US EPA

1433146 

Journal Article 

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

Fleck, C; Appenroth, D; Jonas, P; Koch, M; Kundt, G; Nizze, H; Stein, G 

2006 

Yes 

Experimental and Toxicologic Pathology
ISSN: 0940-2993
EISSN: 1618-1433 

57 

3 

195-205 

16410187 

10.1016/j.etp.2005.09.005 

WOS:000235892600002 

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. (c) 2005 Elsevier GmbH. All rights reserved. 

chronic renal failure; renal fibrosis; 5/6 nephrectomy; Wistar rats; Sprague-Dawley rats; sex differences; hydroxyproline; creatinine clearance; morphology