Adverse effects of hyperglycemia on kidney development in rats - In vivo and in vitro studies

Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adve rse effects of hyperglycemia on kidney development in the rat, Female rats were made hyperglycemic throughout gestation with a single injection of str eptozotocin (STZ) on day 0 of gestation, or for a short period encompassing the early stage of renal organogenesis by infusing glucose from gestationa l days 12-16. Kidney development in the pups was assessed by determining th e total number of nephrons formed in the kidney. The number of nephrons was significantly reduced (10-35%) in the pups from STZ-treated dame, as a fun ction of hyperglycemia. There were also fewer nephrons in pups from dams gi ven glucose infusion whose hyperglycemia was transiently higher on day 13 o f gestation. The in vitro experiments were done on metanephroi removed from 14-day-old fetuses and grown for 6 days in medium containing 0, 6.9, 13.8, or 27.5 mmol/l glucose. The development of explants grown in 0, 13.8, and 27.5 mmol/l glucose was impaired compared with that of explants grown in th e 6.9 mmol/l control medium, showing that the glucose concentration must be closely controlled to ensure optimum in vitro metanephros development. Thu s, exposure to hyperglycemia in utero can cause a nephron deficit, which in turn may have renal consequences later in life.