Evidence of progressive deterioration of renal function in rats exposed toa maternal low-protein diet in utero

Intrauterine growth retardation associated with maternal undernutrition is proposed to play a significant role in the aetiology of hypertension and CH D. Animal experiments suggest that the kidney, which is extremely vulnerabl e to the adverse effects of growth-retarding factors, may play an important role in the prenatal programming of hypertension. Maintenance of renal hae modynamic functions following structural impairment in fetal life is propos ed to require adaptations which raise systemic blood pressure and promote a more rapid progression to renal failure. Rats were fed on diets containing 180 g casein/kg (control) or 90 g casein/kg (low protein) during pregnancy . The offspring were studied in terms of blood pressure, creatinine clearan ce, blood urea N, plasma and urinary albumin, renal morphometry and metabol ic activity at 4, 12 and 20 weeks of age. Blood pressure was elevated at al l ages in the low-protein-exposed offspring, relative to control rats. Rats (4 weeks old) exposed to the low-protein diet had smaller kidneys which we re shorter and wider than those of control animals. Creatinine clearance wa s significantly reduced in 4-week-old rats exposed to the low-protein diet. Renal morphometry and creatinine clearance at older ages were not influenc ed by prenatal diet. Blood urea N, urinary output and urinary albumin excre tion were, however, significantly greater in low-protein-exposed rats than in control rats at 20 weeks of age. These findings are suggestive of a prog ressive deterioration of renal function in hypertensive rats exposed to mil d maternal protein restriction during fetal life. This is consistent with t he hypothesis that adaptations to maintain renal haemodynamic functions Fol lowing impairment of fetal nephrogenesis result in an accelerated progressi on towards glomerulosclerosis and increased intrarenal pressures mediated b y rising vascular resistance.