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Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats

¹UPRES EA 2193, Faculté de Médecine, Université de la Méditerranée, Marseille; ²Division of Neonatology, Hôpital la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille; ³UPRES EA 3281, Faculté de Médecine, Université de la Méditerranée, Marseille; and ⁴Centre de Recherche U652, Institut Biomédical des Cordeliers, Paris, France

Submitted 27 March 2007 ; accepted in final form 19 September 2007

Various antenatal events impair nephrogenesis in humans as well as in several animal models. The consecutive low nephron endowment may contribute to an increased risk for cardiovascular and renal diseases in adulthood. However, little knowledge is available on the influence of the postnatal environment, especially nutrition, on nephrogenesis. Moreover, the consequences of early postnatal nutrition in late adulthood are not clear. We used a model of early postnatal overfeeding (OF) induced by reduction of litter size (3 pups/litter) in rats. Systolic blood pressure (SBP; plethysmography), glomerular filtration rate (clearance of creatinine), glomerular number and volume, and glomerulosclerosis were evaluated in 22-mo-old aging offspring. Early postnatal OF was associated with increased weight gain during the suckling period (+40%, P < 0.01) and a 20% increase in glomerular number (P < 0.05). However, an increase in SBP at 12 mo by an average of 18 mmHg and an increase in proteinuria (2.6-fold) and glomerulosclerosis at 22 mo of age were observed in OF male offspring compared with controls. In conclusion, early postnatal OF in the rat enhances postnatal nephrogenesis, but elevated blood pressure and glomerulosclerosis are still observed in male adults. Factors other than glomerular number reduction are likely to contribute to the arterial hypertension induced by early postnatal OF.

nephrogenesis; glomerular number; overfeeding; arterial blood pressure; infant; newborn; developmental origins of adult diseases

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