Intrauterine growth retardation leads to a permanent nephron deficit in the rat

Abstract

Intrauterine growth retardation (IUGR) was induced in Sprague-Dawley rats by partial artery ligation of one uterine horn in the mother on day 17 of gestation or by feeding the mother a 5% protein diet from day 8 of gestation. The controls were pups of the contralateral uterine horn or pups born to mothers fed a normal (22%) protein diet. The number of nephrons present at birth and the final number of nephrons in 2-week-old rats were counted throughout the entire kidney. The number of nephrons present at birth and the final number of nephrons were significantly correlated with birth weight for growth-retarded rats of both groups and their corresponding controls (P < 0.02 for the poorest correlation). Clearance experiments and morphometric studies of 2-week-old rats born to mothers with uterine artery ligation indicated that, despite a large compensatory hypertrophy of the nephrons in those animals born with a nephron deficit of about 30%, the overall renal function was impaired. We conclude that IUGR is accompanied by a nephron deficit which may not be fully compensated for within the first weeks after birth.

The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis

“…In small, long-term studies of individuals of low birthweight, glomerular filtration rate and UAER are normal in early adulthood [27,28]. Many previous studies have described changes in glomerular volume [23,29,30] secondary to a reduction in glomerular number produced by a variety of causes. However, a detailed systematic analysis of kidney morphology in low birthweight animals has not been described previously.…”

“…Animals of low birthweight (LBW) induced by protein deprivation in utero have smaller kidneys with lower numbers of glomeruli than animals of normal birthweight (NBW) [3,4]. Although some compensatory hypertrophy of the remaining nephrons occurs, it is likely that the total glomerular filtration surface area remains low.…”

A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products

“…Similarly, maternal protein restriction during pregnancy in rats results in offspring with low birth weight offspring and reduced kidney size and nephron endowment [3][4][5]. It has been postulated that a reduction in nephron endowment acts as a primary renal insult on the kidney, whereby compensatory mechanisms are initiated to maintain normal renal function [6].…”

Nephron Endowment and Filtration Surface Area in the Kidney after Growth Restriction of Fetal Sheep

“…A number of experimental and human studies have demonstrated reduced nephron endowment as a result of IUGR, suggesting that a compromised in utero environment impairs nephrogenesis (1)(2)(3). A reduction in nephron number at birth could have long-lasting effects on renal function.…”