Offspring from mothers with diabetes mellitus are at risk of altered calcium homeostasis. Using the streptozotocin rat model of diabetic pregnancy, we have previously shown that diabetic mothers show marked hypercalciuria (Birdsey et al. 1995). We have also shown that the adult offspring of these rats have, by contrast, reduced urinary calcium output (Hamilton et al. 1999; Bond et al. 2002). Furthermore, increased calbindin-D28K and plasma membrane calcium-ATPase (PMCA) protein expression in kidneys of diabetic rat offspring has also been observed (Bond et al. 2002, 2003). The aim of this study was to establish whether these changes in renal function are apparent in younger animals.
Two rat groups were studied; offspring born to control mothers (OC) and offspring born to streptozotocin-induced diabetic mothers (OD). All rats were fostered at birth to a separate group of control dams. Servo-controlled renal clearance techniques were performed on anaesthetised (Intraval 100 mg kg-1) OD and OC at 4 and 8 weeks of age. Urine samples were taken every 15 min, blood samples every hour and glomerular filtration rate was determined by [3H]inulin clearance. Urinary calcium was measured using atomic absorption spectrophotometry. Animals were humanely killed at the end of the experiment.
Both GFR and UV were significantly higher in 4 week (P < 0.05) and 8 week (P < 0.01) OD. No difference in calcium excretion was observed at 4 weeks but there was a significant increase (P < 0.01) in UCaV in OD relative to OC at 8 weeks. However, FECa was significantly lower (P < 0.01) in OD from both groups.
These data show that altered renal calcium handling is apparent in rats born to diabetic mothers from the age of 4 weeks. The decreased fractional excretion of calcium in OD supports previous observations of increased renal calcium transport proteins in offspring born to diabetic mothers.
This work was supported by the North West Kidney Research Association.
