Development of cardiovascular disease due to renal insufficiency in male sheep following fetal unilateral nephrectomy

Singh, Reetu R., Denton, Kate M., Bertram, John F., Jefferies, Andrew J., Head, Geoffrey A., Lombardo, Paul, Schneider-Kolsky, Michal and Moritz, Karen M. (2009) Development of cardiovascular disease due to renal insufficiency in male sheep following fetal unilateral nephrectomy. Journal of Hypertension, 27 2: 386-396. doi:10.1097/HJH.0b013e32831bc778


Author Singh, Reetu R.
Denton, Kate M.
Bertram, John F.
Jefferies, Andrew J.
Head, Geoffrey A.
Lombardo, Paul
Schneider-Kolsky, Michal
Moritz, Karen M.
Title Development of cardiovascular disease due to renal insufficiency in male sheep following fetal unilateral nephrectomy
Journal name Journal of Hypertension   Check publisher's open access policy
ISSN 0263-6352
Publication date 2009-02
Year available 2009
Sub-type Article (original research)
DOI 10.1097/HJH.0b013e32831bc778
Volume 27
Issue 2
Start page 386
End page 396
Total pages 11
Editor A. Zanchetti
G. Mancia
P. Daly
Place of publication United Kingdom
Publisher Lippincott Williams & Wilkins, Ltd.
Language eng
Subject C1
111603 Systems Physiology
110201 Cardiology (incl. Cardiovascular Diseases)
110312 Nephrology and Urology
111401 Foetal Development and Medicine
920501 Child Health
Formatted abstract
AB Background:
Renal insufficiency is associated with the development of cardiovascular disease.

Objectives:
This study investigated whether reduced fetal renal mass resulted in renal insufficiency, hypertension, cardiac dysfunction and whether these changes progressed with age.

Methods and results:

Fetal uninephrectomy was performed at 100-day gestation (term, 150 days) and studies performed in male sheep from 6 weeks to 24 months of age. Renal function declined with age in sham animals as demonstrated by increasing plasma creatinine levels and urinary excretion of albumin. The age-related decline in renal function was exacerbated in animals that had undergone fetal uninephrectomy. Evidence of renal insufficiency was indicated from as early as 6 weeks of age with elevations in plasma creatinine (Ptreatment < 0.001), urea (Ptreatment < 0.001) and sodium (Ptreatment < 0.05) levels in uninephrectomized lambs as compared with sham animals. At 6 months, urinary albumin excretion (P < 0.001) was increased and urinary sodium excretion (P < 0.001) decreased in the uninephrectomized animals. By 24 months, renal function had deteriorated further with significant progression of albuminuria (Ptreatmentxage < 0.001). Elevation of mean arterial pressure (~15 mmHg) was associated with significantly increased cardiac output, stroke volume and plasma volume at 6 months; arterial pressure (~27 mmHg) had increased further in uninephrectomized animals at 24 months and was driven by increased total peripheral resistance. Cardiac functional reserve (dobutamine challenge) was reduced in uninephrectomized animals at 6 and 24 months of age (Ptreatment < 0.001), and this was associated with left ventricular enlargement (P < 0.001) and reduced fractional shortening (P < 0.01).

Conclusion:

Fetal uninephrectomy causing a reduction in nephron endowment results in an accelerated age-related decline in renal function. This is associated with an early onset of elevated blood pressure and impairments in cardiac structure and function. (C) 2009 Lippincott Williams & Wilkins, Inc.
Keyword Cardiovascular
Dobutamine
Hypertension
Nephron number
Renal
Uninephrectomy
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 01 Sep 2009, 14:22:15 EST by Cameron Harris on behalf of School of Biomedical Sciences