Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies.

Abstract

Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) on day 0 of gestation, or for a short period encompassing the early stage of renal organogenesis by infusing glucose from gestational days 12-16. Kidney development in the pups was assessed by determining the total number of nephrons formed in the kidney. The number of nephrons was significantly reduced (10-35%) in the pups from STZ-treated dams, as a function of hyperglycemia. There were also fewer nephrons in pups from dams given glucose infusion whose hyperglycemia was transiently higher on day 13 of 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 the 6.9 mmol/l control medium, showing that the glucose concentration must be closely controlled to ensure optimum in vitro metanephros development. Thus, exposure to hyperglycemia in utero can cause a nephron deficit, which in turn may have renal consequences later in life.