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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. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. Results: Of 159 children (median [interquartile range [IQR]] age: 6 [2–12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76–110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2–6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2–6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04–6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2–6-month hypertension (AdjOR [95% CI]: 3.64 [1.05–12.62]). Conclusions: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. [ABSTRACT FROM AUTHOR]

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. Methods: Children with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically. Results: We identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child's suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood). Conclusions: Children with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To determine the prevalence of macroalbuminuria and to describe the clinical and renal pathological changes associated with macroalbuminuria in a population of Canadian First Nation children and adolescents with type 2 diabetes. RESEARCH DESIGN AND METHOD -- We conducted a retrospective chart review at a single tertiary care pediatric diabetes center, and a case series was constructed. We collected data on microalbuminuria (≥3 mg/mmol creatinine [26.5 mg/g]) and macroalbuminuria (≥28 mg/mmol creatinine [247.5 mg/g]), estimated glomerular filtration rate, renal pathology, and aggravating risk factors (poor glycemic control, obesity, hypertension, glomerular hyperfiltration, hypercholesterolemia, smoking, and exposure to diabetes in utero). RESULTS -- We reviewed 90 charts of children and adolescents with type 2 diabetes. A total of 53% had at least one random urine albumin-to-creatinine ratio ≥3 mg/mmol (26.5 mg/g). There were 14 of 90 (16%) who had persistent macroalbuminuria at or within 8 years of diagnosis of diabetes. Of these 14 subjects, 1 had orthostatic albuminuria and 3 had spontaneous resolution of albuminuria. A total of 10 had renal biopsies performed. There were 9 of 10 who exhibited immune complex disease or glomerulosclerosis, and none had classic diabetic nephropathy. CONCLUSIONS -- This study suggests that the diagnosis of renal disease in children with type 2 diabetes cannot be reliably determined by clinical and laboratory findings alone. Renal biopsy is necessary for accurate diagnosis of renal disease in children and adolescents with type 2 diabetes and macroalbuminuria. The additional burden of nondiabetic kidney disease may explain the high rate of progression to end-stage kidney failure in this population. [ABSTRACT FROM AUTHOR]

Background: Donor interventions, including medications, protocols, and medical devices administered to donors, can enhance transplantable organ quality and quantity and maximize transplantation success. However, there is paucity of high-quality evidence about their effectiveness, in part because of ethical, practical, and regulatory challenges, and lack of guidance about conduct of donor intervention randomized controlled trials (RCTs)., Methods: With the vision to develop authoritative guidance for conduct of donor intervention RCTs, we convened a workshop of Canadian-United Kingdom experts in organ donation and transplantation ethics, research, and policy to identify stakeholders, explore unique challenges, and develop research agenda to inform future work in this promising field., Results: Donor intervention trials should consider perspectives of broad group of stakeholders including donors, transplant recipients, and their families; researchers in donation and transplantation; research ethics boards; and healthcare providers and administrators involved in donation and transplantation. Unique challenges include (1) research ethics (living versus deceased status of the donor at the time of intervention, intervention versus outcomes assessment in different individuals, harm-benefit analysis in donors versus recipients, consent, and impact on research bystanders); (2) outcome data standardization and linkage; and (3) regulatory and governance considerations., Conclusions: Donor intervention RCTs hold potential to benefit organ transplantation outcomes but face unique research ethics, outcome data, and regulatory challenges. By developing research agenda to address these challenges, our workshop was an important first step toward developing Canada-United Kingdom guidance for donor intervention RCTs that are poised to improve the quality and availability of transplantable organs., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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. Interviews were conducted in two stages, with those who were further removed from the transplant process informing the approach to interviews with those who more recently went throughthe transplant process., Results: Twenty-nine individuals participated in twenty in-depth interviews. The study included participants from three major organ systems: kidney, heart, and liver. Only five participants expressed that direct contact might cause harm or discomfort, while twenty-three indicated they saw significant potential for benefits. Nearly half focused on the harms to others rather than themselves, and nearly two-thirds focused on the benefits for others rather than themselves., Conclusion: There appears to be a community desire for direct contact in pediatric organ transplant programs among those living in British Columbia, Canada. These results suggest a need to revisit the medical community's assumptions around protection and paternalism in our practice as clinicians and researchers.

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 <0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65)., Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes., Competing Interests: T.D. Blydt-Hansen reports having ownership interest in Apple, Hydrogenics, and Royal Bank of Canada; receiving honoraria from Astellas Canada; receiving research funding from Astellas Canada, Canadian Institutes of Health Research, Child and Family Research Institute, Children’s Hospital of Manitoba Research Institute, and Transplant Research Foundation of BC; having consultancy agreements with Astellas Canada, Horizon Canada, Novartis, and Ricordati; and serving as a scientific advisor for or member of BC Transplant, Canadian National Transplant Research Program, International Pediatric Transplant Association (council member), and North American Pediatric Transplant and Collaborative Studies. B.C. Carleton reports serving as a scientific advisor for or member of AEVI Genomic Medicine, United Health Group Pharmacogenomics (on the advisory committee); having consultancy agreements with Dynacare Specialized Diagnostics; receiving research funding from Dynacare Specialized Diagnostics (ended in June 2021) and grants from federal and provincial agencies; and having other interests/relationships with Rare Disease Society. P. Devarajan reports having consultancy agreements with Alnylam, Dicerna, Natera, and Reata; being a coinventor on patents for the use of NGAL as a biomarker of kidney injury; and serving on speakers bureaus for BioPorto Inc., Natera, and Reata. M. Pinsk reports having consultancy agreements with Canadian Agency for Drugs and Technologies in Health (as consultant); serving as an expert witness for legal consultations (multiple); and having other interests/relationships with Canadian Society of Nephrology, International Pediatric Nephrology Association, and Medical Council of Canada. K. R. Schultz reports having consultancy agreements with AVM Biotech, Celgene/Juno, Jazz, and Medpace; receiving honoraria from Bristol Myers Squibb (BMS), Celegene, and Jazz; serving on the data safety monitoring boards for BMS/Juno and Medpace; and serving as a scientific advisor or membership of Jazz. R.T. Tsuyuki reports receiving research funding from AstraZeneca, Merck Canada Inc., and Sanofi; serving as the editor-in-chief for Canadian Pharmacists Journal, and as president, chair, and on the board of directors for Hypertension Canada; receiving honoraria from Emergent Biosolutions and Merck Canada Inc.; and having consultancy agreements with Emergent Biosolutions and Shoppers Drug Mart. M. Zappitelli reports having consultancy agreements with BioPorto Inc., CytoPheryx Inc., and Eloxx Pharmaceuticals; receiving honoraria from Bioporto Inc. and Eloxx Pharmaceuticals; and having other interests/relationships with Canadian Pediatric Nephrologists Association, Canadian Society of Nephrology, and Kidney Foundation of Canada. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

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.

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., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Youth-onset type 2 diabetes is associated with a high burden of renal complications, culminating with end stage kidney disease in early adulthood. The establishment of relevant bioclinical determinants of albuminuria and ultimately progression of chronic kidney disease in youth is critically important to facilitate patient risk stratification and aid in the development of treatment targets and tailored prevention strategies. In response to the important gaps in knowledge, we created a prospective cohort study of youth with type 2 diabetes titled the Improving Renal Complications in Adolescents with Type 2 Diabetes through the REsearch (iCARE) Study., Methods: iCARE is a prospective observational cohort study of individuals with type 2 diabetes diagnosed prior to 18 years of age; the recruitment target was 400 patients. Phase 1 entailed a detailed phenotypic assessment of youth, including anthropometrics, biochemistry, 24-hour ambulatory blood pressure monitoring, overnight urine collections for albumin excretion, renal ultrasound and iohexol-derived glomerular filtration rate. Phase 2 of the study is an evaluation of psychological factors, including hair-derived cortisol; validated questionnaires for perceived stress, distress and resiliency; and a detailed evaluation of systemic and urine inflammatory biomarkers. Annual follow up is planned to assess temporal associations between clinical risk factors and renal outcomes, including progression of albuminuria., Conclusion: This study will provide novel insight into the risk factors for albuminuria and progression of chronic kidney disease in youth with type 2 diabetes. New knowledge generated by this study will inform clinical care, and the infrastructure developed will provide a framework for future intervention studies., (Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This guideline for the use of immunoglobulin (IG) for sensitized patients undergoing solid organ transplantation (SOT) is an initiative of the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products of Canada to (1) provide guidance for Canadian practitioners involved in the care of patients undergoing SOT and transfusion medicine specialists on the use of IG and (2) standardize care, limit adverse events, and optimize patient care. A systematic expert and bibliography literature search up to July 2008 was conducted, with 791 literature citations and 45 reports reviewed. To validate the recommendations, the guideline was sent to physicians involved in SOT in Canada and a patient representative. The recommendations identify (1) sensitized patients undergoing SOT that would have a better survival and decreased morbidity by receiving IG preoperatively, postoperatively, and for the treatment of organ rejection; (2) patients who may not have any benefit from receiving IG; and (3) potential adversities to IG.