Reduced renal reserve and increased cardiac output in adult female sheep uninephrectomized as fetuses

Abstract

Background. Removal of one kidney during the period of nephrogenesis in the sheep leads to offspring with elevated blood pressure and reduced glomerular filtration rate (GFR) at 6 and 12 months of age. The mechanisms underlying the hypertension and the degree of renal impairment are not known. Methods. Changes in GFR were measured in response to an infusion of amino acids and cardiac output was measured by thermal dilution in female offspring at 2 years of age in eight control (sham-operated) and seven animals that had been unilaterally nephrectomized at 100 days of gestation. Results. Animals uninephrectomized as fetuses had significantly higher blood pressure (91 ± 2 mm Hg) compared to control animals (86 ± 2 mm Hg) (P < 0.05). Cardiac output was significantly higher in the uninephrectomized group (148 ± 10 mL/kg/min) compared to the control group (124 ± 6 mL/kg/min) (P < 0.05). Heart rate and stroke volume were similar in the two groups although both parameters tended to be higher in the uninephrectomized group. Uninephrectomized animals had a lower basal GFR (P < 0.05). An infusion of amino acids caused a significantly different response in GFR in the two groups (P < 0.01 between the groups) with the uninephrectomized animals having significantly lower GFRs during the infusion period. Conclusion. The increased blood pressure observed after fetal uninephrectomy is due to an increase in cardiac output. Thus, formation of a low number of nephrons in utero may predispose an individual to later renal failure and elevated blood pressure. © 2005 by the International Society of Nephrology.