Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein dietin utero

Abstract

Intrauterine growth retardation associated with maternal undernutrition is proposed to play a significant role in the aetiology of hypertension and CHD. Animal experiments suggest that the kidney, which is extremely vulnerable to the adverse effects of growth-retarding factors, may play an important role in the prenatal programming of hypertension. Maintenance of renal haemodynamic functions following structural impairment in fetal life is proposed 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 clearance, blood urea N, plasma and urinary albumin, renal morphometry and metabolic activity at 4, 12 and 20 weeks of age. Blood pressure was elevated at all 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 were shorter and wider than those of control animals. Creatinine clearance was significantly reduced in 4-week-old rats exposed to the low-protein diet. Renal morphometry and creatinine clearance at older ages were not influenced by prenatal diet. Blood urea N, urinary output and urinary albumin excretion were, however, significantly greater in low-protein-exposed rats than in control rats at 20 weeks of age. These findings are suggestive of a progressive deterioration of renal function in hypertensive rats exposed to mild maternal protein restriction during fetal life. This is consistent with the hypothesis that adaptations to maintain renal haemodynamic functions following impairment of fetal nephrogenesis result in an accelerated progression towards glomerulosclerosis and increased intrarenal pressures mediated by rising vascular resistance.