Fetal programming of renal morphology and function

Abstract

Previous epidemiological evidence from a number of studies supports the hypothesis that the risk of essential hypertension, coronary heart disease and non-insulin dependent diabetes is, in part, programmed by intrauterine nutritional status. An increasing number of human studies indicate that the developing kidney is particularly vulnerable to the adverse effects of fetal growth retarding influences. In animals growth retarding diets or other insults, which have an impact on the development of cardiovascular functions, also appear to impact upon nephron number. In this study, the feeding of a 9% casein diet to pregnant rats, a mild protein restriction, reduced nephron number in the offspring, which progressively declined with age compared to those exposed to an 1 8% control diet. At weaning low-protein exposed offspring had hypertension and evi(leflCC of renal insufficiency. On natural death, the kidneys from aged male rats exposed to both low-protein and control maternal diets had a higher incidence glornerulosclerosis and renal disruption than females. Supplementing the maternal 9% casein diet with 3% glycine, 1.5% urea and 3% alanine in the rat normalised nephron number in the offspring. Only the addition of glycinc in the maternal low- protein diet prevented the appearance of high blood pressure in the offspring. In this study it has been demonstrated that in humans, those of a low birth weight or ponderal index, a marker of fetal undernutrition, had evidence of increased glomerular permeability, but not elevated blood pressure at age 10. This association was not evident at age 12 or in a separate cohort of young adults. It is possible that hypertension and a reduced nephron reserve are not causally associated. The evidence from this thesis suggest that prenatal undernutrition may programme renal structure in later life, but that renal programming is not one of the primary mechanisms leading to hypertension

Date of Award	2004
Original language	English
Awarding Institution	University of Northampton
Supervisor	Carol Phillips (Supervisor)