Suitability of 5/6 nephrectomy (5/6NX) for the induction of interstitial renal fibrosis in rats – Influence of sex, strain, and surgical procedure

Chronic renal failure (CRF) is a serious clinical problem and currently there are no adequate therapeutic strategies for treatment. Many possible treatment strategies have been tested in rats with CRF induced by subtotal nephrectomy. However, reports in the literature concerning the consequences of...

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Published in:Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2006-01, Vol.57 (3), p.195-205
Main Authors: Fleck, Christian, Appenroth, Dorothea, Jonas, Patrick, Koch, Mark, Kundt, Günther, Nizze, Horst, Stein, Günter
Format: Article
Language:English
Subjects:
5/6 nephrectomy
Animals
Biological and medical sciences
Body Weight
Chronic renal failure
Creatinine clearance
Disease Models, Animal
Female
Fibrosis - physiopathology
Fibrosis - veterinary
Glomerulonephritis - physiopathology
Glomerulonephritis - veterinary
Hydroxyproline
Investigative techniques, diagnostic techniques (general aspects)
Kidney - physiology
Kidneys
Male
Medical sciences
Morphology
Nephrectomy - veterinary
Nephrology. Urinary tract diseases
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Rats
Rats, Sprague-Dawley
Rats, Wistar
Renal fibrosis
Sex differences
Sex Factors
Sprague–Dawley rats
Urinary system involvement in other diseases. Miscellaneous
Wistar rats
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Summary:Chronic renal failure (CRF) is a serious clinical problem and currently there are no adequate therapeutic strategies for treatment. Many possible treatment strategies have been tested in rats with CRF induced by subtotal nephrectomy. However, reports in the literature concerning the consequences of this procedure on rat kidney function are contradictory. For instance, such an intervention in male Sprague–Dawley rats apparently initiates the development of interstitial renal fibrosis, while in our similar studies on female Wistar rats (HW) there was minimal renal fibrosis. Therefore, we carried out experiments in adult rats to investigate the long-term consequences of 5/6 nephrectomy (5/6NX) in relation to (1) sex, (2) strain, and (3) two methods of surgical ablation. Ten weeks after 5/6NX, body weight gain, systolic blood pressure, creatinine clearance, and urinary protein were measured, along with renal hydroxyproline concentration determinations to assess the deposition of extracellular matrix. Also, light microscopic investigations were done to characterize renal damage. The functional parameters clearly indicated the development of CRF, while morphologic investigations showed only moderate fibrotic areas containing atrophic tubules and lymphocytic infiltrates. However, 45–60% of glomeruli were sclerotic. In summary, 5/6NX, using either method of partial nephrectomy, induces signs of moderate glomerulonephritis preferentially in female HW rats. Thus 5/6NX in female HW rats can be recommended as a suitable model in the induction of renal fibrosis.
ISSN:0940-2993
1618-1433
DOI:10.1016/j.etp.2005.09.005