Genetic Disorders – Development

Kidney International (2005) 67, 822–828; doi:10.1111/j.1523-1755.2005.00147.x

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

KAREN M MORITZ, ANDREW JEFFERIES, JAMES WONG, E MARELYN WINTOUR and MIODRAG DODIC

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia; Department of Anatomy and Cell Biology, Monash University, Clayton, Victoria, Australia; Department of Physiology, Monash University, Clayton, Victoria, Austalia; and Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia

Correspondence: Dr Karen Moritz, Department of Anatomy and Cell Biology, Monash University, Clayton, 3800, Australia. E-mail:karen.moritz@med.monash.edu.au

Received 9 February 2004; Revised 23 July 2004; Accepted 22 September 2004.

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Abstract

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

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 plusminus 2 mm Hg) compared to control animals (86 plusminus 2 mm Hg) (P < 0.05). Cardiac output was significantly higher in the uninephrectomized group (148 plusminus 10 mL/kg/min) compared to the control group (124 plusminus 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.

Keywords:

cardiac output, fetal uninephrectomy, functional renal reserve

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