NDT Advance Access published online on November 30, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh579
© 2004 by European Renal Association - European Dialysis and Transplant Association
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Nephrology, Groningen University Medical Center, Groningen, The Netherlands; These authors contributed equally to this work
* To whom correspondence should be addressed. Background. In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. Methods. Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. Results. As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial Conclusion. Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.
Accepted October 13, 2004
Original Articles
Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage
2 Department of Nephrology, Groningen University Medical Center, Groningen, The Netherlands; Department of Pathology and Laboratory Medicine, Groningen University Medical Center, Groningen, The Netherlands
3 Department of Pathology and Laboratory Medicine, Groningen University Medical Center, Groningen, The Netherlands
4 Department of Nephrology, Groningen University Medical Center, Groningen, The Netherlands
Gerjan Navis, E-mail: g.j.navis{at}int.azg.nl
Abstract 
-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular -smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Ochodnicky, R. H. Henning, H. Buikema, A. C. A. Kluppel, M. van Wattum, D. de Zeeuw, and R. P. E. van Dokkum Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage Nephrol. Dial. Transplant., February 1, 2009; 24(2): 413 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hamming, H. van Goor, A. J. Turner, C. A. Rushworth, A. A. Michaud, P. Corvol, and G. Navis Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats Exp Physiol, May 1, 2008; 93(5): 631 - 638. [Abstract] [Full Text] [PDF]
|
|