The effect of a low-protein diet in pregnancy on offspring renal calcium handling

1 Faculty of Life Sciences, University of Manchester, Manchester; 2 Division of Human Development, St Mary's Hospital, Manchester; 3 Vitamin D Research Group, Faculty of Medical and Human Sciences, Manchester Royal Infirmary, Manchester; and 4 Division of Laboratory and Regenerative Medicine, The Medical School, Manchester, United Kingdom Submitted 21 July 2006 ; accepted in final form 7 June 2007 Low birth weight humans and rats exposed to a low-protein diet in utero have reduced bone mineral content. Renal calcium loss during the period of rapid skeletal growth is associated with bone loss. Because young rats exposed to low protein display altered renal function, we tested the hypothesis that renal calcium excretion is perturbed in this model. Pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (low) protein throughout gestation. Using standard renal clearance techniques, Western blotting for renal calcium transport proteins, and assays for Na + -K + -ATPase activity and serum calcitropic hormones, we characterized calcium handling in 4-wk-old male offspring. Histomorphometric analyses of femurs revealed a reduction in trabecular bone mass in low-protein rats. Renal calcium (control vs. low protein: 10.4 ± 2.1 vs. 27.6 ± 4.5 nmol·min –1 ·100 g body wt –1 ; P < 0.01) and sodium excretion were increased, but glomerular filtration rate was reduced in low-protein animals. Total plasma calcium was reduced in low-protein rats ( P < 0.01), but ionized calcium, serum calcitropic hormone concentrations, and total body calcium did not differ. There was no significant change in plasma membrane Ca 2+ -ATPase pump, epithelial calcium channel, or calbindin-D 28K expression in low-protein rat kidneys. However, Na + -K + -ATPase activity was 36% lower ( P < 0.05) in low-protein rats. These data suggest that the hypercalciuria of low-protein rats arises through a reduction in passive calcium reabsorption in the proximal tubule rather than active distal tubule uptake. This may contribute to the reduction in bone mass observed in this model. bone; kidney; programming Address for reprint requests and other correspondence: N. Ashton, Faculty of Life Sciences, Univ. of Manchester, 1.124 Stopford Bldg., Oxford Road, Manchester M13 9PT, UK (e-mail: nick.ashton{at}manchester.ac.uk )