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Preterm neonates are exposed at birth to high oxygen concentrations relative to the intrauterine environment. We have previously shown in a rat model that a hyperoxic insult results in a reduced nephron number in adulthood. Therefore, the aim of this study was to determine the effects of transient neonatal hyperoxia exposure on nephrogenesis. Sprague-Dawley rat pups were raised in 80% O2 or room air from P3 to P10. Pups (n = 12/group, 6 males and 6 females) were sacrificed at P5 (during active nephrogenesis) and at P10 (after the completion of nephrogenesis). Hyperoxia exposure resulted in a significant reduction in both nephrogenic zone width and glomerular diameter at P5, and a significantly increased apoptotic cell count; however, nephron number at P10 was not affected. HIF-1α expression in the developing kidney was significantly reduced following hyperoxia exposure. Systemic administration of the HIF-1α stabilizer dimethyloxalylglycine (DMOG) resulted in enhanced expression of HIF-1α and improved nephrogenesis: kidneys from hyperoxia-exposed pups treated with DMOG exhibited a nephrogenic zone width and glomerular diameter similar to room-air controls. These findings demonstrate that neonatal hyperoxia exposure results in impaired nephrogenesis, which may be at least in part HIF-1α-mediated. Although nephron number was not significantly reduced at the completion of nephrogenesis, early indicators of maldevelopment suggest the potential for accelerated nephron loss in adulthood. Overall, this study supports the premise that prematurely born neonates exposed to high oxygen levels after birth are vulnerable to impaired renal development.

Background: We report on the proceedings of a national workshop held in Canada with the aims to identify priorities for research in childhood nephrotic syndrome and to develop a national strategy to address these priorities. Methods: A diverse group of participants attended the meeting, including patients, family members, researchers, and health care providers. We used small group discussions to explore priorities as perceived by patients and families and by health care providers and researchers. Results: Research evaluating glucocorticoid minimization or glucocorticoid-sparing regimens was a consistent theme in the patient and family discussion group. Families also indicated the need for precise prognostic information at diagnosis, more information to help them choose the best available therapy, and more resources for disease management. Health care providers emphasized the importance of better disease characterization including genotyping and phenotyping patients, better understanding the pathogenesis, and the need of providing targeted therapy and precise prognostic information. Conclusions: These priorities will inform the development and future directions of the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project, a national research initiative to improve care and outcomes of patients with childhood onset nephrotic syndrome.

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.