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

Moritz KM, Jefferies A, Wong J, Wintour EM, Dodic M

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia. karen.moritz@med.monash.edu.au

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.

Published 8 February 2005 in Kidney Int, 67(3): 822-8.
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