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Background: Hypercalciuria is the most common risk factor for kidney stone formation, including in pediatric patients. However, the etiology is often unknown and children are frequently diagnosed with idiopathic hypercalciuria. Nearly 50% of children with hypercalciuria have a first-degree relative with kidney stones, suggesting a strong genetic basis for this disease. A failure of calcium reabsorption from the proximal nephron is implicated in the pathogenesis of hypercalciuria. Claudin-2 is a tight junction protein abundantly expressed in the proximal tubule. It confers paracellular permeability to calcium that is essential for transport across the proximal tubule where the majority of filtered calcium is reabsorbed., Objective: Our objective was to examine the frequency of coding variations in CLDN2 in a cohort of children with idiopathic hypercalciuria., Design: Mixed method including retrospective chart review and patient interview, followed by genetic sequencing., Setting: Three tertiary care centers in Canada., Patients: Children (age 1-18 years) with idiopathic hypercalciuria. Patients with other causes of hypercalciuria were excluded., Methods: Data were collected from 40 patients with idiopathic hypercalciuria. Informed consent to collect DNA was obtained from 13 patients, and the final and only coding exon of CLDN2 was sequenced., Results: The majority of patients were male, white, and had a positive family history of kidney stones. Parathyroid hormone levels were significantly lower than the reference range ( P < .001). The levels of 1,25-dihydroxyvitamin D were also significantly higher in our patient cohort, relative to the reference range ( P < .001). Sequence analysis of CLDN2 did not identify any coding variations., Limitations: Sequencing analysis was limited to the final coding exon and small sample size., Conclusions: CLDN2 coding variations are not a common cause of idiopathic hypercalciuria in Canadian children. Further study is needed to determine the causes of hypercalciuria in pediatric patients and develop targeted therapies., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RTA work closely with Dr Hartwig as a member of the KRESCENT leadership team (she is a handling editor)., (© The Author(s) 2022.)

Purpose of Program: Integrated knowledge translation (IKT) is a collaborative approach whereby knowledge created through health research is utilized in ways that are relevant to the needs of all stakeholders. However, research teams have limited capacity and know-how for achieving IKT, resulting in a disconnect between the generation and application of knowledge. The goal of this report is to describe how IKT research was achieved across a large-scale, patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD)., Sources of Information: Resources to facilitate knowledge translation (KT) planning across the network were developed by the Can-SOLVE CKD Knowledge User/Knowledge Translation Committee with reference to established Canadian KT and patient engagement tools and frameworks, review of the published and gray literature, and expertise of committee members., Methods: The Can-SOLVE CKD Knowledge User/Knowledge Translation Committee consisting of patient partners, health care providers, policymakers, and researchers provided oversight of the development and implementation of the network's IKT initiatives. Guided by its strategic framework, the committee developed KT planning templates and review checklists to assist network projects with preparing for dissemination, implementation, and scale and spread of their interventions. The committee has acted in a consultative capacity to facilitate IKT across network initiatives and has supported capacity building through KT activities aimed at network membership and knowledge users more broadly., Key Findings: The Can-SOLVE CKD Knowledge User/Knowledge Translation Committee established a nation-wide strategy for KT infrastructure and capacity building. Acting as a knowledge intermediary, the committee has connected research teams with knowledge users across Canada to support practices and policies informed by evidence generated by the network. The committee has developed KT initiatives, including a Community of Practice, whereby participants across different regions and disciplines convene regularly to share health research knowledge and communications strategies relevant to the network. Critically, patients are engaged and contribute throughout the research process. Examples of IKT activities from select projects are provided, as well as ways for sustaining the network's KT platform., Limitations: The KT resources developed by the committee were adapted from other established resources to meet the needs of the network and have not undergone formal evaluation in this context. Given the broad scope of the network, resources to facilitate implementation and knowledge user engagement may not meet the needs of all initiatives and must be tailored accordingly. Knowledge barriers, including a lack of information and skills related to conceptual and practical aspects of KT, among network members provided a rationale for various KT capacity-building initiatives., Implications: The approach described here offers a practical method for achieving IKT, including how to plan, implement, and sustain initiatives across large-scale health research networks. Within the context of Can-SOLVE CKD, these efforts will shorten knowledge-practice gaps through producing and applying relevant research to improve the lives of people living with kidney disease., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Purpose of Review: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients., Sources of Information: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD., Methods: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions., Key Findings: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool., Limitations: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.M.H. has received investigator-initiated research funding from OPKO Health, Inc (OPKO Renal Division) and Sanofi. R.A.M. has received research funding from the Patient-Centered Outcomes Research Institute (PCORI), the American Society of Hematology (ASH), and the American College of Rheumatology (ACR). R.T.A. has received consulting honoraria from Ardelyx, Inc and from Advicenne. M.B. has received honoraria for advisory board membership with Otsuka Canada Pharmaceutical Inc (OCPI) and AstraZeneca. M.U.B. has received honoraria for consultation, advisory board membership, speaking engagements, or research funding from Janssen, OCPI, and Sanofi. G.K. declared no conflicts of interest. F.M.-W. has received honoraria for conferences, advisory board membership, or research funding from Amgen Inc, Otsuka Canada Pharmaceutical Inc, and Sanofi. M.R. declared no conflicts of interest. R.W. declared no conflicts of interest. P.D.A. declared no conflicts of interest. P.F. has no conflicts of interest. A.G. declared no conflicts of interest. K.K.J. has received honoraria for consultation or advisory board membership from Boehringer Ingelheim, Baxter, Amgen Inc, Sanofi, Eli Lilly and Company, LEO Pharma Inc Canada, and AstraZeneca. M.K. declared no conflicts of interest. B.A.K. declared no conflicts of interest. S.M. has received honoraria for consultation, advisory board membership, research funding, unrestricted grants, and educational grants from the Ontario Ministry of Health, NGX, Health Canada, Nutrigenomix Inc, Mitacs, Central East Local Health Integration Network, Ontario Renal Network (ORN), Sanofi, Shire, Amgen Inc, Sanofi Genzyme, Boehringer Ingelheim, and Baxter. K.M. declared no conflicts of interest. A.M. declared no conflicts of interest. M.P. declared no conflicts of interest. C.R. declared no conflicts of interest. S.D.S. has received honoraria for consultation, advisory board membership, and Canadian Medical Education (CME) lectures from the, Sanofi, Pfizer Inc, Janssen Inc, Amgen Inc, and Otsuka Canada Pharmaceutical Inc. A.J.V. has received honoraria for consultation from Paladin Labs Inc. D.Z. has received investigator-initiated research funding from Sanofi and has been a member of advisory boards for Otsuka Canada Pharmaceutical Inc, and Amgen Inc. C.M.C. has received honoraria for consultation, advisory board membership, or research funding from the Ontario Ministry of Health, Sanofi, Pfizer Inc, LEO Pharma Inc Canada, Astellas, Janssen Inc, Amgen Inc, Boehringer Ingelheim, and Baxter., (© The Author(s) 2020.)

Purpose of the Review: The Royal College of Physicians and Surgeons of Canada, with its Competence by Design initiative, is adopting the principles of competency-based medical education for residency training and continuing professional development. This initiative is being undertaken to meet the new standards of medical education in Canada, which include social accountability to meet performance-based outcomes of training. Nephrology is poised to implement Competence by Design into residency training in July 2018 and initiate a continuous quality improvement cycle to periodically renew and update the training requirements to be socially accountable and relevant in the modern age of medicine. The purpose of this review is to describe the process of entrustable professional activity and required training experience development and how they will affect subspecialty training in Canada., Sources of Information: The construct of competency-based medical education was derived from existing literature searches of the medical education literature, including documentation provided by the Royal College of Physicians and Surgeons of Canada. The content for each entrustable professional activity and milestone was derived by consensus from the community expertise of the working group, existing speciality training requirements, and elements of training requirements that the Royal College has been mandated to superimpose on all training requirements to meet societal expectations., Methods: The Royal College Specialty Committee in Nephrology participated in 2 years of preparation for this implementation, which has included the creation of a new educational design for the discipline and the elucidation of entrustable professional activities to describe the scope of nephrology practice and to guide teaching, learning, and assessment in residency, and ultimately maintenance of competence in practice., Key Findings: This article introduces the set of entrustable professional activities for adult and pediatric nephrology and describes the national consultation as part of an ongoing quality improvement of this work., Limitations: The implementation of Competence by Design will be tested by whether trainees embrace competency-based education by training to just entrustable professional activities, rather than the holistic model idealized in physician training. This is mitigated by the entrustable professional activity development incorporating multiple layers of competencies beyond a procedural skill. Time commitment for faculty will pose additional challenges in increasing the time for assessment of trainees, but is supported by electronic platforms at the Royal College to assist in data gathering and analysis., Implications: Competence by Design in nephrology is an outcomes-based curriculum and assessment platform that aims to train nephrologists to meet societal expectations in an ever-changing and complicated health care system. The goals are to increase safety and professional accountability to society and improve upon the already high standards of training within Canada., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pediatric chronic kidney disease is psychologically, financially, and physically demanding on parents providing care. Parents often feel isolated because of the rarity of the condition, and geographic isolation often compounds this perception in Canada. Many parents seek assistance online for both information and social support., Objective: This study examines an online portal, titled "Ability Online," which was designed to provide support and information to a diverse group of parents using chat facilities, bulletin boards, and e-mail. Specifically, we sought to identify how the technologies offered in this system related to the support and information seeking needs for parents. Secondary aims of determining possible reasons for attrition over time were explored as well., Design: Mixed methodology sequential exploratory design using the qualitative methodology of descriptive interpretation., Setting: Telephone interviews., Patients: Twenty parents of pediatric patients with chronic kidney disease from four Canadian centers who engaged in an online social support system "Ability Online.", Measurements: Interview transcripts generated from 20 taped phone conversations were reviewed from parents who engaged in the online system, and the themes derived from these transcripts served to generate semistructured interview questions that focused on their use of, and perceived benefit from, this technology for social support. Follow-up telephone interviews were then conducted with a 6-person subset of the original group in an effort to further define the impact of technology on their experience. This same smaller cohort provided data on social supports, caregiver satisfaction, and caregiver stress., Results: Many parents experience a progression through which their needs for knowledge and support change over time. Specifically, parents describe a transition from pure information seeking, to seeking parental interaction, mutual support and collaboration, and ultimately to advocacy. Parents described how technology could be used to address those needs., Limitations: Our cohort was slightly more educated and representative of more urban populations than published data reflecting the population of North American pediatric patients living with kidney disease., Conclusions: Our data suggest themes of technology use influencing the goals of online support seeking. While our findings are preliminary, further study may inform Web designers to identify the changing needs of participants in designing such online support networks, and minimize the reasons that participants fail to adopt, or terminate their online experiences., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited., Objective: To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension)., Design: This is a 3-year observational prospective cohort study., Setting: The study includes 12 Canadian pediatric oncology centers., Patients: The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria : Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 or a pre-existing renal transplantation at baseline., Measurements: Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected., Methods: Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines. Procedure: Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes)., Limitations: The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved., Conclusions: ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres., Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care., Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component)., Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics., Patients: 400 patients under 18 years of age to be recruited over 2.5 years., Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups., Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care., Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups., Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres.