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A position statement of the International Pediatric Transplant Association endorsing prioritizing pediatric recipients for deceased donor organ allocation, examining the key ethical arguments that serve as the foundation for that position, and making specific policy recommendations to support prioritizing pediatric recipients for deceased donor organ allocation globally.

Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM-1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM-1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0-13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, -0.33). Urine platinum was not associated with postinfusion AKIor KIM-1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.

Reduced exercise capacity can predispose solid organ transplant (SOT) recipients to higher risk of diabetes, cardiovascular complications, and mortality and impact their quality of life. This systematic review and meta-analysis investigated the effects of exercise training (versus no training) in adult SOT recipients. We conducted an electronic search of randomized controlled trials reporting on exercise interventions in SOT recipients. Primary outcomes were exercise capacity, quadriceps muscle strength, and health-related quality of life (HRQoL). Twenty-nine articles met the inclusion criteria. In 24 studies, there were either high risk of bias or some concerns about the potential risk of bias. There was an increase in exercise capacity (VO2 peak) (SMD: 0.40; 95%CI 0.22-0.57; P = 0.0) and quadriceps muscle strength (SMD: 0.38; 95%CI 0.16-0.60; P = 0.001) in the exercise vs control groups. There were also improvements in several domains of the SF-36. Diastolic blood pressure improved in the exercise group compared to controls (SMD: -0.22; 95%CI -0.41-0.03; P = 0.02). Despite the considerable variation in exercise training characteristics and high risk of bias in the included studies, exercise training improved maximal exercise capacity, quadriceps muscle strength, HRQoL, and diastolic blood pressure and should be an essential part of the post-transplant care.

BACKGROUND There are challenges in achieving and maintaining therapeutic tacrolimus levels after solid organ transplantation (SOT). The purpose of this genome-wide association study (GWAS) was to generate an integrated clinical and genetic prediction model for tacrolimus levels in pediatric SOT. METHODS In a multicenter prospective observational cohort study (2015-18), children

Screening studies have shown that 0.7-4.5% of generally healthy children have isolated diastolic high BP. We therefore studied the characteristics of children with diastolic BP in the elevated and hypertensive ranges according to current guidelines in US children from the National Health and Nutrition Examination Survey (NHANES, 1999-2016).We studied 17,362 children (8-18 years) with BP measured by sphygmomanometry. High BP was categorized as isolated systolic (iSH), isolated diastolic (iDH), or Mixed.Overall, 86.0% (95% CI = 85.0-87.0) of the population had normal BP, 8.7% (8.0-9.3) elevated BP, 4.9% (4.4-5.5) Stage 1, and 0.4% (0.4-0.6) Stage 2. Moreover, 11.1% (10.3-12.0) had iSH, 1.9% (1.5-2.2) iDH, and 1.0% (0.8-1.2) Mixed. Children with iDH were more likely to be female, younger, white, and leaner than those with iSH, with lower rates of overweight/obesity. iDH was generally between normals and iSH. Resting heart rate was significantly higher in iDH even after adjustment for known covariates.Children with iDH may have a distinct clinical picture. A leaner habitus and higher resting heart rate may reflect differences in underlying pathophysiology. Longitudinal follow-up studies are needed to better define the pathogenesis, progression, and long-term prognosis in iDH.Using gold-standard auscultation and 2017 guidelines, isolated diastolic high BP (iDH) is found in 1.9% (95% CI 1.5-2.2) of American children; these children are younger, leaner, more female, and have fewer cardiometabolic risks. Resting heart rate is significantly higher in iDH compared to both normals and iSH even after adjustments for known covariates. Autonomic hyperactivity in iDH may speak to both etiology and therapeutic approaches. iDH appears to be a distinct clinical phenotype characterized by differences in anthropometric measures, sex, age, and resting heart rate. Follow-up studies are clearly needed to clarify its pathogenesis, progression, and prognosis.

Accurate detection of hypertension is crucial for clinical management of pediatric chronic kidney disease (CKD). The 2017 American Academy of Pediatrics childhood hypertension guidelines included new normative blood pressure (BP) values and revised definitions of BP categories. In this study, we examined the effect of applying these changes to the Chronic Kidney Disease in Children (CKiD) cohort compared to use of the 2004 Fourth Report normative data and definitions.Observational cohort study.Children and adolescents in the CKiD cohort.Clinic blood pressure measurements.Blood pressure percentiles and hypertension stages calculated using the 2017 and 2004 guidelines.Agreement analysis compared the estimated percentile and prevalence of high blood pressure based on the 2017 and 2004 guidelines to clinic and combined ambulatory blood pressure readings.The proportion of children classified as having normal clinic blood pressure was similar using the 2017 and 2004 guidelines, but the use of the 2017 normative data classified more participants as having hypertensive-range blood pressure (22% vs. 11%) with marginal reproducibility (kappa= 0.569, 95%CI: 0.538, 0.599). Those identified as hypertensive by the 2017 guidelines had higher levels of proteinuria compared to those identified using the 2004 guidelines. There were substantially more participants with white coat and ambulatory hypertension when using the 2017 guidelines (3.5% vs. 1.5%; and 15.5% vs. 7.9%, respectively). The proportion with masked hypertension was lower using the 2017 guidelines (40.2% vs. 47.8%, respectively) with good reproducibility (kappa= 0.799, 95%CI: 0.778, 0.819), and the percentage of participants with normal ambulatory blood pressure was similar (40.9% vs. 42.9%, respectively), LIMITATIONS: Relationship with long-term progression and target organ damage was not assessed.A greater percentage of children with CKD were identified as hypertensive based on both clinic and ambulatory blood pressure when using the 2017 vs. the 2004 guidelines, and the 2017 guidelines better discriminated those with higher levels of proteinuria. The substantial differences in the classification of hypertension when using the 2004 vs. 2017 guidelines should inform clinical care.

The continuous evolution of metabolomics over the past two decades has stimulated the search for metabolic biomarkers of many diseases. Metabolomic data measured from urinary samples can provide rich information of the biological events triggered by organ rejection in pediatric kidney transplant recipients. With additional validation, metabolic markers can be used to build clinically useful diagnostic tools. However, there are many methodological steps ranging from data processing to modeling that can influence the performance of the resulting metabolomic classifiers. In this study we focus on the comparison of various classification methods that can handle the complex structure of metabolomic data, including regularized classifiers, partial least squares discriminant analysis, and nonlinear classification models. We also examine the effectiveness of a physiological normalization technique widely used in the clinical and biochemical literature but not extensively analyzed and compared in urine metabolomic studies. While the main objective of this work is to interrogate metabolomic data of pediatric kidney transplant recipients to improve the diagnosis of T cell-mediated rejection (TCMR), we also analyze three independent datasets from other disease conditions to investigate the generalizability of our findings.

Oxythiamine is a uremic toxin that acts as an antimetabolite to thiamine and has been associated with cases of Shoshin beriberi syndrome in adults. We sought to identify whether surgical stress and ischemia/reperfusion injury may precipitate functional thiamine deficiency in children peritransplant. We retrospectively analyzed a cohort of pediatric kidney transplant recipients. Oxythiamine levels were measured in pre-transplant serum samples by mass spectrometry and tested for association with severity of lactic acidosis in the first 24 h post-transplant. Secondary outcomes included association with hyperglycemia and indicators of dialysis adequacy (DA). Forty-seven patients were included in the analysis. Median oxythiamine levels differed by modality, measuring 0.67 nM (IQR 0.31, 0.74), 0.34 nM (IQR 0.28, 0.56), and 0.25 nM (IQR 0.17, 0.38) for peritoneal dialysis (PD), hemodialysis (HD), and no dialysis, respectively (p = 0.05). Oxythiamine was associated with 24-h lactate levels (r = 0.38, p = 0.02) and negatively associated with DA (r = − 0.44, p = 0.02). Median oxythiamine levels were higher in patients with poor DA (0.92 nM (IQR 0.51, 1.01) vs. 0.40 nM (IQR 0.24, 0.51), p < 0.01). Sensitivity analysis showed absence of residual association of oxythiamine with 24-h lactate or dialysis modality, but remained significant for DA (p = 0.03). One patient manifested Shoshin beriberi syndrome (oxythiamine 2.03 nM). Oxythiamine levels are associated with DA at transplant. Patients on PD with no residual kidney function and low DA manifest the highest oxythiamine levels and may be at an increased risk for developing acute Shoshin beriberi syndrome in the early post-transplant period.

Introduction The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) has provided insights into 2 distinct diseases. Although outcomes in adults are poor in both diseases, the pediatric literature is scarce and limited to small, single-center cohorts. Methods We conducted a retrospective analysis of 165 pediatric patients across 17 hospitals to compare outcomes between children with IC-MPGN and C3G. Results Forty-two percent of patients initially diagnosed with MPGN were reclassified as C3G after a review of renal biopsy reports. There was a trend toward higher serum creatinine levels in patients with C3G compared with IC-MPGN both at diagnosis (mean 168.9 [range 45.4–292.4] vs. 93.7 [range 70.7–116.6] μmol/l, P = 0.25) and after a mean follow-up time of 4 years (mean 145.0 (range −8.1 to 298.1) vs 99.1 (range 46.3–151.9) μmol/l, P = 0.47), although the estimated glomerular filtration rate (eGFR) was not significantly different. Steroid treatment was associated with a significant improvement in eGFR versus no steroids in C3G (mean +43.0 (range 12.9–73.0) vs. −3.0 (range −23.1 to 17.2) ml/min per 1.73 m2, P = 0.02) but not in IC-MPGN. Overall kidney function was preserved in both groups although hypertension remained prevalent in 42.5% of the cohort at the last follow-up, and the urine protein/creatinine ratio remained elevated (mean 253.8 [range 91.9–415.7] mg/mmol). Conclusion This large pediatric IC-MPGN/C3G cohort revealed nearly half of the patients were misclassified, and there may be a trend toward worse renal prognosis in C3G although they may have greater steroid responsiveness. The overall prognosis appears to be more favorable than in adults; however, persistent hypertension and proteinuria suggest suboptimal disease control., Graphical abstract

Agreement between parent and adolescent ratings of executive function (EF) is not known in adolescents with solid organ transplant (SOT), even though pressing concerns about EF deficits are being raised in this population. The current study investigated EF in adolescents with SOT using parent and self report. Twenty-five adolescents (

Introduction:Adverse symptoms experienced by solid organ transplant recipients remain largely unexplored despite their purported frequency.Objective:To characterize patient perspectives on adverse symptoms, identifying the most problematic symptoms and the perceived cause and treatability, and to evaluate their impact on quality of life (QoL) and medication adherence.Methods:An electronic survey was distributed to members of the Canadian Transplant Association, to characterize perceptions on symptom experience (Modified Transplant Symptom Occurrence and Distress Scale), and QoL (Short Form-12), medication adherence (Basel Assessment of Adherence to Immunosuppressive Medications Scale), demographics, and clinical situation.Results:The questionnaire was distributed to 249 solid organ transplant recipients and achieved a 51% response rate (N = 127). Respondents reported a mean of 25 (standard deviation 10) adverse symptoms each. In women, the most prevalent and distressing symptoms were tiredness, lack of energy, sleep difficulties, difficulty concentrating or memory problems, diarrhea, joint pain, and depression. In men, they were tiredness, flatulence, lack of energy, sleep difficulties, and erectile problems. With the exception of flatulence, these symptoms were more often perceived to be caused by medical conditions rather than by immunosuppressants or other medications. Quality of life was similar to the general public, with mean physical and mental component scores of 47.4 (9.9) and 52.1 (8.2), respectively (relative to a US average of 50 [10]). However, QoL scores inversely correlated to the number of symptoms reported and were higher in patients who perceived all symptoms to be treatable.Conclusion:Adverse symptoms may impact patient well-being. Perceived cause and treatability should be further explored.

Introduction:The objectives of our dissemination project were (1) to disseminate the evidence supporting exercise training in solid organ transplantation to exercise professionals, health-care professionals, physicians, and directors of transplant programs in order to enhance their ability to apply evidence to practice and (2) to build a community of exercise professionals and researchers across Canada.Methods:We used the 5-step Patient-Centered Outcomes Research Institute model for knowledge translation to guide our project: (1) evidence assessment, (2) audience and partner identification, (3) dissemination, (4) implementation, and (5) evaluation. After meeting with experts in the field, conducting a literature review, and identifying an appropriate audience, we took our presentations on the road across Canada.Results:We visited 10 transplant centers and held interactive knowledge translation sessions in each center. To provide sustainability and to facilitate the adoption of the research evidence, we founded the Canadian Network for Rehabilitation and Exercise for Solid Organ Transplant Optimal Recovery network and created its website.Conclusions:Our project raised awareness of the importance of exercise among many health professionals in Canada and built a community of exercise professionals and researchers in the field of transplantation through the rehabilitation network. It also led to the creation of online resources that will facilitate the implementation of rehabilitation programs in transplant centers.

Prognostic biomarkers of T cell–mediated rejection (TCMR) have not been adequately studied in the modern era. We evaluated 803 renal transplant recipients and correlated HLA‐DR/DQ molecular mismatch alloimmune risk categories (low, intermediate, high) with the severity, frequency, and persistence of TCMR. Allograft survival was reduced in recipients with Banff Borderline (hazard ratio [HR] 2.4, P = .003) and Banff ≥ IA TCMR (HR 4.3, P, Alloimmune risk categorization using HLA‐DR/DQ molecular mismatch risk correlates with the severity, frequency, and persistence of T cell–mediated rejection and with graft survival, independent of de novo DSA.

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 (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). RESULTS: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4–12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0–232.7] versus 14.9 [5.4–29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083–9077] versus 1049 [358–3326] pg/mg creatinine; P

Background. 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 (18S-normalized CD3ε, CXCL10 mRNA, and 18S 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 BKV-VP1 mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure. Results. 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. Conclusions. 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.

Background Neuroblastoma is a common solid tumor of childhood and is often associated with hypertension. Potential etiologies contributing to hypertension include renal compression, pain, volume overload, and catecholamine secretion. Cases We completed a single center retrospective review of children with neuroblastoma and ≥stage II hypertension (per Hypertension Canada guidelines) over a 2-year period. All patients (n = 10) had elevated urine normetanephrine levels and eight had intra-abdominal tumors. Four patients had refractory hypertension requiring > three agents, of which three required alpha/beta blockade. Conclusion Although multifactorial, hypertension in neuroblastoma often has a neuroendocrine component. Excess normetanephrine production in neuroblastoma may be a more common hypertensive mechanism than previously appreciated. Urinary normetanephrine elevation could suggest potential neuroendocrine-mediated hypertension.

Male sex is a risk factor for progression of diabetic kidney disease, but the reasons for this predilection are unclear. Here, we demonstrate that cell sex and sex hormones alter the metabolic phenotype of human proximal tubular epithelial cells (PTECs). Male PTECs displayed increased glycolysis, mitochondrial respiration, oxidative stress, apoptosis, and high glucose-induced injury, compared to female PTECs. This phenotype was enhanced by dihydrotestosterone (DHT) and linked to increased mitochondrial utilization of glucose and glutamine. Studies in vivo pointed towards increased glutamine anaplerosis in diabetic male kidneys. Male sex was linked to increased levels of glutamate, TCA cycle, and glutathione cycle metabolites, in PTECs and in the blood metabolome of healthy youth and youth with type 2 diabetes. Conversely, female PTECs displayed increased levels of pyruvate, glutamyl-cysteine, cysteinylglycine, and a higher GSH/GSSG ratio than male PTECs, indicative of enhanced redox homeostasis. Finally, we identified transcriptional mechanisms that control kidney metabolism in a sex-specific fashion. While X-linked demethylase KDM6A facilitated metabolic homeostasis in female PTECs, transcription factor HNF4A mediated the deleterious effects of DHT in male PTECs. This work uncovers the role of sex in glucose/glutamine metabolism, that may explain the roots of sex dimorphism in the healthy and diabetic kidney.

BACKGROUND Physical activity (PA) has been shown to have benefits, including improving health-related quality of life (HRQOL). However, there are few and conflicting studies assessing PA and its relationship with HRQOL in a pediatric solid-organ transplant (SOT) population. The aim of this study was to assess whether overall HRQOL was associated with PA and to determine whether that association was independent of other baseline and contemporaneous clinical and demographic indicators. METHODS A retrospective cross-sectional review was performed on 55 pediatric transplant patients (13 heart, 27 kidney, and 15 liver transplant). PA was measured by PAQ-C/PAQ-A, and HRQOL was measured using PedsQL. Demographics, baseline, and contemporaneous data were collected. RESULTS There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.0 (11.0-18.0) years old at completion of surveys. Median PAQ score was 2.3 (1.6-3.2), PedsQL total score was 77 (65-91), and PedsQL physical functioning score was 88 (72-97). The PedsQL total score was not significantly associated with PAQ score. The PAQ score was significantly associated with physical functioning subscore of the PedsQL (r = 0.37, p

Background We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients. Methods We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada. Patients were enrolled between June 2015 and March 2018 and followed for 6 months. Adherence was assessed at baseline, 3, and 6 months using the BAASIS© self-report tool. Patients were classified as adherent if no doses were missed in the prior 4 weeks. Transplant program directors and nurses completed questionnaires regarding care organization and processes. Results Of the 270 participants, 99 were followed in pediatric programs and 171 in adult programs. Median age was 20.3 years, and median time since transplant was 5 years. At baseline, 71.5% were adherent. Multivariable mixed effects logistic regression models with program as a random effect identified two program-level factors as independently associated with better adherence: minimum number of prescribed blood draws per year for those >3 years post-transplant (per 1 additional) (OR 1.12 [95% CI 1.00, 1.26]; p = .047), and average time nurses spend with patients in clinic (per 5 additional minutes) (OR 1.15 [1.03, 1.29]; p = .017). Conclusion Program-level factors including protocols with a greater frequency of routine blood testing and more nurse time with patients were associated with better medication adherence. This suggests that interventions at the program level may support better adherence.

BACKGROUND The role of antiviral prophylaxis to prevent Epstein-Barr virus (EBV) viremia or posttransplant lymphoproliferative disorder in pediatric solid organ transplant recipients is controversial. We examined whether valganciclovir (VAL) prophylaxis for cytomegalovirus infection was associated with EBV viremia following transplantation in EBV-naive children. METHODS A single-center, retrospective study was conducted of EBV-naive pediatric heart and renal transplant recipients with an EBV-positive donor from January 1996 to April 2017. VAL was tested for association with EBV viremia-free survival in the first 6 months posttransplantation when immunosuppressant exposure is the highest. Survival models evaluated VAL duration, with adjustment for other baseline confounders. RESULTS Among the cohort (n = 44), 3 (6.8%) were heart transplants, 25 (56.8%) received VAL, and 22 (50%) developed EBV viremia in the first-year posttransplantation. Mean time-to-viremia was 143 vs. 90 days for the VAL and no-VAL groups, respectively (p = 0.008), in the first 6 months. Only two patients developed viremia while on VAL. Each additional day of VAL was associated with 1.4% increase in viremia-free survival (p

Rationale & Objective: Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers. Study Design: We used the nominal group technique whereby participants identified and ranked outcomes and explained their priorities. Settings & Participants: Young people with CKD (stages 1-5, dialysis, or transplantation) and their caregivers were purposively sampled from 6 centers across Australia, the United States, and Canada. Analytical Approach: Importance scores were calculated (scale of 0-1), and qualitative data were analyzed thematically. Results: 34 patients (aged 8-21 years) and 62 caregivers participated in 16 groups and identified 48 outcomes. The 5 highest ranked outcomes for patients were survival (importance score, 0.25), physical activity (0.24), fatigue (0.20), lifestyle restrictions (0.20), and growth (0.20); and for caregivers, kidney function (0.53), survival (0.28), infection (0.22), anemia (0.20), and growth (0.17). 12 themes were identified reflecting their immediate and current priorities (wanting to feel normal, strengthening resilience, minimizing intrusion into daily life, imminent threats to life, devastating family burdens, and seeking control over health) and considerations regarding future impacts (protecting health/development, remaining hopeful, concern for limited opportunities, prognostic uncertainty, dreading painful and invasive procedures, and managing expectations). Limitations: Only English-speaking participants were recruited. Conclusions: Kidney function, infection, survival, and growth were the highest priorities for patients with CKD and their caregivers. Young people with CKD also prioritized highly the outcomes that directly affected their lifestyle and sense of normality, while caregiver's highest priorities concerned the long-term health of their child, current health problems, and the financial and family burdens of caring for a child with CKD.

Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.Observational cohort study.Participants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively.Self- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status.mGFR based on iohexol clearance.Linear regression with generalized estimating equations, stratified by age (6, 6-12, 12-18, and ≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations.Self-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups.Small number of children 6 years; lean body mass was estimated.Differences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.

Background: posttransplant diabetes mellitus (PTDM) is a serious complication in kidney transplant recipients (KTRs) due to its negative impact on graft and patient survival. Although reported in 3% to 20% of pediatric KTRs, it has not been as well characterized in adults. In this study we describe incidence and risk factors associated with development of PTDM in pediatric KTRs.Methods: this work is a retrospective cohort study of nondiabetic pediatric patients, aged 6 months to 19 years, who underwent a first kidney transplant during 1995 to 2016. We estimated the cumulative incidence rate and used multivariable logistic regression to identify the diabetogenic risk factors for PTDM.Results: a total of 142 KTRs were included in this study. The cumulative incidence of PTDM was 31% and 14.1% in the first and second year posttransplant, respectively. Significant risk factors for PTDM in the first year after transplant included: dysglycemia in the first 8 to 30 days posttransplant (adjusted odds ratio [aOR], 3.02; 95% confidence interval [CI], 1.21 to 7.53; p=0.018) and use of sirolimus in the first 30 days posttransplant (aOR, 5.33; 95% CI, 1.16 to 24.35; p=0.031). No significant association was found with typical diabetogenic factors.Conclusions: the incidence of PTDM is high among pediatric KTRs. Independent risk factors associated with PTDM included meeting the criteria for dysglycemia or diabetes and sirolimus use in the first month posttransplant. Typical diabetogenic risk factors for type 2 diabetes were not associated with increased risk. This study provides valuable information for posttransplant medical care and future research.

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. METHODS We examined symptoms of anxiety, depression, trauma, and medical procedure anxiety-specifically, fear and avoidance of needles-in youth who had received a kidney, liver, or heart transplant. Parent-report on child mental health symptoms was also collected. RESULTS Data were obtained for 56 youth. Most children did not endorse clinically significant symptoms of depression. In contrast, 20% of parents reported symptoms of depression in their child that exceeded clinical cutoffs. Parents also reported higher levels of anxiety in their children than did the children themselves. Indeed, on average, children reported lower levels of depression and anxiety than would be expected in a general population. On a trauma measure, 22.6% of youths' scores were above clinical cutoffs, with girls scoring higher than boys. Finally, 10.9% of children stated that they attempted to avoid needles because of fear. Once again, girls reported higher needle fear scores than boys and younger patients reported experiencing higher levels of needle fear. CONCLUSIONS Anxiety, depression, post-traumatic stress, and needle fear are important psychological parameters that should be considered in the evaluation of pediatric patients with solid organ transplant, as part of their routine post-transplant care.

Living with end-stage organ failure is associated with an accumulation of traumatic medical events, and despite recovery after solid-organ transplantation (SOT), many children continue to exhibit lower quality of life (QOL). Few studies have examined the relationship between post-traumatic stress disorder (PTSD) and QOL among pediatric SOT recipients. We conducted a retrospective, cross-sectional review of 61 pediatric SOT recipients (12 heart, 30 kidney, and 19 liver) to evaluate the association of PTSD with self-reported QOL. PTSD was measured by the Child Trauma Screening Questionnaire (CTSQ), and QOL was measured using the PedsQL and PedsQL Transplant Module (PedsQL-TM) surveys. Demographics, baseline, and contemporaneous factors were tested for independent association. SOT recipients were 15.2 (12.1-17.6) years old at survey completion. Median CTSQ score was 2 (1-3), highest in kidney recipients, and 13% were identified as high risk for PTSD. Median PedsQL score was 83 (70-91) and significantly associated with the CTSQ score (r = -.68, p < .001). Median PedsQL Transplant Module score was 89 (83-95) and similarly associated with the CTSQ score (r = -.64, p < .001). Age at time of surveys and presence of any disability were also independently associated with PedsQL and PedsQL-TM, respectively. When adjusted for Emotional Functioning, CTSQ remained associated with PedsQL subscores (r = -.65, p < .001). Trauma symptoms are a major modifiable risk factor for lower self-perceived QOL and represent a potentially important target for post-transplant rehabilitation. Additional research is needed to understand the root contributors to PTSD and potential treatments in this population.

This chapter proposes a summary of the current understanding of kidney allograft rejection, evolving from a traditional conceptualization of discrete episodes to a model that recognizes phases of immune activation directed toward the allograft. This starts with detection of well-understood forms of early T cell-mediated rejection (TCMR) or antibody-mediated rejection (AMR) that typify initiation of allograft directed immune injury, and maturation to more complex and chronic forms of rejection that are characterized most often by integrated T and B responses and memory. The risk of progression to chronic forms of rejection may depend on the degree with which alloimmune responsiveness is consistently subdued by immunosuppressant medication, but also the degree with which either the innate and cognate effector responses are secondarily activated or by which adaptive, regulatory responses restrain inflammation.

Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented.Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults.Observational prospective cohort study.Six Canadian oncology centers (3 pediatric, 1 adult and 2 both).Three hundred adults and 300 children planned to receive cisplatin therapy.During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort.Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival.It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge.ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices.Le cisplatine, un agent utilisé en chimiothérapie pour traiter les tumeurs solides, entraîne de l’insuffisance rénale aiguë (IRA); un facteur de risque connu de néphropathie chronique et de mortalité. Le diagnostic de l’IRA repose sur des biomarqueurs qui ne sont mesurables qu’après l’apparition d’une lésion rénale et d’une déficience fonctionnelle; ce qui empêche le diagnostic et le traitement précoce de la maladie. La métabolomique s’efforce d’établir le profil des métabolites impliqués dans le métabolisme des tissus cellulaires en relation avec des facteurs liés à la maladie ou au patient. Une étude canadienne portant sur la métabolomique et la néphrotoxicité du cisplatine (ACCENT) s’est amorcée, elle explore la puissance de la métabolomique dans l’identification de nouveaux biomarqueurs permettant de prédire le risque de néphrotoxicité du cisplatine et d’en distinguer la présence. L’objectif étant de mettre en œuvre des stratégies d’intervention précoce, dès l’apparition de l’IRA, et de limiter la gravité de la maladie.Décrire la conception et la méthodologie de l’étude ACCENT. Cette étude vise à établir et à valider des profils métabolomiques, dans l’urine et le sérum, associés au risque de néphrotoxicité médiée par le cisplatine chez les enfants et les adultes.Étude de cohorte prospective.Six centres canadiens d’oncologie (trois centres pédiatriques, un centre pour adultes et deux centres mixtes).L’étude porte sur 300 adultes et 300 enfants pour qui un traitement par cisplatine est prévu.L’IRA sera confirmée par mesure de la créatinine et des électrolytes dans le sérum et l’urine au cours de deux cycles de perfusion de cisplatine. De nombreuses variables relatives au patient et à la maladie seront recueillies prospectivement avant et pendant le traitement. Les analyses métabolomiques des échantillons de sérum et d’urine seront effectuées par spectrométrie de masse. Une approche métabolomique non ciblée sera utilisée pour analyser les échantillons avant et après les perfusions de cisplatine pour identifier les biomarqueurs candidats d’une IRA découlant du traitement par cisplatine. Les métabolites candidats seront validés dans une cohorte indépendante.Les patients seront recrutés avant le premier cycle de cisplatine. Le sang et l’urine seront recueillis à des moments précis, soit avant et pendant le traitement; plus précisément lors de la première perfusion, puis d’une perfusion subséquente au cours du traitement contre le cancer. Le principal critère d’évaluation est la présence d’IRA, laquelle sera établie selon la définition classique fondée sur la mesure de la créatinine sérique et d’une autre définition fondée sur les anomalies électrolytiques. Un examen des dossiers trois mois après la fin du traitement par cisplatine sera effectué afin de documenter la santé rénale et la survie des patients.Il pourrait être impossible de corriger tous les facteurs confusionnels mesurés et non mesurés lors de l’évaluation de la prédiction de l’IRA à l’aide de profils de métabolites. La collecte de données sur plusieurs sites sera un défi.ACCENT est la plus vaste étude portant sur des enfants et des adultes traités avec le cisplatine; cette étude tente de revoir le modèle actuel en utilisant la métabolomique pour diagnostiquer l’IRA. L’identification de biomarqueurs permettant de prédire et de détecter l’IRA chez les enfants et les adultes traités par cisplatine pourrait grandement éclairer les futures études et pratiques cliniques.ClinicalTrials.gov, insuffisance rénale induite par le cisplatine, NCT04442516.

Purpose Patient-reported outcome measures (PROMs) are standardized instruments used to collect data about the subjective assessment of medical care from the patient perspective. Implementing PROMs within pediatric clinical settings has gained increasing importance as health services prioritize patient-centred pediatric care. This study explores the perspectives of pediatric solid organ transplant patients, caregivers, and healthcare practitioners (HCPs) on implementing PROMs into clinical practice. Methods Qualitative description methods were used to elicit stakeholder perspectives. Semi-structured interviews were conducted across five Canadian transplant centres. Purposive sampling was used to obtain maximum variation across age, gender, and transplant program for all participants, as well as discipline for HCPs. Results The study included a total of 63 participants [patients (n = 20), caregivers (n = 22) and HCPs (n = 21)]. Nearly all participants endorsed the implementation of PROMs to enhance pediatric transplant clinical care. Three primary roles for PROMs emerged: (1) to bring a transplant patient’s overall well-being into the clinical care conversation; (2) to improve patient communication and engagement; and, (3) to inform the practice of clinical pediatric transplant care. Insights for effective implementation included completing electronic PROMs remotely and prior to clinical appointments by patients who are eight to 10 years of age or older. Conclusions This study contributes to current research that supports the use of PROMs in clinical pediatric care and guides their effective implementation into practice. Future directions include the development, usability testing, and evaluation of a proposed electronic PROM platform that will inform future research initiatives.

ER-Tac, taken once per day, is associated with improved adherence. This study examined the potential patient and clinical factors that influence clinicians to convert pediatric patients from immediate-release to ER-Tac. This prospective multi-center observational study followed Canadian pediatric kidney transplant recipients up to 5 years post-transplant. Cox Proportional Hazards Regression was used to examine the influence of factors on conversion to ER-Tac. Sixty-six participants were included in this analysis. For every additional year of age at the time of transplant, the likelihood of conversion was more than doubled (HR 2.54, CI 1.83, 3.54, P

Kidney transplantation increases life expectancy and improves quality of life for children with end-stage kidney disease, yet sequelae of transplantation and treatment make it difficult for transplant recipients to enjoy health and quality of life similar to their healthy peers. The NAPRTCS network was among the first to use multicenter data to inform improvements in care and outcomes for children with a kidney transplant through observational research. Now, with new technologies and unprecedented access to data, it is possible to create learning health systems as envisioned by the US National Academy of Sciences to seamlessly integrate research and continuous improvement of clinical care. In this review, we present two pre-eminent North American networks focused on using multicenter data to drive improved care and outcomes for children with a kidney transplant. Whereas, for the past 30 years NAPRTCS has focused on discovery of best practices through observational research and clinical trials, the Improving Renal Outcomes Collaborative, established in 2016, engages patients, families, clinicians, and researchers in redesigning the healthcare delivery system to enable practice change and continuous improvement of health outcomes. We discuss the history and past contributions of these networks, as well as current activities, barriers, and potential future solutions to more fully realize the vision of a true learning health system for pediatric kidney transplant recipients.

After 2 decades as a low-cost transplant centre in India, our rates of kidney transplantation are low compared to the burden of end-stage kidney disease (ESKD). We performed this study to identify possible barriers inhibiting paediatric kidney transplant and to assess the outcomes of paediatric ESKD. A retrospective chart review of ESKD patients (2013 - 2018) at a tertiary paediatric nephrology centre was conducted. Medical/non-medical barriers to transplant were noted. Patient outcomes were classified as "continued treatment," "lost to follow-up (LTFU)" or "died." Of 155 ESKD patients (monthly income 218 USD [146, 365], 94% self-pay), only 30 (19%) were transplanted (28 living donor). Sixty-five (42%) were LTFU, 19 (12%) died, and 71 (46%) continued treatment. LTFU/death was associated with greater travel distance (300 km [60, 400] vs 110 km [20, 250] km, P

BACKGROUND Children are at high risk for subclinical rejection, and kidney biopsy is currently used for surveillance. Our objective was to test how novel rejection biomarkers such as urinary CXCL10 may influence clinical decision-making to indicate need for a biopsy. METHODS A minimum dataset for standard decision-making to indicate a biopsy was established by an expert panel and used to design clinical vignettes for use in a survey. Pediatric nephrologists were recruited to review the vignettes and A) estimate rejection risk and B) decide whether to biopsy; first without and then with urinary CXCL10/Cr level. Accuracy of biopsy decisions was then tested against the biopsy results. IRA was assessed by Fleiss Kappa (κ) for binary choice and ICC for probabilities. RESULTS Eleven pediatric nephrologists reviewed 15 vignettes each. ICC of probability assessment for rejection improved from poor (0.28, P

BACKGROUND Due to a lack of consensus on SB for pediatric kidney transplant recipients, we evaluated the yield and clinical utility of SB findings at various time points post-transplant. METHODS Patients transplanted at a single institution between 2014 and 2020 with at least one SB at 1.5, 3, 6, 12, and 24 months post-transplant were included. Additional biopsies were done for indication (IB). TCMR was classified by Banff criteria (score ≥i1t1). RESULTS Forty-seven patients had 142 biopsies (SB = 113, IB = 29); 19 (40.4%) of whom experienced at least one TCMR episode in the first-year post-transplant. The greatest SB yield of any pathologic abnormality was at 6 months (57.1%; P

Early TCMR surveillance with protocol kidney biopsy is used differentially among pediatric kidney transplant centers. Little has been reported about actual center-based differences, and this variability may influence TCMR ascertainment, treatment, and monitoring more broadly.Data from the PROBE multicenter study were used to identify patients from centers conducting ESB or LSIB. ESB was defined as50% of patients having at least 1 surveillance biopsy in the first 9 months. Patients were compared for number of biopsies, rejection episodes, treatment, and follow-up monitoring.A total of 261 biopsies were performed on 97 patients over 1-2 years of follow-up. A total of 228 (87%) of biopsies were performed in ESB centers. Compared to LSIB centers, ESB centers had 7-fold more episodes of TCMR diagnosed on any biopsy [0.8 ± 1.2 vs 0.1 ± 0.4; P .001] and a 3-fold higher rate from indication biopsies [0.3 ± 0.9 vs 0.1 ± 0.3; P = .04]. The proportion of rejection treatment varied based on severity: Banff borderline i1t1 (40%);i1t1 and Banff 1A (86%); and ≥ Banff 1A (100%). Biopsies for follow-up were performed after treatment in 80% of cases (n = 28) of rejection almost exclusively at ESB centers, with 17 (61%) showing persistence of TCMR (≥i1t1).Practice variation exists across Canadian pediatric renal transplant centers with ESB centers identifying more episodes of rejection. Additionally, treatment of Banff borderline is not universal and varies with severity regardless of center type. Lastly, follow-up biopsies are performed inconsistently and invariably show persistence of rejection.

PA has been shown to have benefits in SOT patients. Studies assessing physical activity levels and its correlates in a pediatric solid-organ transplant population are limited. The aim of this study was to assess PA levels and identify baseline and contemporaneous factors that contribute to PA in a pediatric SOT population. A retrospective cross-sectional review was performed on 58 pediatric transplant patients (16 heart, 29 kidney, and 13 liver transplant). PA was measured by PAQ-C or PAQ-A. Demographics, baseline, and contemporaneous factors were collected. There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.2 [12.3-17.3] years old at time of completing the PAQ. Median PAQ score was 2.2 [1.7-2.9]. There were no significant differences in PAQ scores between organ transplant type or between genders. Lower PAQ score was associated with sensory disability (9 vs 49 without disability; P =

Introduction: Mental health comorbidities are common in persons with type 2 diabetes (T2D). The magnitude of mental health comorbidities in youth with T2D and possible protective factors against comorbidities, remain unclear, as previous studies have not compared outcomes with population-based samples or included measures of resilience. Methods: We performed a cross-sectional analysis of 178 Indigenous youth (15 yrs IQR: 13-17 yrs) with T2D from the iCARE cohort study and 270 randomly sampled population-based controls (15-24 yrs), from the Canadian Community Health Survey - Mental Health Component. Overall positive mental health and flourishing were assessed with the Mental Health Continuum-Short Form. Depression, anxiety and severe mental illness (SMI) were assessed with the Kessler Distress Scale. Measures of resilience were assessed in youth with T2D using the 64-question Resiliency Scales for Children and Adolescents. Results: Youth with T2D, were more likely to be female (65 vs. 49%), Indigenous (96 vs. 29%), live remotely (70 vs. 26%) and within a low income neighbourhood (p Conclusion: Youth with T2D live with a profound degree of mental health comorbidities relative to the general population of in Manitoba, Canada. Future studies are required to address the specific mental health needs youth with T2D and determined best clinical care practices. Disclosure J. Mcgavock: None. B. Wicklow: None. E. Sellers: None. K. Kroeker: None. T. Blydt-Hansen: None. A. Dart: None. Funding Canadian Institutes of Health Research; Diabetes Canada; Research Manitoba

Background: Youth living with type 2 diabetes (T2D) are characterized by an increased cardiovascular disease (CVD) risk profile. It is unclear if regular vigorous intensity physical activity (PA) modifies this CVD risk. Methods: Using a cross-sectional design, we compared cardiometabolic risk factors among 164 youth with T2D from the The Improving renal Complications in Adolescents with T2D through REsearch (iCARE) cohort, stratified according to participation in vigorous intensity organized sport. Outcomes of interest were HbA1c, ambulatory blood pressure (BP) parameters from 24 hr monitoring, hypertension according to 2017 American Academy of Pediatrics criteria and albuminuria determined from first morning urine samples. The main exposure, regular (≥ 3 days/week) participation in vigorous intensity organized sport was determined from a validated questionnaire (Adolescent Physical Activity Questionnaire). Results: Youth were 15 ± 3 yrs, 78% lived in a rural town, 68% were girls, mean BMI Z score was 2.4 ± 1.1 and mean HbA1c was 9.6 ± 2.6%. Youth that participated in regular vigorous intensity organized sport (40%; n=67) achieved nearly twice the dose of PA than less active peers (176 vs. 108 MET-HR/week; p=0.001). After adjusting for duration of diabetes, BMI Z score, sex and current smoking status, youth with T2D who engaged in regular vigorous intensity organized sport displayed lower HbA1c (9.1%, vs. 9.9% p = 0.052), diastolic BP (70 vs. 73 mmHg, p = 0.002) and diastolic load (20 vs. 26%, p = 0.023). Compared to youth that did not participate in regular vigorous intensity organized sport, those who did displayed a lower odds of albuminuria (OR: 0.40 95% CI: 0.19-0.84) and hypertension (OR: 0.39 95% CI: 0.16-0.95). Conclusions: Among youth living with T2D, self-reported frequent participation in vigorous organized sport is associated with lower CVD risk. These data need to be confirmed with prospective observational and experimental data. Disclosure J.L. Slaght: None. A. Dart: None. T. Blydt-Hansen: None. E. Sellers: None. B. Wicklow: None. J. Mcgavock: None. Funding Diabetes Canada (OG-3-11-3354-AD); Heart and Stroke Foundation of Canada; Canadian Institutes of Health Research (MOP-142309)

This cohort study examines the rate of and risk factors associated with acute kidney injury in children treatment who receive cisplatin infusions., Key Points Question What are the characteristics and risk factors associated with acute kidney injury among children receiving cisplatin infusions? Findings In this cohort study of 159 cisplatin-treated children, 16% to 30% developed acute kidney injury during earlier (first or second cycle) and later (second to last or last cycle) cisplatin infusion treatment and 70% developed electrolyte disturbances. Cancer type and preinfusion kidney function were significantly associated with acute kidney injury risk at earlier and later infusions, and cisplatin dose was associated with acute kidney injury risk at later infusions. Meaning The findings suggest that acute kidney injury is common during cisplatin infusions and that rate and risk factors differ at earlier vs later infusions., Importance Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. Objective To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. Design, Setting, and Participants This prospective cohort study examined children (aged

AIMS/HYPOTHESIS Youth with type 2 diabetes (T2D) have high rates of obesity, hypertension and suboptimal glycemic control. We hypothesized that renin-angiotensin system (RAS) activation is present in youth with T2D and associated with poor glycemic control and renal outcomes. METHODS Cross-sectional analysis of 183 youth with T2D and 100 controls from the Improving renal Complications in Adolescents with T2D through REsearch cohort. Diabetes youth stratified by urine albumin:creatinine ratio (ACR) < or ≥2 mg/mmol. RAS levels measured with enzyme-linked immunosorbent assay (ELISA) and enzyme activities by synthetic substrates. In T2D, levels log transformed and Tobit linear regressions evaluated for associations with hemoglobin A1c (HbA1c), mean arterial pressure (MAP), estimated glomerular filtration rate (eGFR), ACR. RESULTS Youth were 14 to 15 years, with diabetes duration 1.7 to 1.8 years; 21.3% albuminuria. Serum: differences in plasma renin activity (