Early defect in branching morphogenesis of the ureteric bud in induced nephron deficit

Early defect in branching morphogenesis of the ureteric bud in induced nephron deficit. Development of the metanephric kidney during embryogenesis can be altered both in vivo and in vitro by exposure to gentamicin, which may lead to oligonephronia. To study the role of the ureteric bud in nephron deficit genesis, we used metanephros organ cultures exposed to gentamicin as a model of impaired nephrogenesis. Ultrastructural localization of the antibiotic showed that by eight hours it was already present within the epithelial cells of the ureteric bud and in its growing ends, and also trapped in the adjacent blastema. Using confocal microscopy and image analysis, we devised a quantitative approach to analyze the branching pattern of the ureteric bud, and showed that by 24 hours of culture, despite no change of explants growth, gentamicin had significantly decreased the number of branching points. This effect involved the early branching events and was limited to end buds that had no nephron anlagen nearby. Our findings indicate that impaired branching morphogenesis of the ureteric bud is the likely event of gentamicin-induced nephron deficit

The Association Between Birthweight and Current Blood Pressure: A Cross-Sectional Study in an Australian Aboriginal Community

Objectives: To study the relationship of blood pressure to birthweight and current body mass index in a population with high rates of low birthweight (< 2.5 kg). Design: A cross-sectional population screening program conducted between 1992 and 1998, with retrospective retrieval of birthweights. Setting: A remote coastal Australian Aboriginal community with a high prevalence of diabetes, cardiovascular and renal disease. Participants: Eighty-two per cent of the community members (1473/1805) were screened. Birthweights were available for 767 (71%) of the screened participants aged 7-43 years. Main outcome measures: The association between birthweight and current blood pressure, accounting for current body mass index. Results: Mean birthweights were low, and 18% of children and 35% of adults had been low-birthweight babies. In children (7-17 years), blood pressure was not correlated with birthweight, but in adults there was an inverse correlation - a 1 kg increase in birthweight was associated with a 2.9 mmHg (95% CI, 0.3-5.5 mmHg) decrease in systolic blood pressure, after adjusting for age, sex and current weight. Overweight adults with low birthweight had the highest blood pressures. Conclusions: Low birthweight is significantly associated with higher blood pressure in adult life, and the effect is amplified by higher current weight. Given the high rates of low birthweight in Aboriginal people in remote areas, and the detrimental effect of higher blood pressures on chronic diseases (currently present in epidemic proportions), interventions should focus on improving birthweights and on weight control in adolescents and adults. Special attention should be paid to children with low birthweight to avoid their becoming overweight in adult life