with-AKI) and prior to onset of functional impairment (pre-AKI).

Methods: Pre-AKI (n=15), AKI (n=22), and respective controls (n=30) from two prospective PICU cohort studies provided urine samples which were analyzed by GC-MS and DI-MS mass spectrometry (193 metabolites).

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

Unlabelled: 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.

Methods: 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.

The mental health profiles of pediatric organ transplant recipients.

Background: Solid organ transplantation is the indicated treatment for children with end-stage organ failure. Little is known about the impact of organ transplantation on pediatric transplant recipients' mental health. Symptoms of medical procedure and generalized anxiety, post-traumatic stress, and depression may emerge, despite the successful restoration of organ function.

Height-adjusted lean body mass and its associations with physical activity and kidney function in pediatric kidney transplantation.

Background: Although LBM is positively associated with health outcomes, studies assessing determinants for the accrual of ht-LBM, such as physical activity, are limited. This study aimed to assess ht-LBM levels in pediatric kidney transplant recipients and test its association with baseline and contemporaneous variables, including physical activity.

Methods: A retrospective cross-sectional review was performed on 46 pediatric kidney transplant recipients, and a longitudinal review was performed on a subset of recipients with serial post-transplant (n = 21) and pre/post-transplant (n = 11) ht-LBM measurements.