Fetal Uninephrectomy Leads to Postnatal Hypertension and Compromised Renal Function

Abstract

It has been proposed that the number of nephrons an individual has may be inversely related to his or her blood pressure. In this study using female ovine fetuses, nephron number was reduced by performing a fetal uninephrectomy during the period of active nephrogenesis (100 days of gestation, term=150 days). Lambs were born at term and grew at a similar rate. At 5 months of age, ovaries were removed and the carotid artery exteriorized into a fold of skin. Blood pressure and renal function were studied at 6 and 12 months of age. At 6 months of age, uninephrectomized lambs had significantly higher mean arterial blood pressure than sham-operated lambs (89±2 versus 82±2 mm Hg, P <0.05) when measured over a 3-day period. Heart rate was not different between the groups. Urine flow rate was similar, but glomerular filtration rate was significantly lower in uninephrectomized animals ( P <0.05). Urinary concentrations and excretion rates of sodium tended to be higher in uninephrectomized animals but were similar for chloride and potassium. There was no evidence of proteinuria in the uninephrectomized lambs. Similar differences were observed in blood pressure and renal function at 12 months of age. Plasma renin concentrations at this age were lower in the uninephrectomized lambs ( P <0.05). An oral salt load for 10 days did not increase blood pressure significantly in either group at 12 months of age, nor were there differences in the responsiveness to graded doses of angiotensin II. These results suggest that formation of a low nephron number in utero, may result in elevated blood pressure and compromised renal function in later life.