The multifaceted links between hearing loss and chronic kidney disease.

Hearing loss affects nearly 1.6 billion people and is the third-leading cause of disability worldwide. Chronic kidney disease (CKD) is also a common condition that is associated with adverse clinical outcomes and high health-care costs. From a developmental perspective, the structures responsible for hearing have a common morphogenetic origin with the kidney, and genetic abnormalities that cause familial forms of hearing loss can also lead to kidney disease. On a cellular level, normal kidney and cochlea function both depend on cilial activities at the apical surface, and kidney tubular cells and sensory epithelial cells of the inner ear use similar transport mechanisms to modify luminal fluid. The two organs also share the same collagen IV basement membrane network. Thus, strong developmental and physiological links exist between hearing and kidney function. These theoretical considerations are supported by epidemiological data demonstrating that CKD is associated with a graded and independent excess risk of sensorineural hearing loss. In addition to developmental and physiological links between kidney and cochlear function, hearing loss in patients with CKD may be driven by specific medications or treatments, including haemodialysis. The associations between these two common conditions are not commonly appreciated, yet have important implications for research and clinical practice.

Hedgehog-GLI mediated control of renal formation and malformation.

CAKUT is the leading cause of end-stage kidney disease in children and comprises a broad spectrum of phenotypic abnormalities in kidney and ureter development. Molecular mechanisms underlying the pathogenesis of CAKUT have been elucidated in genetic models, predominantly in the mouse, a paradigm for human renal development. Hedgehog (Hh) signaling is critical to normal embryogenesis, including kidney development. Hh signaling mediates the physiological development of the ureter and stroma and has adverse pathophysiological effects on the metanephric mesenchyme, ureteric, and nephrogenic lineages. Further, disruption of Hh signaling is causative of numerous human developmental disorders associated with renal malformation; Pallister-Hall Syndrome (PHS) is characterized by a diverse spectrum of malformations including CAKUT and caused by truncating variants in the middle-third of the Hh signaling effector GLI3. Here, we outline the roles of Hh signaling in regulating murine kidney development, and review human variants in Hh signaling genes in patients with renal malformation.

Hedgehog signalling in Foxd1+ embryonic kidney stromal progenitors controls nephron formation via Cxcl12 and Wnt5a.

Congenital anomalies of the kidney and urinary tract (CAKUT) are characterised by a spectrum of structural and histologic abnormalities and are the major cause of childhood kidney failure. During kidney morphogenesis, the formation of a critical number of nephrons is an embryonic process supported, in part, by signalling between nephrogenic precursors and Foxd1-positive stromal progenitor cells. Low nephron number and abnormal patterning of the stroma are signature pathological features among CAKUT phenotypes with decreased kidney function. Despite their critical contribution to CAKUT pathogenesis, the mechanisms that underlie a low nephron number and the functional contribution of a disorganised renal stroma to nephron number are both poorly defined. Here, we identify a primary pathogenic role for increased Hedgehog signalling in embryonic renal stroma in the genesis of congenital low nephron number. Pharmacologic activation of Hedgehog (Hh) signalling in human kidney organoid tissue decreased the number of nephrons and generated excess stroma. The mechanisms underlying these pathogenic effects were delineated in genetic mouse models in which Hh signalling was constitutively activated in a cell lineage-specific manner. Cre-mediated excision of Ptch1 in Foxd1+ stromal progenitor cells, but not in Six2+ nephrogenic precursor cells, generated kidney malformation, identifying the stroma as a driver of low nephron number. Single-cell RNA sequencing analysis identified Cxcl12 and Wnt5a as downstream targets of increased stromal Hh signalling, findings supported by analysis in human kidney organoids. In vivo deficiency of Cxcl12 or Wnt5a in mice with increased stromal Hh signalling improved nephron endowment. These results demonstrate that dysregulated Hh signalling in embryonic renal stromal cells inhibits nephron formation in a manner dependent on Cxcl12 and Wnt5a. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Storytelling for impact: the creation of a storytelling program for patient partners in research.

Storytelling is a powerful means to evoke empathy and understanding among people. When patient partners, which include patients, family members, caregivers and organ donors, share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of driving change in the healthcare system. However, a growing number of patient partners are asked to 'share their story' within health care and research settings without adequate support to do so. This may ultimately widen, rather than close, the gap between healthcare practitioners and people affected by chronic disease in this new era of patient and public involvement in research. To better support patient partners with storytelling in the context of a patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network adapted an existing in-person storytelling workshop for patient educators within a hospital setting. The result is a 6-week virtual program called Storytelling for Impact, which guides patients, family members, caregivers and organ donors in developing impactful stories and sharing them at health care and research events, e.g., conferences. The online series of synchronous workshops is co-facilitated by story coaches, who are program alumni and Can-SOLVE CKD staff with trained storytelling experience. Each story follows a structure that includes a call to action, which aims to positively impact the priority-setting and delivery of care and research in Canada. The program has been a transformational process for many who have completed it, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As result, we have also created an asynchronous online program that can be used by other interested parties outside our network. Patient partners who share their stories can be powerful mediators for inspiring changes in the health care and research landscape, with adequate structured support. We describe two novel programs to support patient partners in impactful storytelling, which are applicable across all health research disciplines. Additional resources are required for sustainability and scale up of training, by having alumni train future storytellers.

Storytelling is a powerful means to evoke empathy and understanding among people. When patient partners share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of improving the healthcare system. However, as a growing number of patient partners are asked to 'share their story' within health care and research settings, there is often not enough tools and resources to support them in preparing their stories in a way that will be impactful for the audience members. Our kidney research network sought to create a novel in-person storytelling program to address this gap within our health research context. The result is a 6-week program called Storytelling for Impact, which guides patient partners­which includes patients, family members, caregivers and organ donors­in developing impactful stories and sharing them in a formal setting. The program is led by story coaches, who are patient partners and staff with trained storytelling experience. Participants are encouraged to include a call to action in their story, which aims to outline clear ways in which health professionals can facilitate positive change in health research or care. Many participants have described the program as transformational, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As a result, we have also created a second online program that can be used by other interested parties outside our network. This paper highlights the adaptation process, content, participant feedback and next steps for the program.

Anatomy and embryology of congenital surgical anomalies: Congenital Anomalies of the Kidney and Urinary Tract.

Congenital anomalies of the kidney and urinary tract or "CAKUT" describes a spectrum of developmental disorders with a range of associated clinical presentations and functional consequences. CAKUT underlies the majority of chronic kidney disease and kidney replacement therapy requirement in children, but functional deterioration can also emerge in adulthood. Understanding the normal embryological processes involved in kidney development allows us to appreciate the timing and sequence of critical events implicated when things go wrong. In this review, we will describe the normal developmental mechanisms and relate this to what we currently know about the pathological processes involved in various forms of CAKUT. We will also review the proposed etiological factors, in particular genetics, involved in CAKUT.

Pallister-Hall syndrome, GLI3, and kidney malformation.

Pallister-Hall syndrome (PHS) is a rare autosomal dominant disease diagnosed by the presence of hypothalamic hamartoma, mesoaxial polydactyly and a truncating variant in the middle third of the GLI-Kruppel family member 3 (GLI3) gene. PHS may also include a wide range of clinical phenotypes affecting multiple organ systems including congenital anomalies of the kidney and urinary tract (CAKUT). The observed clinical phenotypes are consistent with the essential role of GLI3, a transcriptional effector in the hedgehog (Hh) signaling pathway, in organogenesis. However, the mechanisms by which truncation of GLI3 in PHS results in such a variety of clinical phenotypes with variable severity, even within the same organ, remain unclear. In this study we focus on presentation of CAKUT in PHS. A systematic analysis of reported PHS patients (n = 78) revealed a prevalence of 26.9% (21/78) of CAKUT. Hypoplasia (± dysplasia) and agenesis were the two main types of CAKUT; bilateral and unilateral CAKUT were reported with equal frequency. Examination of clinical phenotypes with CAKUT revealed a significant association between CAKUT and craniofacial defects, bifid epiglottis and a Disorder of Sex Development, specifically affecting external genitalia. Lastly, we determined that PHS patients with CAKUT predominately had substitution type variants (as opposed to deletion type variants in non-CAKUT PHS patients) in the middle third of the GLI3 gene. These results provide a foundation for future work aimed at uncovering the molecular mechanisms by which variant GLI3 result in the wide range and severity of clinical features observed in PHS.

Program Report: Can-SOLVE CKD Network Presents an Inclusive Method for Developing Patient-Oriented Research Tools.

PURPOSE OF PROGRAM: Given the growing interest in patient-oriented research (POR) initiatives, there is a need to provide relevant training and education on how to engage with patients as partners on research teams. SOURCES OF INFORMATION: As part of its mandate to develop appropriate training materials, the patient-oriented renal research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD), established a training and Mentorship Committee (TMC). METHODS: The committee brings together a unique combination of Indigenous and non-Indigenous patient partners (including caregivers, family members, and living donors), researchers, as well as patient engagement and knowledge translation experts, combining a multitude of perspectives and expertise. Following an assessment of training needs within the network, the TMC undertook the co-development of 5 learning modules to address the identified gaps. Subsequently, the committee divided into working groups tasked with developing content using a consultive and iterative approach informed by the DoTTI framework for building web-based tools for patients. In addition, the TMC embodied the guiding principles of inclusiveness, support, mutual respect, and co-building as set out by the Patient Engagement Framework through the Strategy for Patient-Oriented Research (SPOR) of the Canadian Institutes of Health Research. KEY FINDINGS: The 5 new modules include: A Patient Engagement Toolkit, Storytelling for Impact, Promoting Kidney Research in Canada (KidneyPRO), Wabishki Bizhiko Skaanj Learning Pathway, and Knowledge Translation. The TMC's approach to developing these modules demonstrates how a diverse group of stakeholders working together can create tools to support high-quality POR. This also provides a roadmap for other health research entities interested in developing similar tools within their unique domains. LIMITATIONS: The landscape of patient engagement in research is constantly evolving. This underscores the need for sustained resources to keep POR tools and training relevant and up-to-date. Sustaining such resources may not be feasible for all research entities. IMPLICATIONS: Collaborative approaches integrating patients in the development of POR tools ensure the content is relevant and meaningful to patients. Broader adoption of such approaches has great potential to address existing gaps and enhance the Canadian POR landscape.

OBJECTIF DU PROGRAM: L'intérêt croissant pour les initiatives de recherche axée sur le patient met en évidence le besoin de sensibiliser les chercheurs et d'offrir une formation pertinente sur les façons d'impliquer les patients comme partenaires dans les équipes de recherche. SOURCES: Dans le cadre de son mandat consistant à élaborer des documents de formation appropriés, le réseau dédié à l'avancement de la recherche en santé rénale axée sur le patient, le réseau CAN-SOLVE CKD (Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease), a créé un Comité de formation et de mentorat (CFM). MÉTHODOLOGIE: Le CFM réunit une combinaison unique de patients partenaires autochtones et non autochtones (incluant soignants, membres des familles, donneurs vivants), des chercheurs et des experts de l'application des connaissances et de l'implication des patients à la recherche, ce qui permet de conjuguer une multitude de points de vue et d'expertises. Après une évaluation des besoins en formation dans le réseau, le CFM a entrepris l'élaboration conjointe de cinq modules d'apprentissage pour combler les lacunes mises en évidence. Le comité s'est ensuite divisé en groupes de travail chargés d'en élaborer les contenus par le biais d'une approche consultative et itérative guidée par le cadre de perfectionnement DoTTI pour la création d'outils Web destinés aux patients. De plus, le CFM a intégré les principes directeurs d'inclusion, de soutien, de respect mutuel et de co-création énoncés dans le Cadre d'engagement des patients de la stratégie de recherche axée sur le patient (RAP) des Instituts de recherche en santé du Canada. PRINCIPAUX RÉSULTATS: Les cinq nouveaux modules sont: une trousse d'outils sur l'implication des patients, le partage de récits qui ont un impact, la promotion de la recherche dans le domaine rénal au Canada (KidneyPRO -Promoting Kidney Research in Canada), le cheminement d'apprentissage Wabishki Bizhiko Skaanj et l'application des connaissances. L'approche adoptée par le CFM pour développer ces modules a montré comment un groupe diversifié d'intervenants qui travaille ensemble peut mener à la création d'outils pour soutenir une RAP d'excellente qualité. Ces travaux ont également fourni une feuille de route pour d'autres entités de recherche en santé qui souhaiteraient élaborer des outils similaires dans leurs domaines respectifs. LIMITES: L'implication des patients dans la recherche est en constante évolution. Cette étude souligne le besoin de ressources durables pour garder les outils et les formations en RAP pertinents et à jour. Le maintien de telles ressources pourrait ne pas être possible pour toutes les entités de recherche. IMPLICATIONS: Les approches collaboratives qui impliquent les patients dans le développement d'outils de RAP garantissent que les contenus soient pertinents et significatifs pour les patients. L'adoption à plus grande échelle de telles approches a le potentiel de combler les lacunes existantes et d'améliorer le domaine de la RAP au Canada.

Antenatally Diagnosed Kidney Anomalies.

Congenital anomalies of the kidney and urinary tract encompass a broad spectrum of developmental conditions that together account for the majority of childhood chronic kidney diseases. Kidney abnormalities are the most commonly diagnosed congenital anomaly in children, and detection of this anomaly is increasing as a result of improved antenatal care and widespread access to more sensitive screening ultrasonography. Most paediatricians will encounter children with congenital kidney anomalies across a wide spectrum of disorders, and a broad understanding of the classification, investigation, and basis of management is important to appropriately direct their care.

Heterogeneity of Diabetes: ß-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases.

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Heterogeneity of Diabetes: ß-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases.

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Heterogeneity of Diabetes: ß-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases.

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Heterogeneity of Diabetes: ß-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases.

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Training Programs for Fundamental and Clinician-Scientists: Balanced Outcomes for Graduates by Gender.

BACKGROUND: Women scientists are less likely to obtain Assistant Professorship and achieve promotion, and obtain less grant funding than men. Scientist/clinician-scientist training programs which provide salary awards as well as training and mentorship are a potential intervention to improve outcomes among women scientists. We hypothesized whether a programmatic approach to scientist/clinician-scientist training is associated with improved outcomes for women scientists in Canada when compared with salary awards alone. Trainees within the Kidney Research Scientist Core Education and National Training Program (KRESCENT), Canadian Child Health Clinician Scientist Program (CCHCSP), and the Canadian Institutes of Health Research (CIHR) salary award programs were evaluated. OBJECTIVE: To examine whether the structured KRESCENT training program with salary support improves academic success for women scientists relative to salary awards alone. DESIGN: Retrospective cohort study. SETTING: Canadian national research scientist and clinician-scientist training programs and salary awards. PARTICIPANTS: KRESCENT cohort (n = 59, 2005-2017), CCHCSP cohort (n = 58, 2002-2015), and CIHR (n = 571, 2005-2015) Salary Awardees for postdoctoral fellows (PDF) and new investigators (NI). MEASUREMENTS: National operating grant funding success, achieving an academic position as an Assistant Professor for PDF, or achieving promotion to Associate Professor for NI. METHODS: The gender distribution of each cohort was determined using first name and NamepediA and was examined for PDF and NI, followed by a description of trainee outcomes by gender and training level. RESULTS: KRESCENT and CIHR PDF were balanced (12/27, 44% men and 55/116, 47% women) while CCHCSP had a higher proportion of women (13/20, 65%). KRESCENT and CCHCSP NI retained women scientists (19/32, 59% and 22/38, 58% women), whereas CIHR NI had fewer women (165/455, 36% women vs 290/455, 64% men, P = 0.01). There was a high rate of NI operating grant success (91%-95%) with no gender differences in each cohort. There was a high proportion of CCHCSP PDF who achieved an Assistant Professorship (18/20, 90%) that may be due in part to a longer follow-up period (9.3 ± 3 years) compared with KRESCENT PDF (7/27, 26%, 0.88 ± 4.5 years), and these data were not available for CIHR PDF. Women KRESCENT NI showed increased promotion to Associate Professor (P = 0.02, 0.25 ± 3.2 years follow-up) and CCHCSP NI had high promotion rates (37/38, 97%, 6.9 ± 3.6 years follow-up) irrespective of gender. There was an overall trend toward more men pursuing biomedical research. LIMITATIONS: KRESCENT and CCHCSP training program cohort size and heterogeneity; assigning gender by first name may result in misclassification; lack of data on the respective applicant pools; and inability to examine intersectionality with gender, ethnicity, and sexual orientation. CONCLUSION: Overall trainee performance across programs is remarkable by community standards regardless of gender. KRESCENT and CCHCSP training programs demonstrated balanced success in their PDF and NI, whereas the CIHR awardees had reduced representation of women scientists from PDF to NI. This exploratory study highlights the utility of programmatic training approaches like the KRESCENT program as potential tools to support and retain women scientists in the academic pipeline during the challenging PDF to NI transition period.

CONTEXTE: Les chercheuses sont moins susceptibles que les hommes d'obtenir une promotion ou un poste de professeur adjoint, en plus d'obtenir moins de subventions. Des programmes de formation pour les chercheurs et chercheurs cliniciens offrant des bourses salariales ainsi que de la formation et du mentorat pourraient s'avérer pertinents pour améliorer la situation des femmes en sciences. Nous avons émis l'hypothèse qu'une approche programmatique de la formation des chercheurs et chercheurs cliniciens pourrait améliorer les résultats pour les chercheuses canadiennes comparativement aux bourses salariales seules. Pour ce faire, les stagiaires du Programme national de formation scientifique et d'encadrement des chercheurs spécialisés dans le domaine rénal (KRESCENT), du Programme canadien des cliniciens-chercheurs en santé de l'enfant (PCCCSE) et des programmes de bourses salariales des Instituts de recherche en santé du Canada (IRSC) ont été évalués. OBJECTIFS: Vérifier si le programme de formation structuré KRESCENT avec soutien salarial favorise le succès académique des scientifiques féminines par rapport aux bourses salariales uniquement. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Programmes nationaux de formation et de bourses salariales pour les chercheurs et les chercheurs cliniciens du Canada. SUJETS: La cohorte KRESCENT (n = 59; 2005-2017), la cohorte PCCCSE (n = 58; 2002-2015) et les récipiendaires d'une bourse salariale des IRSC (n = 571; 2005-2015) destinées aux boursiers postdoctoraux (BPD) et aux nouveaux chercheurs (NC). MESURES: Le succès du financement des subventions de fonctionnement nationales, l'obtention d'un poste de professeur adjoint à l'université pour les BPD ou l'obtention d'une promotion au poste de professeur agrégé pour les NC. MÉTHODOLOGIE: La répartition des genres dans chaque cohorte a été déterminée à l'aide du prénom et de Namepedia, et a été examinée en fonction du statut (BPD ou NC). Les résultats des stagiaires ont été décrits selon le genre et le niveau de formation. RÉSULTATS: Dans le cas des BPD, les cohortes KRESCENT et IRSC étaient plutôt équilibrées (44 % d'hommes [12/27] pour KRESCENT et 47 % [55/116] de femmes pour IRSC). Les femmes BPD étaient plus nombreuses dans la cohorte PCCCSE (13/20 [65 %]). Du côté des NC, les femmes étaient majoritaires dans les cohortes KRESCENT et PCCCSE (respectivement 59 % [19/32] et 58 % [22/38] de femmes) et les hommes étaient plus nombreux dans la cohorte IRSC (64 % d'hommes [290/455]; 36 % de femmes [165/455] [p = 0,01]). Nous avons observé un taux élevé de réussite des subventions de fonctionnement chez les NC (91 à 95 %) dans toutes les cohortes, sans égard au genre. Une forte proportion de BPD du PCCCSE avaient obtenu un poste de professeur adjoint (18/20 [90 %]); ceci pourrait s'expliquer en partie par le plus long suivi (9,3 ± 3 ans) comparativement aux BPD du KRESCENT (7/27 [26 %]; 0,88 ± 4,5 ans). Ces données n'étaient pas disponibles pour les BPD des IRSC. On a vu une augmentation des promotions à des postes de professeurs agrégés pour les nouvelles chercheuses de la cohorte KRESCENT (p = 0,02, pour 0,25 ± 3,2 ans de suivi). Les NC du PCCCSE présentaient un taux élevé de promotions (37/38 [97 %]; 6,9 ± 3,6 ans de suivi), indépendamment du genre. Une tendance globale pour un plus grand nombre d'hommes poursuivant des recherches biomédicales a été observée. LIMITES: Parmi les limites, on compte la taille et l'hétérogénéité des cohortes KRESCENT et PCCCSE; de possibles erreurs de classification dues à l'attribution du genre par le prénom; le manque de données sur les bassins respectifs de candidats; l'incapacité d'examiner l'intersectionnalité avec le genre, l'origine ethnique et l'orientation sexuelle. CONCLUSION: Le rendement global des stagiaires dans l'ensemble des programmes est remarquable, quel que soit leur genre, par rapport aux normes communautaires. Les programmes de formation de KRESCENT et PCCCSE ont démontré un succès équilibré chez leurs BPD et NC, tandis que les récipiendaires d'une bourse des IRSC ont montré une plus faible représentation de chercheuses tant chez les BPD et les NC. Cette étude exploratoire met en lumière la pertinence d'approches de formation programmatique comme le KRESCENT pour soutenir et retenir les scientifiques féminines dans le domaine académique pendant la difficile période de transition entre le statut de boursière postdoctorale et celui de nouvelle chercheuse.

Reducing Unnecessary Imaging in Children With Multicystic Dysplastic Kidney or Solitary Kidney.

BACKGROUND AND OBJECTIVES: Children with isolated unilateral multicystic dysplastic kidney (MCDK) or congenital solitary kidney (CSK) undergo serial renal ultrasonography with variable frequency until they are transitioned to adult care. A growing body of literature suggests the value of frequent ultrasonography in this population is limited, providing no benefit to overall outcomes. Despite emerging evidence, ultrasound remains overused, resulting in avoidable health care expenditures and unnecessary use of resources. With our initiative, we aimed to improve quality of care by reducing avoidable ultrasounds in these children. METHODS: This was a single-center, prospective, interrupted time series of children <18 years with ultrasound-confirmed isolated unilateral MCDK or CSK in the outpatient nephrology clinic to evaluate the effect of a decision-making algorithm on the proportion of children receiving an avoidable ultrasound. An algorithm depicting a consensus, evidence-based protocol for managing pediatric MCDK or CSK was refined through content expert feedback and usability testing to standardize frequency of ultrasonography. Ultrasounds were deemed necessary after birth, at 6 months, and at 2, 5, 10, and 15 years. Differences pre- and postintervention were determined by using a U chart and t and F tests for significance. RESULTS: The algorithm resulted in a 47% reduction (P < .001) in the proportion of avoidable ultrasounds ordered in children with MCDK and CSK. This reduction was sustainable over a 6-month period and would result in at least $46 000 annual savings. CONCLUSIONS: Introduction of a clinical decision-making algorithm was associated with a reduction in avoidable ultrasound testing. Improving adherence across providers may allow for an even more pronounced reduction.

Transforming growth factor beta signaling functions during mammalian kidney development.

Aberrant transforming growth factor beta (TGFß) signaling during embryogenesis is implicated in severe congenital abnormalities, including kidney malformations. However, the molecular mechanisms that underlie congenital kidney malformations related to TGFß signaling remain poorly understood. Here, we review current understanding of the lineage-specific roles of TGFß signaling during kidney development and how dysregulation of TGFß signaling contributes to the pathogenesis of kidney malformation.

A Framework to Ensure Patient Partners Have Equal and Contributing Voices Throughout the Research Program Evaluation Process.

PURPOSE OF PROGRAM: Traditionally, peer review was a closed process conducted only by individuals working in the research field. To establish a more integrated and patient-centered approach, one of Canada's largest kidney research networks (Can-SOLVE CKD) has created a Research Operations Committee (ROC) that includes patients as key members. The ROC represents one way for achieving meaningful patient-oriented research (POR). SOURCE OF INFORMATION: Can-SOLVE CKD, a network created as part of the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR). METHODS: The ROC consists of patients, physicians, scientists, Indigenous partners, experts in research methodology, and a member of Can-SOLVE CKD's operational team. On an annual basis, Can-SOLVE CKD's research teams provide the ROC with a review package, which incorporates information from patient engagement check-in calls and surveys, the project's knowledge translation plan and products, and a progress report written by the project team. The ROC evaluates the review package and provides feedback and recommendations accordingly. KEY FINDINGS: The transparent nature of the process, regular feedback and review, along with an overt accountability and scoring system, has been embraced by both patients and researchers. As a result of the ROC process, the number of patient leads for each project has grown over a 3-year period and more researchers have received POR and cultural sensitivity training. LIMITATIONS: While anecdotal evidence suggests this approach is beneficial for achieving POR, formal mechanisms of evaluation are currently lacking. IMPLICATIONS: This ROC framework ensures patients are active contributors throughout the research process and could be adopted by other organizations to achieve a more patient-centered approach to research.

OBJECTIF DU PROGRAM: L'évaluation par les pairs consiste habituellement en un processus fermé et mené uniquement par des personnes travaillant dans le domaine de la recherche. Pour développer une approche plus intégrée et davantage axée sur les patients, un des plus importants réseaux canadiens de recherche sur les maladies rénales (Can-SOLVE CKD) a créé un comité de gestion de la recherche (CGR) où les patients sont des membres à part entière. Une approche qui vise la conduite d'activités de recherches significatives et davantage orientées vers le patient. SOURCE: Can-SOLVE CKD, un réseau créé dans le cadre de la Stratégie de recherche axée sur le patient (SRAP) des Instituts de recherche en santé du Canada (IRSC). MÉTHODOLOGIE: Le CGR rassemble des patients, des médecins, des chercheurs, des partenaires autochtones, des experts en méthodologie de recherche et un membre de l'équipe d'intervention de Can-SOLVE CKD. Une fois par année, l'équipe de recherche de Can-SOLVE CKD fournit au CGR un dossier d'examen. Ce dossier contient les informations recueillies lors d'appels ou de sondages vérifiant l'engagement des patients, le plan d'application des connaissances du projet et ses résultats, de même qu'un rapport périodique rédigé par l'équipe responsable du projet. Le CGR évalue ce dossier et émet ses commentaires et recommandations. PRINCIPAUX RÉSULTATS: La transparence du processus, la rétroaction et la révision sur une base régulière, de même que les systèmes de responsabilité et de notation ouverts ont été adoptés tant par les patients que par les chercheurs. Grâce à ce processus, le nombre de patients candidats pour chaque projet a augmenté sur une période de trois ans, et davantage de chercheurs ont reçu une formation sur les réalités culturelles et la pratique d'activités de recherche axées sur le patient. LIMITES: Bien que des preuves anecdotiques suggèrent que cette approche soit bénéfique à la conduite de recherches axées sur le patient, des mécanismes formels pour son évaluation manquent toujours. CONCLUSION: Le cadre proposé par le CGR assure une contribution active des patients tout au long du processus de recherche. Ce program pourrait être adopté par d'autres organizations et permettre la réalisation d'activités de recherche davantage axées sur le patient.

COVID-19: a pandemic experience that illuminates potential reforms to health research.

COVID-19 has halted research around the globe and forced researchers out of their laboratories. Non-emergency medical appointments were canceled. Ongoing clinical trials were challenged to create new modes of operation while public pressure mounted to find therapeutic options against COVID-19. Yet, the inability to conduct research during COVID-19 was overcome with cooperation, resource sharing, and compassion, which provides important lessons on how to improve health related research as we enter a new normal.