Postnatal food restriction in the rat as a model for a low nephron endowment

Abstract

A low nephron endowment may be associated with hypertension. Nephrogenesis is the process that leads to the formation of nephrons until week 36 of gestation in humans and may be inhibited by many factors like intrauterine growth restriction and premature birth. To study the consequences of a low glomerular number, animal models have been developed. We describe a model of postnatal food restriction in the rat in which litter size is increased to 20 pups, which leads to growth restriction. In the rat, active nephrogenesis continues until postnatal day 8, which coincides with the growth restriction in our model. Design-based stereological methods were used to estimate glomerular number and volume. Our results show an approximately 25% lower glomerular number in rats after postnatal food restriction (30,800 glomeruli/kidney) compared with control rats (39,600 glomeruli/kidney, P < 0.001). Mean glomerular volume was increased by 35% in the growth-restricted rats (P = 0.006). There was a significant negative correlation between glomerular volume and glomerular number (r = -0.76, P < 0.001). We conclude that postnatal food restriction in the rat leads to a low nephron endowment with compensatory enlargement. It is therefore a suitable model to study the effect of intrauterine growth restriction or prematurity on kidney development and the consequences of a reduced glomerular number in later life.